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Backgrounds: Research has demonstrated that elevated serum total bilirubin (STB) levels have a beneficial impact on various diseases, particularly metabolic syndrome. This study aims to investigate the association between STB levels and serum testosterone (STT) in order to determine if bilirubin plays a protective role in relation to testosterone deficiency (TD) risk. Methods: In this study, a total of 6,526 eligible male participants aged 20 years or older were analyzed, all of whom took part in the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2016. To investigate the relationship between STB and STT levels, we employed weighted multivariate regression models along with restricted cubic splines (RCS). Additionally, a subgroup analysis was conducted to explore the heterogeneity of this relationship across different subpopulations. Results: Among the participants, 1,832 individuals (28.07%) were identified as having testosterone deficiency (TD), defined as an STT level below 300 ng/dL. A significant positive correlation between STB and STT levels was observed in both crude and adjusted models (all P < 0.0001). The association between STB and STT levels was found to be statistically significant up to a threshold of 17.1 µmol/L, after which it became statistically insignificant(P for non-linearity = 0.0035). Weighted logistic regression analysis indicated that a 1 µmol/L increase in STB was associated with a 4% decrease in the likelihood of TD (odds ratio = 0.96, P < 0.0001). Subgroup analysis showed that the inverse relationship was limited to individuals aged 60 and over, non-smokers/drinkers, and obese individuals. Conclusion: STB within the physiological range(17.1 µmol/L) was positively associated with STT in adult males. The potential protective role of bilirubin regarding testosterone levels merits further exploration. [ABSTRACT FROM AUTHOR]

Cannabidiol (CBD) vape pen usage has been on the rise given the changing political and scientific climate as well as the promotion of these delivery systems as a more accessible and lower-risk option for consumers. Despite being marketed as a safer way to use cannabis, CBD vape liquids are sold without restrictions or meticulous quality control procedures such as toxicological and clinical assessment, standards for product preservation, or investigative degradation analyses. Nine CBD-labeled vape liquid samples purchased and manufactured in the United States were evaluated and assessed for cannabinoid content. Quantification and validation of cannabinoids and matrix components was accomplished using gas and liquid chromatography with mass spectrometry analysis (GC-MS and LC-MS/MS) following liquid-liquid extraction with methanol. Samples degraded by temperature (analyzed by GC-MS) showed a greater disparity from the labeled CBD content compared with samples analyzed as purchased (by LC-MS/MS). Thermal degradation of the vape liquids showed increased levels of tetrahydrocannabinol (THC). Also, extended time and temperature degradation were evaluated in vape liquids by storing them for 5 months and then varying temperature conditions before analysis, which indicated CBD transformed into other cannabinoids leading to different cannabinoid content within the vape samples. Evaluation conducted on these vape liquids indicated the route of exposure, storage conditions, and length of storage could expose consumers to unintended cannabinoids and showed a concerning level of disagreement between the products' labeled cannabinoid content and the results generated by these analyses. [ABSTRACT FROM AUTHOR]

Introduction: The goal of this study is to explore the pharmacological potential of the amyloid-reducing vasodilator fasudil, a selective Ras homolog (Rho)- associated kinases (ROCK) inhibitor, in the P301S tau transgenic mouse model (Line PS19) of neurodegenerative tauopathy and Alzheimer's disease (AD). Methods: We used LC-MS/MS, ELISA and bioinformatic approaches to investigate the effect of treatment with fasudil on the brain proteomic profile in PS19 tau transgenic mice. We also explored the efficacy of fasudil in reducing tau phosphorylation, and the potential beneficial and/or toxic effects of its administration in mice. Results: Proteomic profiling of mice brains exposed to fasudil revealed the activation of the mitochondrial tricarboxylic acid (TCA) cycle and blood-brain barrier (BBB) gap junction metabolic pathways. We also observed a significant negative correlation between the brain levels of phosphorylated tau (pTau) at residue 396 and both fasudil and its metabolite hydroxyfasudil. Conclusions: Our results provide evidence on the activation of proteins and pathways related to mitochondria and BBB functions by fasudil treatment and support its further development and therapeutic potential for AD. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a significant source of disability in the United States and around the world and may lead to long-lasting cognitive deficits and a decreased quality of life for patients across injury severities. Following the primary injury phase, TBI is characterized by complex secondary cascades that involve altered homeostasis and metabolism, faulty signaling, neuroinflammation, and lipid dysfunction. The objectives of the present study were to (1) assess potential correlations between lipidome and cytokine changes after closed-head mild TBI (mTBI), and (2) examine the reproducibility of our acute lipidomic profiles following TBI. Cortices from 54 Sprague Dawley male and female rats were analyzed by ultra-high-performance liquid chromatography mass spectrometry (LC-MS) in both positive and negative ionization modes and multiplex cytokine analysis after single (smTBI) or repetitive (rmTBI) closed-head impacts, or sham conditions. Tissue age was a variable, given that two cohorts (n = 26 and n = 28) were initially run a year-and-a-half apart, creating inter-batch variations. We annotated the lipidome datasets using an in-house data dictionary based on exact masses of precursor and fragment ions and removed features with statistically significant differences between sham control batches. Our results indicate that lipids with high-fold change between injury groups moderately correlate with the cytokines eotaxin, IP-10, and TNF-α. Additionally, we show a significant decrease in the pro-inflammatory markers IL-1β and IP-10, TNF-α, and RANTES in the rmTBI samples relative to the sham control. We discuss the major challenges in correlating high dimensional lipidomic data with functional cytokine profiles and the implications for understanding the biological significance of two related but disparate analysis modes in the study of TBI, an inherently heterogeneous neurological disorder. [ABSTRACT FROM AUTHOR]

BACKGROUND: Phthalates are endocrine-disrupting chemicals linked to adverse pregnancy outcomes. Despite the sensitivity of female reproductive processes to oxidation–reduction reaction stress and endocrine disruption, evidence for the impact of women’s phthalate exposure on the ability to establish and maintain pregnancy has been inconclusive. OBJECTIVES: We aimed to determine the relationship of preconception phthalate metabolite exposure with a) fecundability and pregnancy loss and b) markers of potential biological mechanisms, including reproductive hormones, inflammation, and oxidative stress. METHODS: Data were collected from the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial, a preconception study following 1,228 women who were attempting pregnancy, for up to six menstrual cycles and throughout pregnancy if they became pregnant. Twenty phthalate metabolites were measured in a consecutive 3-d pooled urine sample at enrollment. Pregnancy was determined through urinary human chorionic gonadotropin (hCG) at the expected date of menses during each cycle and pregnancy loss as an observed loss following positive hCG. Highly sensitive C-reactive protein (hsCRP) and isoprostanes were measured at enrollment, and reproductive hormones were measured during the follicular phase, ovulation, and luteal phase. Discrete-time Cox proportional hazards models evaluated the relationship of phthalate metabolites with fecundability and weighted Poisson models with robust variance evaluated the risk of pregnancy loss. RESULTS: An interquartile range (IQR) higher mono-(2-ethylhexyl) phthalate [fecundability odds ratio (FOR)=0.88; 95% confidence interval (CI): 0.78, 1.00], mono-butyl phthalate (FOR=0.82; 95% CI: 0.70, 0.96), and mono-benzyl phthalate (FOR=0.85; 95% CI: 0.74, 0.98) was associated with lower fecundability. No consistent associations were observed with pregnancy loss. Preconception phthalates were consistently associated with higher hsCRP and isoprostanes, as well as lower estradiol and higher follicle-stimulating hormone across the menstrual cycle. DISCUSSION: Women’s preconception exposure to phthalates was associated with lower fecundability, changes in reproductive hormones, and increased inflammation and oxidative stress. The pre- and periconception periods may represent sensitive windows for intervening to limit the reproductive toxicity of phthalate exposure. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What metabolic pathways and metabolites in the serum and follicular fluid are associated with peak estradiol levels and the number of mature oocytes? SUMMARY ANSWER In the serum metabolome, mostly fatty acid and amino acid pathways were associated with estradiol levels and mature oocytes while in the follicular fluid metabolome, mostly lipid, vitamin, and hormone pathways were associated with peak estradiol levels and mature oocytes. WHAT IS KNOWN ALREADY Metabolomics has identified several metabolic pathways and metabolites associated with infertility but limited data are available for ovarian stimulation outcomes. STUDY DESIGN, SIZE, DURATION A prospective cohort study of women undergoing IVF from 2009 to 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 125 women undergoing a fresh IVF cycle at a fertility clinic in the Northeast United States who provided a serum and follicular fluid sample. Untargeted metabolomics profiling was conducted using liquid chromatography with high-resolution mass spectrometry in two chromatography columns (C18 and hydrophilic interaction chromatography (HILIC)). The main ovarian stimulation outcomes were peak serum estradiol levels and number of mature oocytes. We utilized adjusted generalized linear regression models to identify significant metabolic features. Models were adjusted for age,BMI, initial infertility diagnosis, and ovarian stimulation protocol. We then conducted pathway analysis using mummichog and metabolite annotation using level-1 evidence. MAIN RESULTS AND ROLE OF CHANCE In the serum metabolome, 480 and 850 features were associated with peak estradiol levels in the C18 and HILIC columns, respectively. Additionally, 437 and 538 features were associated with mature oocytes in the C18 and HILIC columns, respectively. In the follicular fluid metabolome, 752 and 929 features were associated with peak estradiol levels in the C18 and HILIC columns, respectively, Additionally, 993 and 986 features were associated with mature oocytes in the C18 and HILIC columns, respectively. The most common pathways associated with peak estradiol included fatty acids (serum and follicular fluid), hormone (follicular fluid), and lipid pathways (follicular fluid). The most common pathways associated with the number of mature oocytes retrieved included amino acids (serum), fatty acids (serum and follicular fluid), hormone (follicular fluid), and vitamin pathways(follicular fluid). The vitamin D3 pathway had the strongest association with both ovarian stimulation outcomes in the follicularfluid. Four and nine metabolites were identified using level-1 evidence (validated identification) in the serum and follicular fluid metabolomes, respectively. LIMITATIONS, REASONS FOR CAUTION Our sample was majority White and highly educated and may not be generalizable to thewider population. Additionally, residual confounding is possible and the flushing medium used in the follicular fluid could have diluted our results. WIDER IMPLICATIONS OF THE FINDINGS The pathways and metabolites identified by our study provide novel insights into the biologicalmechanisms in the serum and follicular fluid that may underlie follicular and oocyte development, which could potentially be used to improve ovarian stimulation outcomes. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the following grants from the National Institute of Environmental Health Sciences (P30-ES019776, R01-ES009718, R01-ES022955, P30-ES000002, R00-ES026648, and T32-ES012870), and National Institute of Diabetes and Digestive and Kidney Diseases (P30DK046200). The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

With the current crisis related to the diffusion of fentanyl and other novel opioids in several countries and populations, new and effective approaches are needed to better elucidate the phenomenon. In this context, hair testing offers a unique perspective in the investigation of drug consumption, producing useful information in terms of exposure to psychoactive substances. In this research, we applied targeted ultra‐high performance liquid chromatography tandem mass spectrometry (UHPLC–MS/MS) analytical methods to detect novel synthetic and prescription opioids and other common controlled psychoactive drugs in the keratin matrix. A total of 120 hair samples were analyzed from the United States (US) and Italy, segmented when longer than 6 cm, and then analyzed. In the 60 samples (83 segments in total) analyzed from a purposive sample of data collected in the US, fentanyl was detected in 14 cases (16.9%), with no detection of nitazens or brorphine. We also detected fentanyl metabolites, despropionyl‐p‐fluorofentanyl, and prescription opioids. In the 60 samples collected in Italy (91 segments in total), ketamine was the most prevalent compound detected (in 41 cases; 45.1%), with ketamine demonstrating a strong correlation with detection of amphetamines and MDMA, likely due to co‐use of these substances in recreational contexts. Several common drugs were also detected but no exposure to fentanyl or its analogs were detected. Results of this retrospective exploration of drug use add to increasing evidence that hair testing can serve as a useful adjunct to epidemiology studies that seek to determine biologically confirmed use and exposure in high‐risk populations. [ABSTRACT FROM AUTHOR]

The opioid epidemic has affected the United States (US) for decades with fentanyl and its analogs accounting for a recent surge in morbidity and mortality. Currently, there is a relative lack of information characterizing fentanyl‐related fatalities specifically in the Southern US. A retrospective study was conducted to examine all postmortem fentanyl‐related drug toxicities in Travis County, Texas, encompassing Austin (one of the fastest‐growing cities in the US), from 2020 to 2022. Fentanyl contributed to 2.6% and 12.2% of deaths submitted for toxicology between 2020 and 2022, respectively, representing a 375% increase in fentanyl‐related deaths over this 3‐year period (n = 517). Fentanyl‐related fatalities primarily occurred in males in their mid‐30s. Fentanyl and norfentanyl concentrations ranged from 0.58 to 320 ng/mL and 0.53 to 140 ng/mL with mean (median) concentrations of 17.2 ± 25.0 (11.0) and 5.6 ± 10.9 (2.9) ng/mL, respectively. Polydrug use was present in 88% of cases, with methamphetamine (or other amphetamines) (25%), benzodiazepines (21%), and cocaine (17%) representing the most frequently identified concurrent substances. Co‐positivity rates of various drugs and drug classes widely varied over time. Scene investigations reported illicit powder(s) (n = 141) and/or illicit pill(s) (n = 154) in 48% (n = 247) of fentanyl‐related deaths. Illicit oxycodone (44%, n = 67) and illicit "Xanax" (38%, n = 59) pills were frequently reported on scene; however, toxicology only identified oxycodone and alprazolam in 2 and 24 of these cases, respectively. The results of this study provide a better understanding of the fentanyl epidemic in this region creating an opportunity to promote increased awareness, shift focus to harm reduction, and aid in minimizing public health risks. [ABSTRACT FROM AUTHOR]

Objective. Cannabinoid extraction from Cannabis sativa L. (hemp) for nonmedical purposes has become popular in the United States. Concerns, however, have been raised regarding the accuracy of the labels for cannabinoid levels in the commercial products. Methods. In this study, we developed rapid, sensitive, selective, accurate, and validated liquid chromatography-tandem mass spectrometry for the quantification of cannabinoids. The methods are for determining 11 cannabinoids in cannabis (hemp) extracted in oil form, and we investigated the accuracy of the labeling and thermal stability regarding the cannabinoids on 17 oil cannabis samples. Results. In the UPLC chromatogram, we see a good resolution and there is no matrix effect and the accuracy were 98.2% to 102.6%, and the precision was 0.52%–8.18%. The linearity of the calibration curves in methanol was with a regression r2 ≥ 0.99. The lowest of detection (LOD) was 5–25 ng/mL, and the limit of quantification (LOQ) was 10–50 ng/mL. The study showed that only 30% of the commercial samples were within the acceptable range of +/−10% compared to the labeled ingredient concentrations. The thermal stability test profile showed a change in the concentration of cannabinoids in each sample at 37°C for one week, with an average loss of cannabinoids up to 15%. Conclusion. The validated method proved to be selective, accurate, and precise, with acceptable linearity within the calibration range with no matrix effect. The stability profile data indicated that high temperatures could change the quality of commercial samples. [ABSTRACT FROM AUTHOR]

Sex hormones impact body composition. Data on the specific impact of each hormone on different body depots in men and women are scarce. The aim of this study is to evaluate the association between testosterone, estradiol and body fat distribution in the general population. This is a population-based cross-sectional study based on data from the 2013–2016 cycles of the National Health and Nutrition Examination Survey. Dual energy X-ray absorptiometry (DXA) and liquid chromatography tandem mass spectrometry were performed on participants aged 18–59 years to evaluate body composition and sex hormone levels, respectively. Weighted multivariable linear regression analyses were performed to evaluate the association between these parameters after adjustment for potential confounders. A total of 6655 participants (3309 males and 3346 females) was included in the analysis. Men with lower testosterone levels were older, had a higher body mass index (BMI) and had a generally unfavorable metabolic profile, while no specific trends were found in women. Among men, testosterone was positively associated with lean body mass and was negatively associated with fat mass and the android/gynoid (A/G) ratio, while an opposite trend was found for estradiol. Among women, testosterone did not impact body composition, while estradiol levels were positively associated with lean mass and were negatively associated with fat mass. Our results support the notion that the impact of different sex hormones on specific fat depots varies substantially between men and women. [ABSTRACT FROM AUTHOR]

Obesity is one of the leading health concerns in the United States. Studies from human and rodent models suggest that inherent differences in the function of brain motivation centers, including the nucleus accumbens (NAc), contribute to overeating and thus obesity. For example, there are basal enhancements in the excitability of NAc GABAergic medium spiny neurons (MSN) and reductions in basal expression of AMPA‐type glutamate receptors in obesity‐prone vs obesity‐resistant rats. However, very little is known about the regulation of extracellular glutamate and GABA within the NAc of these models. Here we gave obesity‐prone and obesity‐resistant rats stable isotope‐labeled glucose (13C6‐glucose) and used liquid chromatography mass spectrometry (LC–MS) analysis of NAc dialysate to examine the real‐time incorporation of 13C6‐glucose into glutamate, glutamine, and GABA. This novel approach allowed us to identify differences in glucose utilization for neurotransmitter production between these selectively bred lines. We found that voluntarily ingested or gastrically infused 13C6‐glucose rapidly enters the NAc and is incorporated into 13C2‐glutamine, 13C2‐glutamate, and 13C2‐GABA in both groups within minutes. However, the magnitude of increases in NAc 13C2‐glutamine and 13C2‐GABA were lower in obesity‐prone than in obesity‐resistant rats, while basal levels of glutamate were elevated. This suggested that there may be differences in the astrocytic regulation of these analytes. Thus, we next examined NAc glutamine synthetase, GAD67, and GLT‐1 protein expression. Consistent with reduced 13C2‐glutamine and 13C2‐GABA, NAc glutamine synthetase and GLT‐1 protein expression were reduced in obesity‐prone vs obesity‐resistant groups. Taken together, these data show that NAc glucose utilization differs dramatically between obesity‐prone and obesity‐resistant rats, favoring glutamate over GABA production in obesity‐prone rats and that reductions in NAc astrocytic recycling of glutamate contribute to these differences. These data are discussed in light of established differences in NAc function between these models and the role of the NAc in feeding behavior. [ABSTRACT FROM AUTHOR]

Background: Oxytetracycline (OTC), chlortetracycline (CTC), and tetracycline (TC) are approved antibiotics used to treat bacterial infections in cattle. To ensure human food safety, a tolerance has been established for the sum of these three TC residues as 12 parts per million in bovine kidney in the United States The current official regulatory method for quantifying these antibiotics in the target organ is a labor-intensive microbiological assay. Objective: Our laboratory developed and validated a fast, selective, and less laborious method utilizing LC-tandem mass spectrometry for the determination and confirmation of the three tetracyclines (TET) in bovine kidney. Methods: Briefly, homogenized kidney tissue was spiked with an internal standard (ISTD), and then was extracted with 1% phosphate buffer. The crude extract was cleaned up using solid-phase extraction cartridges before instrumental analysis. Results: Accuracies for quantifying these three drugs in fortified kidney homogenate were between 99.9 and 110% at multiple concentrations, with respective CVs all below 9.5%. Quantitative correlation between the two methods (bridging) was evaluated with incurred bovine kidney samples for each of the three tetracyclines separately. The results were statistically evaluated using a measurement model called Functional Relationship Estimation by Maximum Likelihood. Conclusion: A linear quantitative relationship was demonstrated between the two methods within the concentration range of regulatory relevance. Highlights: This instrumental method is in addition to the established microbial assay for the detection of tetracyclines residue in beef kidney to ensure the food safety of cattle products. [ABSTRACT FROM AUTHOR]

Perfluorooctanoic acid (PFOA) is an environmentally persistent perfluoroalkyl substance that is widely used in consumer products. Exposure to PFOA is associated with reproductive and developmental effects including endocrine disruption, delayed puberty in girls, and decreased fetal growth. In the United States, obesity affects 40% of women and 20% of girls, with higher rates in minority females. Obesity causes infertility, poor oocyte quality, miscarriage, and offspring defects. This study proposed that PFOA exposure would impact estrous cyclicity, ovarian steroid hormones, and the ovarian proteome and further hypothesized that obesity would impact PFOA-induced ovotoxicity. Female wild type (KK.Cg-a/a; lean) or KK.Cg-Ay/J mice (obese) received saline (CT) or PFOA (2.5 mg/kg) per os for 15 days beginning at 7 weeks of age. There were no effects on food intake, body weight, estrous cyclicity, serum progesterone, and heart, spleen, kidney, or uterus weight (p  >  .05). Ovary weight was decreased (p  <  .05) by PFOA exposure relative to vehicle control-treated mice in lean but not obese mice. Liquid chromatography-tandem mass spectrometry was performed on isolated ovarian protein and PFOA exposure altered the ovarian abundance of proteins involved in DNA damage sensing and repair pathways and reproduction pathways (p  <  .05) differentially in lean and obese mice. The data suggest that PFOA exposure alters ovary weight and differentially targets ovarian proteins in lean and obese females in ways that might reduce female fecundity. [ABSTRACT FROM AUTHOR]

Frederick K. Humphreys (1816-1900), founder of Humphreys Medicine Company, appeared at the rise of both greater acceptance and popularity of the homeopathy in the United States, as opposed to more orthodox medicine. Although bolstered by the relatively high cost and low success rate of traditional medicines, homeopathic remedies soon became a source of controversy due to the largely unknown ingredient lists and contradictory claims of effectiveness. Tandem mass spectrometry analysis (MS/MS) was used to pinpoint the ingredients of four "specifics" in Humphreys' Homeopathic Remedies. Generated spectra showed similar base peak ions for each pill, leading to the hypothesis that each remedy contained the same basic ingredients. Further MS/MS analyses identified these base peak ions as adducts of sucrose (m/z 365, 381), its related ions (m/z 433, 203, 185), and apigenin (m/z 271). When placed into a historical context, the application of chemical analyses to study these early remedies can provide insight into the question of validity that evoked arguments during the late nineteenth century. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies like Herceptin play a pivotal role in modern therapeutics, with their glycosylation patterns significantly influencing their bioactivity. To characterize the N-glycan profile and their relative abundance in Herceptin, we employed two analytical methods: hydrophilic interaction chromatography with fluorescence detection (HILIC-FLD) for released glycans and liquid chromatography tandem mass spectrometry (LC-MS/MS) for glycopeptides. Our analysis included 21 European Union (EU)-Herceptin lots and 14 United States (US)-Herceptin lots. HILIC-FLD detected 25 glycan species, including positional isomers, revealing comparable chromatographic profiles for both EU and US lots. On the other hand, LC-MS/MS identified 26 glycoforms within the glycopeptide EEQYNSTYR. Both methods showed that a subset of glycans dominated the total abundance. Notably, EU-Herceptin lots with an expiration date of October 2022 exhibited increased levels of afucosylated and high mannose N-glycans. Our statistical comparisons showed that the difference in quantitative results between HILIC-FLD and LC-MS/MS is significant, indicating that the absolute quantitative values depend on the choice of the analytical method. However, despite these differences, both methods demonstrated a strong correlation in relative glycan proportions. This study contributes to the comprehensive analysis of Herceptin's glycosylation, offering insights into the influence of analytical methods on glycan quantification and providing valuable information for the biopharmaceutical industry. • Herceptin is used in the treatment of Her2-overexpressed breast cancer. • HILIC-FLD analysis of released glycans and LC-MS/MS analysis of glycopeptides methods were compared. • HILIC-FLD and LC-MS/MS are orthogonal analytical techniques for quantitative analysis of glycans. • HILIC-FLD is highly sensitive because it involves labeling released glycans with a fluorescent tag. • LC-MS/MS offers specificity because it can localize the glycosylation sites. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the relationship between serum testosterone levels and systemic immune-inflammation index (SII). Methods: Complete SII and serumtestosterone data of men over 20 years of age were retrieved from the 2011--2016 National Health and Nutrition Examination Survey to conduct a prevalence survey. To calculate SII, the platelet count was multiplied by the neutrophil-to-lymphocyte count ratio. Isotope dilution liquid chromatography and tandem mass spectrometry were employed to measure serum testosterone concentration. Testosterone deficiency (TD) was defined as a serum testosterone level ≤ 300ng/dl. Weighted proportions and multivariable regression analyses were used to analyze the association between SII and TD. Results: Overall, the data of 7389 participants were analyzed, The SII ranged from 1.53 - 6297.60. Of the participants, 28.42% had a low serum testosterone level (≤ 300 ng/dl). In the fully adjusted multivariable logistic model, the second quartile (OR: 1.27, p = 0.0737), the third quartile (OR: 1.43, p = 0.0090), and the fourth quartile (OR:1.48, p = 0.0042) of SII significantly increased the TD incidence rate, with the lowest quartile of the SII as a reference. For subgroup analysis, statistically significant associations were observed in participants aged 20-40, obese, non-hypertensive, and non-diabetic. The interaction test revealed no significant effect on this connection. Conclusions: There was a positive relationship between a high SII and an increased prevalence of TD in a nationwide sample of adult men in the United States. Further prospective studies on a larger scale are warranted to confirm the causality between SII and TD. [ABSTRACT FROM AUTHOR]

Background: The relationship between men's testosterone levels and their sexual behaviors is unclear as existing studies find mixed results. Objectives: The key objective of this study is to assess whether men's testosterone levels are affected by sexual behaviors and to explore whether this relationship varies by age. Specifically, this study addresses the question: Are men's testosterone levels affected by the number of sexual partners they accrue? Methods: This analysis was based on a nationally representative sample of 977 unpartnered heterosexual men between the ages of 20 and 65 in the United States. Serum testosterone levels were measured from blood samples using isotope dilution liquid chromatography tandem mass spectrometry and the number of sexual partners in the past 12 months was ascertained from an audio computer‐assisted personal self‐interview. Using ordinary least squares regression, serum testosterone levels were predicted as a function of the number of sexual partners that men reported, sociodemographic characteristics, and factors known to affect endocrine regulation. An interaction term between the number of sexual partners in the past 12 months and age was included. Results: The correlation between the number of sexual partners in the past 12 months and testosterone levels is contingent upon age: The relationship is positive for younger men but negative for older men. Among 20‐year‐old unpartnered heterosexual men, an additional sexual partner in the past 12 months is associated with an increase of 5.55 ng/dl of testosterone (95% confidence interval (CI): 2.92, 8.19). This initial positive effect at age 20 is reduced by 0.25 ng/dl of testosterone (95% CI: −0.44, −0.06) with each year that men age. Conclusion: Testosterone levels in men are related to reproductive behaviors, but the direction of this relationship changes as men age. [ABSTRACT FROM AUTHOR]

Background: Fentanyl, a synthetic opioid, has caused many recent overdose deaths. Diagnosis of fentanyl abuse is not served by traditional opiate assays due to differences in chemical structure between synthetics and natural opioids. To our knowledge, this is the first study that uses liquid chromatography-tandem mass spectrometry (LC-MS/MS) as the reference method to evaluate and compare the ARK Fentanyl II Assay (ARK II) and the Fentanyl II Enzyme Immunoassay by Roche (FEN2). The ARK II is designed to detect fentanyl in urine samples, whereas the FEN2 is designed to detect norfentanyl, which is the major metabolite., Methods: Two hundred patient urine samples including 100 positive and 100 negative samples according to an in-house LC-MS/MS assay were selected for the study. These samples were tested using the ARK II and the FEN2 to determine their performances relative to LC-MS/MS results., Results: The FEN2 showed a positive and negative predictive value of 100% and 97% and a concordance with LC-MS/MS of 98.5% (kappa 0.97). The ARK II showed a positive and negative predictive value of 100% and 95% and a concordance with LC-MS/MS of 97.5% (kappa 0.95). Additionally, the FEN2 accurately identified 9 positive samples with a range of fentanyl concentrations from 0 to 18 ng/mL for which norfentanyl levels were less than the cutoff of 5 ng/mL, indicating potentially greater sensitivity than otherwise stated., Conclusions: The FEN2 and the ARK II were evaluated to be similar in terms of positive and negative predictive value during the analysis of 200 patient samples, as well as equally concordant with the LC-MS/MS reference, despite differences in design., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: Osteoarthritis (OA) is a major concern in the United States and worldwide. Development and validation of robust decellularization techniques is critical in generating suitable bioscaffolds for future OA treatment options. Data descriptions: In the present study, proteins from porcine auricular cartilage before and after decellularization were extracted, digested, and identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The data represents protein profiles of both non-decellularized and decellularized porcine auricular cartilage. This data is intended to be useful to scientists who are interesting in generating biomaterials for potential relevant clinical applications using decellularized cartilage tissue. [ABSTRACT FROM AUTHOR]

• Appendectomy (appy) increases hospital readmission risk directly related to adhesions. • Adhesions may cause small bowel obstruction (SBO) that require adhesiolysis. • Pro- and anti-inflammatory mediators in appy rA may regulate de novo adhesion. • SBO rA showed markers of increased oxidative stress and altered energy metabolism. • Appy rA may represent a suitable fluid to elucidate human adhesion dynamics. Pathological abdominal adhesions can cause bowel obstructions. A history of appendectomy (appy) increases patient rehospitalization risk directly related to adhesions. To potentially identify strategies for adhesion treatment, we characterized reactive ascites (rA) collected during appy or adhesiolysis for small bowel obstruction (SBO). This is a non-randomized, prospective observational study recruiting patients with non-perforated appendicitis or SBO from three Level 1 trauma centers in the United States. rA were analyzed via liquid chromatography-mass spectrometry (LC-MS) (n = 31), bead-based quantification cytokines and chemokines (n = 32) and soluble receptors (n = 30), and LC-MS metabolomics (n = 18). LC-MS showed that samples contained albumin, apolipoprotein A1, and transthyretin and that metabolites increased in SBO vs appy rA were biomarkers of oxidative stress. Multi-plex analyses showed levels of 17 cytokines/chemokines and 6 soluble receptors were significantly different in appy vs SBO rA. Top increased proteins in appy compared to SBO rA by 20.14-, 11.53-, and 8.18-fold were granulocyte-colony stimulating factor, C-X-C motif chemokine ligand 10, and interleukin-10, respectively. These data further define pro- and anti-inflammatory mediators and metabolites that may drive formation or perpetuate chronic abdominal adhesions. Future research is to further explore whether attenuation of these factors may decrease pathologic adhesion formation. [ABSTRACT FROM AUTHOR]

Alpelisib, an oral selective and small-molecule phosphoinositide 3-kinase inhibitor, was lately approved in the United States to treat breast cancer. A sensitive method to quantify alpelisib levels in rat plasma on the basis of ultra-performance liquid chromatography–tandem mass spectrometry technique was established and validated, which was successfully employed to explore the effects of CYP3A4 inhibitors on alpelisib pharmacokinetics in rats. A C18 column named Acquity UPLC BEH C18 was applied to achieve the separation of alpelisib and internal standard duvelisib after protein precipitation with acetonitrile. The mobile phase in this study had two components, namely, acetonitrile and water having 0.1% formic acid, and a program with gradient elution method was used at a flow rate of 0.40 ml/min. Mass spectrometry in a positive multiple reaction monitoring mode was operated. In the scope of 1–5,000 ng/ml, this assay had excellent linearity. Our newly developed assay was verified in all aspects of bioanalytical method validation, involving lower limit of quantification, selectivity, accuracy and precision, calibration curve, extraction recovery, matrix effect, and stability. Then, this assay was used to detect the plasma levels of alpelisib from a drug-drug interaction investigation, where ketoconazole remarkably increased the plasma concentration of alpelisib and changed alpelisib pharmacokinetics more than itraconazole. This study will help better understand the pharmacokinetic properties of alpelisib, and further clinical studies should be done to confirm this result in patients. [ABSTRACT FROM AUTHOR]

Objective: Current evidence on the association between serum testosterone and cognitive performance has been inconsistent, especially in older adults. To investigate the associations between serum testosterone and cognitive performance in a nationally representative sample of older men and women. Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) 2011–2014. 1,303 men and 1,349 women aged 60 years or older were included in the study. Serum total testosterone was preformed via isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) method. Free testosterone was calculated by Vermeulen's formula. Cognitive performance was evaluated by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test, Animal Fluency test, and Digit Symbol Substitution Test (DSST). Binary logistic regression and restricted cubic spline models were applied to evaluate the association of testosterone and cognitive performance. Results: In men, higher concentrations of total testosterone were associated with better performance on CERAD test (OR = 0.51; 95%CI = 0.27–0.95) and DSST (OR = 0.54; 95%CI = 0.30–0.99) in adjusted group. Similarly, higher concentrations of free testosterone were associated with better performance on CERAD test (OR = 0.32; 95%CI = 0.17–0.61) and DSST (OR = 0.41; 95%CI = 0.17–0.96) in men. These associations were not seen in women. Conclusion: Serum testosterone concentrations were inversely associated with cognitive performance in older men but not women in the United States. [ABSTRACT FROM AUTHOR]

Gamma-butyrolactone (GBL), a commonly used industrial solvent, is used recreationally as a central nervous system (CNS) depressant and, therefore, is a United States Drug Enforcement Agency List 1 chemical of the Controlled Substances Act. GBL was identified presumptively in the liquid from JUUL Virginia Tobacco flavored pods during routine untargeted screening analysis of e-cigarette products by gas chromatography–mass spectrometry (GC–MS). Methods for the analysis of GBL were developed for GC–MS and liquid chromatography–tandem mass spectrometry (LC–MS-MS) in the liquids and the aerosol generated from the liquid. Three flavors of JUUL pods available at the time of analysis were obtained by direct purchase from the manufacturer, purchase from a local vape shop and submission from a third party. The only liquid flavor to contain GBL was Virginia Tobacco, with an average of 0.37 mg/mL of GBL, and it was detected in the aerosol. Studies evaluating the pharmacological effects of inhaling GBL do not exist; however, a case report of chronic oral GBL ingestion indicates acute lung injury. The identification of GBL in an e-cigarette product purportedly compliant with federal regulation continues to demonstrate public health and public safety concerns. [ABSTRACT FROM AUTHOR]

The proliferation of misuse of prescription and non‐prescription opioids, in recent years, has caused an opioid epidemic in the United States. Forensic toxicology laboratories often encounter implications of abuse in both driving under the influence of drugs and death investigation cases. The Virginia Department of Forensic Science has seen over a 190% increase in the number of reported opioids in death investigation cases over the past several years. Traditionally, analyses are completed by individual drug class, which subsequently requires an individual case to be evaluated using multiple analytical techniques for comprehensive analysis. To ease the impact of increasing case submissions and case complexity, two liquid chromatography‐tandem mass spectrometry (LCMSMS) methods for the quantitative analysis of opioids, cocaine, and cocaine metabolites in biological matrices have undergone a fit‐for‐purpose validation. The methods were compared to determine the advantages and disadvantages of each analytical technique. Two sample preparation techniques, protein precipitation and solid‐phase extraction, were employed for quantitative validation. Validation aspects evaluated included accuracy and precision, sensitivity, linearity, matrix effects, recovery, carryover, interferences, dilution integrity, and post‐extraction stability. The accuracy of the protein precipitation method ranged from 80 ± 3% to 101 ± 10%. The accuracy of the solid‐phase extraction method ranged from 88 ± 9% to 119 ± 3%. Additionally, within‐run and intermediate precision was within ±20% for both extraction techniques. Although ionization suppression was noted, it was determined to have minimal effect on the methods. The newly developed methods require less sample volume and combine four analytical techniques into one method, which significantly impacts laboratory productivity. [ABSTRACT FROM AUTHOR]

Ectoparasite infestations negatively affect both backyard and commercial chicken flocks in the United States. Fluralaner is an isoxazoline shown to be efficacious in treating mite and bed bug infestations in poultry. Fluralaner is approved to treat fleas and ticks in dogs and cats in the United States and to treat mite infestations of chickens in Europe and Australia; however, the use of fluralaner in poultry is not yet approved in the United States. This study aimed to investigate the plasma fluralaner pharmacokinetic profile of intravenous and transdermal routes and apparent bioavailability of fluralaner administered trans-dermally in healthy shaver hens. A total of 12 individually housed healthy shaver hens received a single dose of either intravenous technical grade fluralaner at 0.5 mg/kg, or transdermal fluralaner (Bravecto (fluralaner transdermal solution) for dogs, 280 mg/mL, Merck Animal Health) at mean 58.7 mg/kg. Plasma from each hen was collected from the jugular, ulnar, or medial metatarsal vein at multiple intervals. Fluralaner concentrations in plasma were determined using Ultra Performance Liquid Chromatography with Mass Spectrometry (UPLC/MS). Noncompartmental analysis revealed that the geometric mean elimination half-life for intravenous and transdermal routes were 80.5 and 179.6 h, respectively. The geometric mean apparent bioavailability of transdermal routes was estimated as 3.4%. Prolonged fluralaner concentration in plasma above minimum inhibitory concentration of bed bugs following the single dose was observed in healthy shaver hens for both routes. It is important to understand the pharmacokinetic profile could be useful in determining the appropriate treatment strategy. [ABSTRACT FROM AUTHOR]

New synthetic opioids continue to appear as novel psychoactive substances (NPS) on illicit drug markets. Isotonitazene emerged in mid‐2019, becoming the most prevalent NPS opioid in the United States within a few months. Notification by the Drug Enforcement Administration of its intent to schedule isotonitazene in mid‐2020 led to its decline in popularity and replacement with a new NPS opioid: brorphine. Brorphine is a potent synthetic opioid, but little information was previously available regarding its toxicity or involvement in impairment and death. Our laboratory developed an assay for the identification and quantitative confirmation of brorphine using standard addition. Quantitative analysis was performed using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). In vitro and in vivo metabolism studies were performed using pooled human liver microsomes and authentic biological specimens, respectively, with analysis by liquid chromatography quadrupole time‐of‐flight mass spectrometry (LC‐QTOF‐MS). Brorphine was confirmed in 20 authentic forensic cases, commonly found in combination with fentanyl (100%) and flualprazolam (80%). The average concentration of brorphine in blood was 2.5 ± 3.1 ng/mL (median: 1.1 ng/mL, range: 0.1–10 ng/mL). The average concentration of brorphine in urine was 4.6 ± 7.6 ng/mL (median: 1.6 ng/mL, range: 0.2–23 ng/mL). The majority of cases originated from Midwestern states. Metabolism was verified to included N‐dealkylation and hydroxylation. Detailed case histories and autopsy findings are presented herein. The prevalence of brorphine continues to increase in the United States. Forensic scientists should remain aware of the ongoing emergence of new opioids, especially those outside a standard scope of toxicology testing. [ABSTRACT FROM AUTHOR]

Understanding in utero transfer of antiretrovirals is critical for interpreting safety. Hair levels measure cumulative exposure. We measured tenofovir (TFV) concentrations in hair at delivery among women living with human immunodeficiency virus receiving TFV disoproxil fumarate-based treatment and their infants, using liquid chromatography-tandem mass spectrometry. Among 103 mother-infant pairs, the mean log10 ratio of infant-to-maternal TFV levels was 1.08 (95% confidence interval, .97-1.20). TFV transfer was 60% lower from mothers who had preterm compared with term deliveries and 42% lower from mothers who had cesarean compared with vaginal deliveries. Like prior studies assessing transfer via short-term measures (plasma, cord blood, amniotic fluid), we found high cumulative transfer using hair. [ABSTRACT FROM AUTHOR]

Deflazacort (Emflaza) was approved in the United States in 2017 for the treatment of the Duchenne muscular dystrophy in patients aged 2 years and older. Several deflazacort metabolites were isolated and identified from rats, dogs, monkeys, and humans. Among them, 1β,2β-epoxy-3β-hydroxy-21-desacetyl deflazacort, referred to as Metabolite V, was reported to be one of the major circulating metabolites in humans. However, its quantitative distribution in plasma was not fully characterized. The objective of this study was to determine deflazacort plasma pharmacokinetics, metabolite profiles and their quantitative exposures in humans following a single oral dose. Six healthy male subjects were each administered a single oral dose of 60 mg [14C]-deflazacort. Plasma and urine were collected and deflazacort metabolites in plasma were quantified by high performance liquid chromatography radio-profiling followed by liquid chromatography-mass spectrometry characterization. Metabolite V was isolated from urine and its structure was further confirmed by nuclear magnetic resonance analysis. These analyses demonstrated that deflazacort was not detectable in plasma; of the eight circulating deflazacort metabolites identified or characterized, the pharmacologically active metabolite 21-desacetyl deflazacort and inactive metabolite 6β-hydroxy-21-desacetyl deflazacort accounted for 25.0% and 32.9% of the 0-24 hours plasma total radioactivity, respectively, while Metabolite V, an epoxide species, was a minor circulating metabolite, representing only about 4.7% of the total plasma radioactivity. [ABSTRACT FROM AUTHOR]

Introduction: Approximately the same percentage of male high school students in the United States currently uses conventional smokeless tobacco as smokes cigarettes, resulting in toxin exposure.Methods: This study assessed tobacco product use (smokeless, combustible, and electronic cigarettes) and nicotine and carcinogen exposures in a sample of 594 male rural high school baseball players-a population traditionally at risk for smokeless tobacco use. Salivary specimens were assayed for cotinine (a biomarker of nicotine exposure) and urine specimens for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, a biomarker of the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) using liquid chromatography-tandem mass spectrometry.Results: The prevalence of past 30-day use of any tobacco product was 29%. Past 7-day smokeless tobacco use (prevalence: 13%) was associated with the highest levels of cotinine and NNAL observed in the sample, whether smokeless tobacco was used exclusively (geometric means: cotinine 11.1 ng/mL; NNAL 31.9 pg/mg-creatinine) or in combination with combustible products (geometric means: cotinine 31.6 ng/mL; NNAL 50.0 pg/mg creatinine). Cotinine and NNAL levels were incrementally higher in each increasing category of smokeless tobacco use frequency. However, observed levels were lower than previously reported for adults, likely reflecting less smokeless use per day among adolescents.Conclusions: Based on these biomarker observations, adolescents who use conventional smokeless tobacco products are exposed to substantial levels of nicotine and NNK. Although exposed to lower levels than adult smokeless users, the findings are concerning given the young age of the sample and tendency for smokeless tobacco users to increase use intensity over time.Implications: This study demonstrates that adolescents using smokeless tobacco are exposed to levels of nicotine and NNK that increase with use frequency and that exceed exposures among peers using other tobacco products. Youth smokeless tobacco use in the United States has not declined along with youth smoking prevalence, giving greater importance to this health concern. To reduce youth (and adult) exposures, needed actions include effective smokeless tobacco use prevention, potentially in combination with reducing the levels of harmful and potentially harmful chemicals in smokeless tobacco products currently popular among adolescents. [ABSTRACT FROM AUTHOR]

In this study, a novel LC-MS/MS (Liquid Chromatography-Tandem Mass Spectrometry) method was designed using a simple extraction procedure that was scientifically developed to capture the most relevant stimulants, methamphetamine, MDA (3,4-Methylenedioxyamphetamine), MDMA (3,4-Methylenedioxy-methamphetamine), and MDEA (Methyl diethanolamine). The LC-MS/MS method was validated using US FDA (United States Food and Drug Administration) guidelines, and all validation requirements were satisfactory. This protein precipitation method was specifically developed for handling large numbers of samples with minimum cost and volume of sample. The developed method was accurate, precise, and reproducible for quantification of stimulant from human plasma. This pilot study enrolled 100 drug addicts to evaluate stimulant testing from plasma. Our findings found 47 cases with positive methamphetamine. This method may be valuable for stimulant blood screening for a large and varied population because of its efficiency and economical aspects. [ABSTRACT FROM AUTHOR]

Background: Cannabis legalization is expanding rapidly throughout the United States, but there is no reliable means of establishing recent use. Objective: To develop and validate a bioanalytical method for determination of Δ9-tetrahydrocannabinol (Δ9-THC), cannabinol, 11-hydroxy-Δ9-THC, 11-nor-9-carboxy-Δ9-THC, and 8b,11-dihydroxy-Δ9-THC in whole blood microsamples by liquid chromatography high-resolution mass spectrometry (LC-HRMS). Methods: Cannabinoid extraction from whole blood was performed using a mixture of n-hexane/ethyl acetate (90:10, v/v). Chromatographic separation was performed with a C18 column using a binary mobile phase gradient of water and acetonitrile, each with 0.1% formic acid. Detection was performed by positive ion mode heated electrospray ionization with full scan MS on an Orbitrap mass spectrometer. A clinical study was performed in 30 subjects to identify recent cannabis use based on analysis of cannabinoids in blood samples up to 200 min post-smoking. Results: Acceptable linearity of all calibration curves was observed (r²>0.99) for all analytes over a 1–100 ng/mL concentration range, with acceptable accuracy. Limit of detection (LOD) was 0.5 ng/mL. Accuracy and precision met acceptance criteria for all analytes. Repeatability (CV) was <5% at low (3 ng/mL) and high (90 ng/mL) concentrations. In the clinical study, the ratios between 11-nor-9-carboxy-Δ9-THC and Δ9-THC fell immediately after smoking and returned to near baseline levels by 200 min post-smoking, which is consistent with recent use. Conclusions and Highlights: The developed LC-HRMS bioanalytical method is suitable for quantification of five key cannabinoids in whole capillary blood microsamples and can be used in conjunction with a test for determining recent cannabis use. [ABSTRACT FROM AUTHOR]

Synthetic cannabinoids pose significant threats to public health and safety, as their implications in overdose and adverse events continue to arise in United States and around the world. Synthetic cannabinoids have seen several generations of chemically diverse structural elements, impacting potency and effects. These factors create new analytical challenges for forensic laboratories. This report describes an efficient liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) assay for the identification of synthetic cannabinoid parent compounds and metabolites, including real-time identification of emergent compounds, using a SCIEX TripleTOF® 5600+ with non-targeted SWATH® acquisition. Method validation evaluated precision/accuracy, limits of detection, interferences, processed sample stability and carryover, for which 19 parent compounds and 19 metabolites were tested. To demonstrate feasibility, de-identified blood sample extracts were acquired from a large forensic toxicology laboratory and analyzed using the validated LC-QTOF-MS assay. In mid-2018, 200 blood extracts were analyzed, demonstrating a 19% positivity rate with > 94% agreement rate with original testing. In addition, three newly discovered synthetic cannabinoids were identified, including 5F-MDMB-PICA, 4-cyano CUMYL-BUTINACA and 5F-EDMB-PINACA. These synthetic cannabinoids were previously unreported in forensic toxicology casework in the United States. 5F-MDMB-PICA has become the most prevalent synthetic cannabinoid in United States, as of early 2019. These results demonstrate the effectiveness of this assay and workflow in the identification and characterization of synthetic cannabinoids, as well as the usefulness of sample-mining using non-targeted mass acquisition by LC-QTOF-MS for the discovery of NPS. High resolution mass spectrometry should be considered when developing new or novel assays for synthetic cannabinoids. [ABSTRACT FROM AUTHOR]

The commercialization in 2016 of genetically engineered seeds tolerant to dicamba and/or 2,4-dichlorophenoxyacetic acid (2,4-D) has caused a rapid increase in the use of these herbicides. New questions about the reproductive and chronic health effects of long-term exposure to these herbicides have been raised. To assess exposure to dicamba and other pesticides of interest in the Heartland Study, a birth cohort study based in the United States, a new analytical method was needed. The present study describes the development and validation of this new solid phase extraction and liquid chromatography-tandem mass spectrometry method that detects simultaneously 13 pesticides or their metabolites in 250 μL of urine. More specifically, the method allows the analysis of dicamba, 2,4-D and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), which are herbicides, of malathion dicarboxylic acid (MDA), para -nitrophenol (PNP), 3,5,6-trichloro-2-pyridinol (TCPy), 2-diethylamino-6-methylpyrimidin-4-ol (DEAMPY) and 2-isopropyl-6-methyl-4-pyrimidinol (IMPY), which are metabolites of organophosphate insecticides, and finally of cis -3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis -DCCA), trans -3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (trans -DCCA), 3-Phenoxybenzoic acid (3-PBA), 4-Fluoro-3-phenoxybenzoic acid (4-F-3-PBA) and cis -3-(2,2-Dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis -DBCA), which are metabolites of synthetic pyrethroids insecticides. The method was validated under ISO/IEC 17025 guidance. The limit of detection (LOD) in urine samples was 0.10 μg/L for dicamba, while the LOD for other analytes ranged between 0.0038 μg/L and 0.091 μg/L. Accuracy was evaluated by analyzing samples from two External Quality Assessment Schemes, namely G-EQUAS and OSEQAS. Preliminary results obtained following the analysis of 91 urine samples taken from pregnant women enrolled in the Heartland Study are presented here. This method is suitable for human biomonitoring studies. [Display omitted] • LC-MS/MS method measuring 13 analytes in urine, useful for biomonitoring. • Analytes included were herbicides like dicamba and 2,4-dichlorophenoxyacetic acid. • Metabolites of organophosphate and synthetic pyrethroid insecticides were included. • Method limits of detection ranged between 0.0038 and 0.10 μg/L. • Dicamba was detected in 70% of samples from pregnant women in the Heartland Study. [ABSTRACT FROM AUTHOR]

The aim of this survey was to compare the occurrence and contamination levels of six major mycotoxin categories found in corn and corn by-product feed ingredients harvested in the United States from 2018 through 2022. Mycotoxins are secondary fungal metabolites that can negatively impact animal health and performance and have been routinely found in a variety of feedstuffs including, but not limited to, cereal grains, by-products, silages, dry hays and pasture grasses. Mycotoxin categories evaluated in this survey included: aflatoxins (AFLA), type A trichothecenes (A-Trich), type B trichothecenes (B-Trich), fumonisins (FUM), zearalenone (ZEN), and ochratoxin A (OTA). This study includes data from corn samples labeled as 2022 harvest and corn b-product feed ingredients submitted from October 2022 through March 2023 and were analyzed for 17 different metabolites via the Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) method. Samples that tested above the limit of detection for each mycotoxin group were analyzed using the generalized linear mixed model procedure of SAS (SAS 9.4, Cary, NC) using harvest year as a fixed effect. The effect of harvest year on average contamination level for each mycotoxin is presented in Table 1. For 2022 harvest year, 260 corn samples and 66 corn by-product samples have been evaluated to date. Mean B-Trich, ZEN, FUM and AFLA levels (parts per billion, ppb) for corn grain samples were similar in 2022 as previous years (P > 0.05). However, for corn grain samples, FUM prevalence and concentration were numerically greater in 2022 than in 2021 and 2020. In the 66 samples of corn by-products, FUM was found in all the samples (100%) and B-Trich were found in the majority of the samples (97%). Mean concentration of FUM in 2022 corn by-product samples was greater (P < 0.001) compared with 2021. Preliminary results of this survey suggest mycotoxin occurrence and contamination remains similar to previous harvest years except for greater mean FUM concentration levels in corn and corn by-products feed ingredients. [ABSTRACT FROM AUTHOR]

Mycotoxins are harmful secondary fungal metabolites detrimental to animal health, even at reduced quantities. Focus on clinical signs such as decreased feed intake and vomiting overlook impacts of mycotoxicosis, including increased disease incidence and severity, immune modulation, inflammation, and gastrointestinal disorders. This study was conducted to compare mycotoxin contamination of initial samples of the 2022 corn crop with previous year trends. Samples were analyzed utilizing the liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for six major mycotoxin groups: aflatoxins (Afla), type A trichothecenes (A-Trich), type B trichothecenes (B-Trich), fumonisins (FUM), zearalenone (ZEN), and ochratoxin A (OTA). The 2022 crop year data were compared with the prior four harvest years using GLIMMIX procedure of SAS with harvest year as fixed effect and sample as the experimental unit. A limited number of samples is available thus far (n = 44) as harvest is still progressing, therefore the risk profile of this crop year is likely to change as the sample pool expands. Contamination levels in corn for the tested toxin groups have remained consistent over the survey period. To date, 97% of the samples evaluated contained at least one mycotoxin, compared with 90% that was observed in 2021. The percentage of Afla contaminated samples increased (P < 0.05) in 2022 corn compared with the 2020 and 2021 harvest years (42 vs. 5 and 7%). The percentage of FUM contaminated samples in 2022 corn is greater (P < 0.05) compared with 2020 and 2021 (88 vs. 64 and 64%). The preliminary results of the 2022 US corn crop survey indicate mycotoxin occurrence and contamination levels are similar or greater (Afla and FUM) to the prior crop year and will continue to challenge animal health and performance as these ingredients are fed out. [ABSTRACT FROM AUTHOR]

The hypolipidemic and hypoglycemic drug benfluorex was widely applied to treat type 2 diabetes mellitus and metabolic syndrome in overweight patients since 1976. However, benfluorex was connected to multiple cases of valvular heart disease and pulmonary arterial hypertension later on. Similar adverse drug reactions were previously found to be associated to the structurally related drug fenfluramine, which was attributed to the formation of its N -deethylated metabolite norfenfluramine. Even though norfenfluramine was known to be a common metabolite of fenfluramine and benfluorex, only fenfluramine was withdrawn from European and United States markets in 1997 while benfluorex remained available until 2009. In this work, the metabolism of benfluorex is simulated by an online hyphenation of electrochemistry and mass spectrometry and the observed transformation products are further characterized using liquid chromatography and high-resolution tandem mass spectrometry. Using this approach, norfenfluramine is found to be the main electrochemical transformation product of benfluorex. Considering the knowledge about norfenfluramine toxicity, rapid metabolite screening using electrochemistry hyphenated to mass spectrometry could have been used to predict the potential of benfluorex for adverse drug reactions early on, showcasing the value of electrochemical metabolism mimicry for rapid drug safety evaluation. • Electrochemistry-mass spectrometry was used to simulate benfluorex metabolism. • Five electrochemical transformation products of benfluorex were identified. • The toxic metabolite norfenfluramine is the most abundant electrochemical product. • Electrochemical metabolite prediction supports toxicological evaluation of drugs. [ABSTRACT FROM AUTHOR]

BACKGROUND Croton oil (CO) is used by dermatologists and plastic surgeons in deep chemical peels. It is mixed with phenol, water, and a soap in Baker-Gordon's or Hetter's formulas. There is controversy as to whether CO or phenol is the active agent in the dermal effect of deep chemical peels. OBJECTIVE To better clarify the role of CO in deep peels, by identification of active compounds in commercially available CO in the United States and biological effects in vivo. MATERIALS AND METHODS Liquid chromatography-tandem mass spectrometry on CO and a domestic pig model experiment using 3 different formulas: G1: 5% Septisol (SEP), G2: 1.6% croton oil in 35% phenol with 5% SEP, and G3: 35% phenol with 5% SEP. RESULTS Liquid chromatography-tandem mass spectrometry indicated the presence of phorbol esters. G1 was null overall. Extent of the coagulative necrosis: G2.G3. Vascular ectasia: G2.G3. Inflammation pattern: intense neutrophilic inflammatory band in G2 versus mild, sparse, perivascular mononuclear cell infiltrate in G3. Neocollagenesis: pronounced in G2, negligible in G3. CONCLUSION Coagulative necrosis of the epidermis, superficial fibroblasts, and vasculature can be attributed to the action of phenol. Phorbol esters on CO could be responsible for the dense deep acute inflammation and the distinctive neocollagenesis. [ABSTRACT FROM AUTHOR]

Access to near-real time opioid use data is essential to the effective management of the U.S. opioid crisis. Current narcotic data collection methods are limited by time delay and would be complimented by a rapid data acquisition technique. Use of wastewater-based epidemiology (WBE) analysis may offer access to near real-time data on opioid consumption but application in the United States has been limited. From 2015 to 2017, monthly 24-h time-weighted composite samples of municipal raw wastewater from two Midwestern U.S. cities were routinely analyzed using liquid chromatography-tandem mass spectrometry for morphine, codeine, oxycodone, heroin, fentanyl, and select opioid metabolites. Concentrations of opioids (ng/L) in raw wastewater from City 1 and 2, respectively, were: morphine (713 ± 38; 306 ± 29; detection frequency (DF): 100%), oxycodone (17.8 ± 1.1; 78 ± 6; DF: 100%), codeine (332 ± 37; 100 ± 27; DF: 93%), heroin (41 ± 16; 9 ± 11; DF: 81%), and fentanyl (1.7 ± 0.2; 1.0 ± 0.5; DF: 62%). Average opioid consumption rates estimated using WBE ranged between 9 and 2590 mg/day/1000 persons. Anticipated overdoses and overdose-deaths calculated from analyte concentrations in wastewater forecasted 200 opioid-related overdoses/year and 39 opioid related overdose-deaths/year across the two cities during the year 2016, which aligned well with observed coroner-reported opioid deaths. This long-term U.S. screening study of opioids in wastewater was the first to utilize wastewater epidemiological data to estimate the number of expected overdose and overdose-deaths, and to identify detectable levels of the powerful synthetic opioid fentanyl in community wastewater consistently over the course of one whole year. Image 1 • Highlights (85 characters per bullet): • Two-year WBE study of opioid use in the American Midwest. • Analysis of cities with known and identified opioid abuse problems. • First estimation of overdoses and deaths from WBE data. • First routine detection of fentanyl and norfentanyl in U.S. wastewater. [ABSTRACT FROM AUTHOR]

• A simple bioanalytical method was first established and validated for CBMIDA. • Direct determination of the chelator itself instead of metal complex. • Improved peek shape was achieved by pulse gradient method. • Poor accuracy and linearity were overcome by addition of EDTA in the mobile phase. • Successful application to pharmacokinetic study. It is usually somewhat difficult to analyze the metal chelators, especially in complex biological matrix, because of the interference of metal ions in both the matrix and analyzing system. In this study, an innovative and simple bioanalytical method was established and validated for the quantification of a newly developed uranium chelator catechol-3, 6-bis (methyleiminodiacetic acid) (CBMIDA) in beagle dog plasma. Different analytical columns and mobile phase were tested for effective chromatography resolution and sensitive and reproducible response of CBMIDA and the internal standard. An Agilent Zorbax SB AQ column was chosen. Excessive peak tailing, peak asymmetry, low recovery, and poor reproducibility, which are generally observed in chromatographic analysis of metal chelators, were overcome by the use of a pulse gradient method and addition of ethylene diamine tetraacetic acid (EDTA) to the mobile phase at 8 μg mL−1, enabling good peak shape, low matrix interference, high precision and good linearity for CBMIDA quantification in beagle dog plasma. Plasma sample pretreatment was performed by a simple, high throughput protein precipitation step with 2.5 mM EDTA methanol solution in a 96-well protein precipitation plate without complexing with the metal ions, and the sample was directly analyzed by electrospray ionization mass spectrometry. By shifting the analysis target from the metal complex to metal chelator itself, the method has an advantage over the existing method for determination of EDTA and diethylenetriaminepentaacetic acid owing to increased sample throughput and apparent simplicity. The assay was validated in accordance with the United States Food and Drug Administration guidelines and successfully applied to the pharmacokinetic study of CBMIDA in beagles after intramuscular injection of CBMIDA at different doses. The method was sensitive enough for the detection of CBMIDA concentration at 4 elimination half-times. The experimental strategies presented herein may be helpful for the measurement of other radionuclide chelators in biological matrices. [ABSTRACT FROM AUTHOR]

Abstract Freshwater bivalve populations are stressed by watershed development at the global scale. Though pharmaceuticals released from wastewater treatment plant effluent discharges are increasingly reported to bioaccumulate in fish, an understanding of bioaccumulation in bivalves is less defined. In the present study, we examined accumulation of 12 target pharmaceuticals in C. fluminea during a 42 day in situ study in Pecan Creek, an effluent dependent wadeable stream in north central Texas, USA. Caged clams were placed at increasing distances (5 m, 643 m, 1762 m) downstream from a municipal effluent discharge and then subsampled on study days 7, 14, 28 and 42. Acetaminophen, caffeine, carbamazepine, diltiazem, diphenhydramine, fluoxetine, norfluoxetine, sertraline, desmethylsertraline, and methylphenidate were identified in C. fluminea whole body tissue homogenates via isotope dilution liquid chromatography-tandem mass spectrometry. Tissue concentrations ranged from low μg/kg (methylphenidate) to 341 μg/kg (sertraline). By study day 7, rapid and apparent pseudo-steady state accumulation of study compounds was observed in clams; this observation continued throughout the 42 d study. Notably, elevated bioaccumulation factors (L/kg) for sertraline were observed between 3361 and 6845, which highlights the importance of developing predictive bioaccumulation models for ionizable contaminants with bivalves. Future research is also necessary to understand different routes of exposure and elimination kinetics for pharmaceutical accumulation in bivalves. Highlights • Pharmaceutical bioaccumulation by bivalves is poorly understood in urban ecosystems. • Rapid uptake observed in clams caged incrementally downstream from effluent discharge. • Spatiotemporal uptake by clams and bioaccumulation factors differed among chemicals. • Exposure route influences on uptake and elimination kinetics require further study. [ABSTRACT FROM AUTHOR]

Odontocete cetaceans bioaccumulate high concentrations of endocrine disrupting persistent organic pollutants (POPs), including dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyltrichloroethylene (DDE), and dichlorodiphenyldichloroethane (DDD) – collectively DDTs – but few studies have explored DDTs-mediated endocrine disruption in cetaceans. Herein, we use remotely collected blubber biopsies from common bottlenose dolphins (Tursiops truncatus) inhabiting a site with high localized DDTs contamination to study the relationships between DDTs exposure and steroid hormone homeostasis in cetaceans. We quantified blubber steroid hormone concentrations by liquid chromatography-tandem mass spectrometry and blubber POP concentrations by gas chromatography-mass spectrometry. We detected six steroid hormones in blubber, including progesterone (P 4), 17-hydroxyprogesterone (17OHP 4), androstenedione (AE), testosterone (T), cortisol (F), and cortisone (E). Sampled dolphins (n = 62) exhibited exposure to DDT, DDE, DDD, chlordanes (CHLDs), mirex, dieldrin, hexachlorobenzene, polychlorinated biphenyls (PCBs), and brominated diphenyl ethers (BDEs). Using principal components analysis (PCA), we determined that blubber DDTs primarily loaded to the first principal component (PC1) explaining 81.6% of the total variance in POP exposure, while the remaining POPs primarily loaded to the PC2 (10.4% of variance). PC1 scores were negatively correlated with blubber T in males and blubber F in females, suggesting that exposure to DDTs impacted androgen and corticosteroid homeostasis. These conclusions were further supported by observed negative correlations between T and o,p'- DDE, o,p'- DDD, and p,p' -DDD in males sampled in the fall, and between F and the six individual DDTs and ∑ 6 DDTs in females. Overall, these results suggest that POP-mediated endocrine disruption may have occurred in this stock of dolphins, which could negatively impact their health and fitness. However, this study relied on uncontrolled incidental exposures, making it impossible to establish a causal relationship between DDTs exposure and endocrine effects. Importantly, this study demonstrates that remotely collected blubber biopsies are a useful matrix for studying endocrine disruption in marine mammals. Image 1 • First study of DDTs-mediated endocrine disruption in common bottlenose dolphins • Organochlorine pesticide exposure linked to disrupted testosterone and cortisol homeostasis • Remote blubber biopsies are useful for studying marine mammal endocrine disruption Bottlenose dolphins in Florida, USA continue to be exposed to the banned pesticide DDT and may be exhibiting impaired endocrine (hormone) health as a result. [ABSTRACT FROM AUTHOR]

Highlights • N -glycans containing O -acetylated SA affect therapeutic glycoprotein efficacy. • O -acetylated glycans of Myozyme for treating Pompe disease have not been reported. • This study investigated O -acetylated glycans on Myozyme using LC-ESI-HCD-MS/MS. • Four types of 17 O -acetylated glycans constitute 6.4% of Myozyme's total glycans. • Glycopeptide analysis by nano-LC-ESI-HCD-MS/MS confirmed six O -acetylation sites. Abstract O -acetylated sialic acid (SA) attached to the N -glycans of therapeutic glycoproteins reportedly inhibit sialidase activity, increase protein half-life, decrease protein antigenicity, and stabilize protein conformation. Recombinant human acid α-glucosidase (Myozyme) is the only drug approved by the United States Food and Drug Administration for the treatment of Pompe disease. In this study, unreported N -glycans containing O -acetylated SA in Myozyme and the relative quantities of total glycans were investigated using liquid chromatography (LC)-electrospray ionization (ESI)-high-energy collisional dissociation (HCD) tandem mass spectrometry (MS/MS). The 17 N -glycans (6.4% of total glycans) containing mono-, di-, mono/di-, and di/di- O -acetylated N -acetylneuraminic acid (Neu5Ac) were identified with mass accuracy, glycan-generated fragment ions, and the retention time on an LC column. The analysis of peptides containing mono- and/or di- O -acetylated Neu5Ac ions sorted from all peptides using nano-LC-ESI-HCD-MS/MS confirmed six O -acetylation sites (Asn 140, Asn 233, Asn 390, Asn 470, Asn 652, and Asn 882), at least five of which (Asn 140, Asn 233, Asn 390, Asn 470, and Asn 652) could contribute to the drug efficacy or cellular uptake of Myozyme. This is the first study to identify N -glycans containing O -acetylated Neu5Ac and O -acetylation sites in Myozyme. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Seven antimicrobials were extracted from 80 U.S. dust samples. • Parabens, triclosan and triclocarban were ubiquitous in U.S. indoor dust. • Triclosan levels in dust were higher in athletic facilities than in homes. • Study establishes antimicrobial levels in U.S. indoor dust prior to TCS and TCC ban. • Median estimated daily intake (EDI) was the highest for toddlers and infants. Abstract Antimicrobials in indoor dust pose concerns due to their endocrine disrupting activities and potential promotion of antibiotic resistance. We adopted dispersive solid phase extraction (d-SPE) and liquid chromatography-tandem mass spectrometry (LC–MS/MS) to quantify antimicrobials in dust. The method showed favorable linearity (R2 >0.99), recovery (83–115%), and method detection limits (1.2–5.6 ng/g, dry weight). All seven analytes were found at median concentrations in ng/g in each of the 80 U.S. dust samples collected from athletic facilities and residential homes: methyl paraben (1920) > propyl paraben (965) > triclosan (390) > triclocarban (270) > ethyl paraben (195) > butyl paraben (80) > benzyl paraben (6). Triclosan levels in dust from athletic facilities were significantly higher than those in private homes (p < 0.05). Median estimated daily intake (EDI) of antimicrobials in ng/kg-body weight/d from dust ingestion was lowest for adults (1.9) and higher for more sensitive subpopulations, including infants (19.8), toddlers (23.6), children (11.8) and teenagers (4.6). This first application of d-SPE to the analysis of dust produced U.S. baseline data for triclosan and triclocarban levels in indoor dust just prior to the 2017 Federal ban on use of these trichlorinated aromatics in antiseptic soaps and related personal care products. [ABSTRACT FROM AUTHOR]

Background: Self-rated health is a commonly used global indicator of health status. Few studies have examined the association of self-rated health and mobility with estrone and estradiol in men. Accordingly, we determined the cross-sectional, incident, and mediating relations between circulating estrone and estradiol levels with self-rated health, mobility limitation, and physical performance in community-dwelling men.Methods: The cross-sectional sample included 1,148 men, who attended Framingham Offspring Study Examinations 7 and 8. Estrone and estradiol levels were measured using liquid chromatography tandem mass spectrometry at Examination 7. Self-reported mobility limitation and self-rated health were assessed at Examinations 7 and 8. Additionally, short physical performance battery, usual walking speed, and grip strength were assessed at Examination 7.Results: In incident analysis, estradiol levels at Examination 7 were associated with increased odds of fair or poor self-rated health at Examination 8, after adjusting for age, body mass index, comorbidities, and testosterone levels; in an individual with 50% greater estradiol than other, the odds of reporting "fair or poor" self-rated health increased by 1.78 (95% confidence interval: 1.25-2.55; p = .001). Neither estrone nor estradiol levels were associated with any physical performance measure at baseline.Conclusions: Higher circulating levels of estradiol are associated with increased risk of incident fair/poor self-rated health in community-dwelling men. The mechanisms by which circulating levels of estradiol are related to self-rated health in men need further investigation. [ABSTRACT FROM AUTHOR]

Carfentanil is a mu (μ) opioid receptor agonist and is estimated to be ~10,000 times more potent than morphine in animal (non-human) models. It is not approved for human use and is only used to immobilize large exotic animals in veterinary medicine. In mid-2016, carfentanil emerged as a contaminant in street heroin in the USA and was central to a large number of emergency department visits and deaths. We describe an analytical method for the detection and quantification of carfentanil in whole blood specimens via a protein precipitation extraction with acetonitrile and liquid chromatography with triple quadrupole mass spectrometry. From 1 September 2016 to 1 January 2017, carfentanil was identified in 262 postmortem blood specimens. Blood concentrations ranged from 10.2 to 2,000 ng/L, with a mean concentration equal to 193 ng/L and a median concentration equal to 98.4 ng/L. We describe 13 fatalities from the Midwest region (Indiana, Kentucky, Michigan and Ohio) of the USA in which our laboratory performed comprehensive toxicology and in which carfentanil was detected and associated with cause of death. We recommend that any analytical method applied to the detection of this substance in human whole blood specimens be sufficiently sensitive to detect sub-100 ng/L concentrations and preferably utilize a 10-50 ng/L reporting limit. [ABSTRACT FROM AUTHOR]

Sorghum is a genus of plant in the grass family, which is used for both grain and forage production throughout the world. In the United States, sorghum grain is predominantly used as livestock feed, and in ethanol production. In recent years however, sorghum grain has been investigated for other industrial applications, including gluten free food sources for the US food market, and waxes. The United States is the world's largest producer of grain sorghum, which is grown in the arid regions of the southern Great Plains, Arizona and California. Carnauba wax is used in a variety of products; including cosmetics, industrial polishes, food products, and paper products. The United States has no domestic source of carnauba wax, and imports 100% of its carnauba wax supply. Sorghum wax has demonstrated similar physical properties to carnauba wax, and could potentially be a viable substitute for carnauba wax. In this paper we present the first successful reversed phase HPLC method, via a C30 column, for the analysis and characterization of waxes, without the need for specialized columns or sample derivation. Sorghum wax is composed of a heterogeneous mixture of compounds, dominated by C28 and C30 saturated and unsaturated species, while carnauba is more homogeneous in nature, and composed primarily of C56-C60 saturated wax esters. [ABSTRACT FROM AUTHOR]

In the present study, 40 freshwater sediments collected near 14 wastewater treatment plants (WWTPs) across the United States were analyzed for eight N -nitrosamines by liquid chromatography-tandem mass spectrometry (LC–MS/MS). Three N -nitrosamines were detected for the first time in freshwater sediments in units of ng/g dry weight at the specified detection frequency: N -nitrosodibutylamine (NDBA; 0.2–3.3; 58%), N -nitrosodiphenylamine (NDPhA; 0.2–4.7; 50%), and N -nitrosopyrrolidine (NPYR; 3.4–19.6; 18%). At least one N -nitrosamine was detected in 70% (28/40) of sediments analyzed. Non-detect values in units of ng/g dw were obtained for N- nitrosodimethylamine (NDMA; <10.2), N -nitrosomethylethylamine (NMEA; <1.7), N -nitrosodiethylamine (NDEA; <3.9), N -nitroso-di- n -propylamine (NDPA; <1.7), and N -nitrosopiperidine (NPIP; <3.6). Principal component analysis specifically points to two of multiple potential pathways explaining N -nitrosamine occurrences in sediment: NDBA and NDPhA were positively correlated with bulk water ammonia and pH levels, and NPYR with sediment content of organic carbon and iron. Interestingly, N -nitrosamine occurrences up- and downstream of WWTPs were statistically indistinguishable ( p > 0.05). This is the first report on the occurrence of the carcinogenic N -nitrosamines NDBA, NDPhA, and NPYR in U.S. freshwater sediments. Discovery of this phenomenon warrants further research on the compounds’ origin, environmental persistence, aquatic toxicity, and risks posed. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA) is a possible human carcinogen and occurs frequently in cereal grain, soy, and other agricultural commodities. Infants and young children may be more susceptible to contaminants than adults because of their lower body weight, higher metabolic rate, reduced ability to detoxify food toxicants, and more restricted diet. The purpose of this study was to investigate the occurrence and levels of OTA in infant formula and infant cereal products available in the U.S. market. In the present study, 98 powdered infant formula (milk- and soy-based) samples and 155 infant cereal (barley-, rice-, oat-, wheat-, and mixed grain–based) products were collected from different retail locations in the United States over a 2-year period. OTA levels were determined by liquid chromatography–tandem mass spectrometry. Although OTA was not detected in any of the infant formula samples, 47 (30%) of 155 infant cereals were contaminated with OTA in the range of 0.6 to 22.1 ng/g. At present, there is no regulatory limit for OTA in the United States. However, all of the positive samples were above the maximum level set by the European Commission (0.5 ng/g) for OTA in baby foods. OTA was detected in all types of infant cereals, but the highest incidence and concentrations were found in oat-based infant cereals (59%), followed by mixed grain cereals (34%). Increased surveillance and monitoring of OTA levels in grains used in infant foods may be needed to reduce exposure of infants and young children to OTA from cereal products. [ABSTRACT FROM AUTHOR]

Pesticides are one of the only chemical contaminants that are purposefully introduced to the environment in large quantities. After application to crops, pesticides can be volatilized into the atmosphere and undergo medium to long-range transport. Through wet deposition, pesticides can be removed from the atmosphere far from their initial application site, posing a variety of environmental and health hazards, such as toxicity to terrestrial and aquatic species, crop damage, and poor air quality. Identifying pesticides and their degradation products in wet deposition is crucial to understanding how they are transported in the atmosphere. High-resolution mass spectrometry is a useful tool to carry out suspect screening on complex mixtures. However, suspect screening for pesticides in atmospheric waters is lacking. In this work, liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC-QToF-MS) is used for the first time to screen for suspect pesticides in wet deposition. The composition of precipitation samples collected in the central United States from 2018 to 2021 was screened against a library of thousands of compounds, and the presence of 23 pesticides was confirmed using reference standards, including common herbicides such as atrazine, metolachlor, and alachlor, as well as three species that had never before been quantified in wet deposition: diphenamid, octhilinone, and desthio-prothioconazole. A significant increase in the deposition flux of many pesticides was observed at the start of planting season, suggesting local agricultural sources to the atmosphere. In addition, pesticides not commonly used locally were also detected, suggesting regional atmospheric transport. Using statistical analyses and air mass back trajectory calculations, the seasonal trends, physicochemical properties, and potential origins of pesticides were examined. Overall, this work highlights the power of liquid chromatography high-resolution mass spectrometry for identifying both known and unexpected pesticides in precipitation, allowing for more accurate modeling of the atmospheric transport and fate of these compounds. [Display omitted] • Analyzed wet deposition by liquid chromatography high-resolution mass spectrometry. • First application of LC-HRMS for suspect screening of contaminants in precipitation. • Identified 23 pesticides and degradates, with deposition fluxes of 0.33–102 μg m−2 • Strong seasonal trends for locally-used herbicides in the central United States. • Air mass back trajectories support regional atmospheric transport of pesticides. [ABSTRACT FROM AUTHOR]