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• First established reference intervals for estradiol using a UHPLC-MS/MS-based method in South Korea. • Serum samples from 634 pediatric patients, including neonates, infants, children, and adolescents. • The highly analytical sensitive UHPLC-MS/MS method was useful for estradiol determination in children. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) is a reliable and accurate method for measuring steroid hormone levels. There is an increasing need for sensitive and precise methods to measure estradiol in pediatric patients. Here, we established reference intervals for estradiol in healthy children using a UHPLC–MS/MS-based method for the first time in South Korea. Serum estradiol was measured using a Sciex Triple QuadTM 6500 + UHPLC–MS/MS (Sciex, Framingham, MA, USA). Reference intervals for estradiol were established according to the CLSI document EP28-A3c:2008. The reference intervals were validated using serum samples from 634 pediatric patients, including neonates, children, and adolescents. Among them, 389 specimens were used in analysis of the specimen acceptance time. Statistical analysis was performed using MedCalc (MedCalc, Ostend, Belgium) and Analyse–it (Analyse–it Software Ltd., Leeds, United Kingdom) software. Reference intervals for boys (n = 297) were <16.6, <7.3, <19.0, <30.5, 7.6–96.5, and 10.6–134.4 pmol/L among those aged <1, 1–5, 6–9, 10–11, 12–14, and 15–17 years, respectively. Reference intervals for girls (n = 337) were <114.7, <24.2, <34.8, 8.0–177.0, 10.4–480.5, and 9.1–486.7 pmol/L among those aged <1, 1–5, 6–9, 10–11, 12–14, and 15–17 years, respectively. Overall, there was no effect of specimen acceptance time on estradiol measurements in boys or girls, except for that in the group aged 10–11 years. The reference intervals for healthy children were validated using a UHPLC–MS/MS-based method. The highly analytical sensitive UHPLC–MS/MS method may be useful for estradiol determination in pediatric patients. [ABSTRACT FROM AUTHOR]

• We established an LC–MS/MS method to simultaneously quantify tegoprazan and its major metabolite Ml. • Developed method was based on protein precipitation and LC–MS/MS analysis, and it was well validated. • The method was successfully applied to a single dose pharmacokinetic study in dogs. Tegoprazan is a novel potassium-competitive acid blocker (P-CAB) recently approved in Korea as a next-generation therapeutics for gastric acid-related diseases. In the present study, we demonstrate a simple bioanalytical liquid chromatography/tandem mass spectrometry (LC–MS/MS) method for the simultaneous quantification of tegoprazan and its major metabolite (M1) in dog plasma. The developed method is based on protein precipitation and LC–MS/MS, validated according to the regulatory guidance for bioanalytical method validation. The calibration curves were linear in the concentration range of 50 ng/mL–50 μg/mL and 5 ng/mL–5 μg/mL for tegoprazan and M1, respectively. The inter- and intra-day precisions were evaluated with a coefficient of variation of <15%, and the mean accuracy ranged 92.6%–105%. The method exhibited good sensitivity and specificity. The stability of bench-top (for 8 h), freeze–thaw (3 cycles), and processed-samples (for 24 h at 4 °C) was acceptable. Tegoprazan was stable in dog plasma for 6 weeks at −70 °C. In conclusion, we successfully established a method for the simultaneous quantification of tegoprazan and M1 in dog plasma, and the method was validated for specificity, sensitivity, linearity, matrix effects, recovery, accuracy, precision, and stability. Finally, we show that the method was successfully applied to a pharmacokinetic study in dogs. [ABSTRACT FROM AUTHOR]

• Metabolic profiles of BZYQT in rats were systematically characterized. • Flavonoids and triterpenoids of BZYQT showed the higher MS response in rat plasma. • Proposed metabolic pathways of atractylenolide III in rats were first explored. • BZYQT-related components underwent massive phase I and II metabolism in rats. • A total of 162 BZYQT-related xenobiotics were detected in rats biosamples. Bu-Zhong-Yi-Qi-Tang (BZYQT), a famous traditional Chinese medicine prescription (TCMP), has been extensively used for conditioning sub-health status and diseases caused by spleen-qi deficiency in China for over 700 years. BZYQT is prevalent not only in China, but also in Japan and South Korea for the clinical treatment of chronic diseases, such as fatigue, tuberculosis and loss of appetite after surgery. However, due to a lack of research on the holistic metabolism of BZYQT, the in vivo bioactive components of BZYQT remain unclear, hindering further study of its in vivo mechanism of action and quality control. In the present study, a four-step integrated strategy based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS) was established to systematically screen the in vivo xenobiotics of BZYQT. Ultimately, a total of 162 xenobiotics (59 prototypes and 103 metabolites) were identified or tentatively characterized, including 48 in plasma, 147 in urine and 58 in feces, while the in vivo metabolic profile of atractylenolide III (a major component of BZYQT) was elucidated for the first time. The xenobiotics of BZYQT mainly included flavonoids from Astragali Radix , Glycyrrhizae Radix et Rhizoma and Citrus reticulatae Pericarpium ; lactones from Angelicae Sinensis Radix and Atractylodis Macrocephalae Rhizoma ; and triterpenoid saponins from Cimicifugae Rhizoma. After oral administration, BZYQT-related components underwent diverse metabolic pathways. Among them, flavonoids mainly underwent glucuronidation, sulfation and demethylation, while lactones mainly underwent hydroxylation and acetylcysteine conjugation, and deglycosylation was the major metabolic reaction of saponins. Our investigation gives a comprehensive analysis of the metabolic characteristics of BZYQT and will provide an important basis for further studying the pharmacokinetics of BZYQT to explore its in vivo disposal features and discover its in vivo bioactive components. [ABSTRACT FROM AUTHOR]

In this study, we aimed to establish a method for determination of multiple mycotoxins such as aflatoxins, ochratoxin A, and zearalenone in red pepper powder samples based on the quick, easy, cheap, effective, rugged, and safe (QuEChERS) approach for extraction and cleanup, with detection and quantification by high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) in both positive- and negative-ion modes. The developed LC-MS/MS analytical method was compared with an enzyme-linked immunosorbent assay (ELISA) to improve the reliability of our developed method. The linearity, precision, and accuracy were validated for the LC-MS/MS methods. The results obtained with the LC-MS/MS were linear, with a correlation coefficient (R2) of >0.998. The limits of detection and quantification for mycotoxins were 0.07 to 0.71 μg/kg and 0.20 to 1.81 μg/kg, respectively. Intra- and interday precision tests (expressed as the relative standard deviation) for each analyte were 1.58 to 5.97% and 0.97 to 9.01%, respectively. Average recoveries were 85.70 to 94.99%. The validation results for the ELISA were linear (R2 > 0.995), and recoveries were 77.13 to 93.93%. Both analytical methods were applied to determine the presence of mycotoxins in commercial red pepper powder samples from South Korea. Four of the total 56 samples were contaminated with aflatoxins, and 6 samples were contaminated with ochratoxin A; these results were consistent for the two methods (P > 0.05). Therefore, our developed LC-MS/MS with QuEChERS approach for determination of multiple mycotoxins may be useful for controlling the quality and safety of red pepper powder. [ABSTRACT FROM AUTHOR]

The number of glyphosate intoxication cases has been increased after the regulation of paraquat. Unfortunately, there are no reports on the potential concentration of glyphosate for those acute intoxicated patients admitted to emergency rooms and the correlation between the concentration of glyphosate and clinical symptoms in Korea up to our knowledge. As a nonselective herbicide, analysis of glyphosate requires derivatization because of its amphoteric and strongly polar nature. In order to develop a method to determine the concentration of glyphosate and its metabolite, aminomethylphosphonic acid (AMPA) in blood samples without derivatization, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was utilized with a hydrophilic interaction chromatography (HILIC) column. The validation of this method showed that the limits of detection (LODs) and limits of quantitation (LOQs) for glyphosate and AMPA were 50 and 100ng/mL, respectively. In addition, matrix effect, recovery rate, and accuracy and precision in intra and inter-day were evaluated during the validation study of this method. Blood samples acquired from five glyphosate intoxicated patients were analyzed to investigate the correlation between the concentration of glyphosate and clinical symptoms. These patients were previously admitted to the emergency room at a University Hospital in Korea after glyphosate was self-administered in suicide attempts or by accident. As results of blood sample study, the concentration of glyphosate and AMPA were found in the range of 1.0-171.1 and 0.2-2.6μg/mL, respectively. The concentration ratio of glyphosate to AMPA was 55-71. According to the clinical reports for those patients, they were in the age between 47 and 82 years old and administered about 50-400mL. The blood samples were collected within 2-5h after administration of glyphosate. Among the intoxicated patients, the most common clinical symptom was metabolic acidosis, identified in four patients. The comparison between the concentration of glyphosate and administered dosage did not show the correlation, which suggests further investigation on the effects of surfactants in glyphosate from different vendors. [ABSTRACT FROM AUTHOR]

• First report of clinical pharmacokinetic study of Banhahoobak-tang tablets. • First report of in vitro analysis for 18 main components of Banhahoobak-tang. • Provide scientific evidence for clinical use of Banhahoobak-tang. • Serve as a basis for designing dosage forms of Banhahoobak-tang tablets. • Useful for effectiveness, safety, and quality evaluation of Banhahoobak-tang tablets. Banhahoobak-tang is the most prescribed herbal drug in East Asia when individuals experience sudden symptoms such as sore throat or neurological symptoms. The low toxicity and high in-vivo safety of this herbal medicine has made it more attractive to patients, and it has recently been formulated as tablets. In addition, Banhahoobak-tang tablets are registered as health insurance drugs in South Korea, and clinical prescriptions and demand are increasing. However, there are very few clinical trial data as well as very little accurate content analysis and results for Banhahoobak-tang tablets. The purpose of this study was to perform in-vitro and in-vivo studies on Banhahoobak-tang tablets, including content analysis, pharmacokinetics in humans, and plasma protein binding. For this study, a UPLC-ESI-MS/MS method with polarity switching was developed for simultaneous analysis of 18 components of Banhahoobak-tang. To separate the analytes, a C 8 reverse-phase column was used as the stationary phase, 0.1 % aqueous formic acid and acetonitrile as the mobile phase, and ionization and multiple reaction monitoring for quantification. The developed method was able to isolate and quantify the 18 components with good sensitivity and selectivity and was fully validated according to international analytical standards. Stability tests were also conducted on the analytes. Finally, the method was applied to in-vitro and in-vivo studies of Banhahoobak-tang tablets, and the tablet components were 52.49 ng/g to 91.00 μg/g on average. The detected components showed rapid oral absorption in humans as well as high plasma protein binding ratio overall. These results and methods can be useful not only for effectiveness and safety evaluation but also for quality control of Banhahoobak-tang tablets. [ABSTRACT FROM AUTHOR]

• LC–MS/MS for plasma donepezil, 6- O -desmethyl donepezil, and spinosin was developed. • The simultaneous assay was rapid and efficient with a small beagle plasma volume. • The assay showed excellent performance and advantages over existing assays. • The assay was successfully applied to pharmacokinetics of DHP1401 with Aricept®. Spinosin, which is traditionally used for sedation and sleep disorders, has recently shown potential effects in alleviating memory loss. As spinosin is the main bioactive component in a standardized dried 50% ethanol extract of the seeds of Zizyphus jujuba var. spinosa , a Phase IIb clinical trial is ongoing, in Korea for the combination of the above extract formulated in a tablet (DHP1401 tablet) with donepezil hydrochloride (Aricept® tablet) in patients with mild to moderate Alzheimer's disease. Therefore, to promote safety and efficacy evaluations, a reliable method for the simultaneous detection and analysis of the two drugs is needed. Toward this end, in this study, we established and validated a rapid and sensitive LC–MS/MS method for the simultaneous determination of donepezil, its pharmacologically active metabolite 6- O -desmethyl donepezil, and spinosin in beagle dog plasma (50 μL). After optimization of the system, we used methanol for simple protein precipitation. Chromatographic separation was performed using a Phenomenex Luna C 18 column (100 × 2.0 mm, 3 μm) with a mobile phase consisting of 0.1% formic acid in acetonitrile-0.1% formic acid in distilled water (2:8, v/v) at a flow rate of 0.65 mL/min. All analytes were detected and quantified in selected reaction monitoring mode. All calibration curves showed good linearity (r ≥ 0.9965) over the concentration range of 0.02–20, 0.02–10, and 0.5–250 ng/mL for donepezil, for 6- O -desmethyl donepezil, and spinosin, respectively. This validated method was then successfully applied to a pharmacokinetic study in beagle dogs with no evidence for potential drug–drug interactions between DHP1401 and donepezil hydrochloride. This information and optimized assay can be useful for the anticipated co-administration of these two drugs in clinical settings. [ABSTRACT FROM AUTHOR]

• The levels of PFAS in the multimedia environment of Asan Lake area were examined. • PFOA in air and soil, PFPeA in water, and PFOS in sediment and fish were majors. • Long-chain PFAS were dominant PFAS in most media except water. • Longer-chain PFAS, especially PFOS, are significantly accumulated in fish. • PCA result implies that PFAS in fish might be transferred from the sediment. Seasonal and spatial variations in per- and polyfluoroalkyl substances (PFAS) concentrations in different environmental media in the Asan Lake area of South Korea were investigated by measuring liquid chromatography-tandem mass spectrometry (LC–MS/MS). The mean concentrations of Σ 16 PFAS in the different media were in the ranges of 20.7–98.2 pg/m3 in air, 17.7–467 ng/L in water, 0.04–15.0 ng/g dry weight (dw) in sediments, and not detected (n.d.)–12.9 ng/g dw in soils, and the mean concentrations of Σ 19 PFAS in fish ranged from n.d. to 197 ng/g wet weight. The most frequently detected PFAS were perfluorooctanoic acid (PFOA) in air and soils, perfluoropentanoic acid (PFPeA) in water, and perfluorooctane sulfonate (PFOS) in sediment and fish. Long-chain PFAS species dominated over short-chain PFAS in most media samples except for the water phase. Sediment-water partition coefficients (log K d) and bioaccumulation factors (log BAF) of PFAS were calculated using measured concentrations in water, sediments, and fish. Log K d of PFAS tended to increase with increasing CF 2 units of PFAS, and perfluorodecanoic acid (PFDA) and PFOS showed the highest log BAF value (> 3.0) in all fish species. These results indicate that longer-chain PFAS, especially PFOS, can be effectively accumulated in biota such as fish. [ABSTRACT FROM AUTHOR]