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As a salt-type compound, mosapride citrate's metabolism and side effects are correlated with its salt-forming ratio. Several techniques were developed in this work to compare various quantitative nuclear magnetic resonance (qNMR) methodologies and to quantitatively examine the content of raw materials. Among the qNMR techniques, methods for 1H NMR and 19F NMR were developed. Appropriate solvents were chosen, and temperature, number of scans, acquisition time, and relaxation delay parameter settings were optimized. Maleic acid was chosen as the internal standard in 1H NMR, and the respective characteristic signals of mosapride and citrate were selected as quantitative peaks. The internal standard in 19F NMR analysis was 4,4′-difluoro diphenylmethanone, and the distinctive signal peak at −116.15 ppm was utilized to quantify mosapride citrate. The precision, repeatability, linearity, stability, accuracy, and robustness of the qNMR methods were all validated according to the ICH guidelines. By contrasting the outcomes with those from high-performance liquid chromatography (HPLC), the accuracy of qNMR was assessed. As a result, we created a quicker and easier qNMR approach to measure the amount of mosapride citrate and evaluated several qNMR techniques to establish a foundation for choosing quantitative peaks for the qNMR method. Concurrently, it is anticipated that various selections of distinct quantitative objects will yield the mosapride citrate salt-forming ratio. [ABSTRACT FROM AUTHOR]

Macadamia nuts are, economically, the second most important crop in the state of Hawai'i. A recent decline in yield and acreage has been attributed to insect damage and diseases such as Macadamia Quick Decline (MQD) caused by Phytophthora tropicalis and P. heveae. To develop an improved methodology for the diagnosis and treatment of MQD, investigations were undertaken to better understand the pathosystem of the disease. These investigations included sampling from multiple locations from sectioned trees utilizing two methods of tissue collection and isolations using two baiting techniques. The collection of tissue from the cambium and phloem of trees after scraping away the bark and in locations of recent or current sap exudation using a narrow diameter steel awl proved to be an efficient means for the molecular detection of the MQD pathogens from infected trees exhibiting MQD symptoms. In addition, a more efficient and cost-effective baiting method using apple puree was developed. [ABSTRACT FROM AUTHOR]

Solid‐phase peptide synthesis (SPPS) is the prevailing method for synthesizing research peptides today. However, SPPS is associated with a significant environmental concern due to the utilization of hazardous solvents such as N,N‐dimethylformamide (DMF) or N‐methylpyrrolidone, which generate substantial waste. In light of this, our research endeavors to identify more environmentally friendly solvents for SPPS. In this study, we have assessed the suitability of five green solvents as alternatives to DMF in microwave assisted SPPS. The solvents evaluated include Cyrene, ethyl acetate, 1,3‐dioxolane, tetrahydro‐2‐methylfuran, and N‐Butylpyrrolidinone (NBP). Our investigation encompassed all stages of the synthesis process, from resin swelling, dissolution of reagents, culminating in the successful synthesis of five diverse peptides, including the challenging ACP 65–74, Peptide 18A, Thymosin α1, and Jung‐Redemann peptide. Our findings indicate that NBP emerged as a strong contender, performing on par with DMF in all tested syntheses. Furthermore, we observed that combinations of NBP with either ethyl acetate or tetrahydro‐2‐methylfuran demonstrated excellent results. This research contributes to the pursuit of more sustainable and environmentally conscious practices in peptide synthesis. [ABSTRACT FROM AUTHOR]

In the present scenario, peptide is an emerging field of research having vast therapeutic applications. Diverse impurities may rise from various stages of the synthesis process and storage of the peptides. Because these contaminants may have an impact on the therapeutic safety and effectiveness of peptides in their approaching applications, they must be identified and carefully monitored. Considering the pharmaceutical importance of the extent of peptides, we were motivated to synthesize a decapeptide and establish a novel gradient reversed‐phase high‐performance liquid chromatography (RP‐HPLC) method for its analysis along with efficient separation of its six related impurities. Different buffers, organic modifiers, and columns were used in the tests for good separation of these impurities. To establish a stability‐indicating method, a stress study was also conducted. The International Conference on Harmonization (ICH) guidelines have been followed for validation of the developed analytical method. The validated method revealed sufficient accuracy, specificity, linearity, robustness, precision, and high sensitivity for its intended use. The proposed method could be appropriate for routine analysis and stability assessment of the decapeptide, which might be useful for further scientific investigation. [ABSTRACT FROM AUTHOR]

Nitroimidazoles are well-known antibacterial and antiprotozoal agents, effective against various infections. However, they may also exhibit genotoxic, carcinogenic and mutagenic effects. This study aimed to develop an analytical method to quantify nitroimidazole residues and their metabolites in honey using Ultra Performance Liquid Chromatography coupled with Orbitrap High-Resolution Mass Spectrometry (UPLC-Orbitrap-HRMS) and validate it according to Commission Implementing Regulation (EU) 2021/808. The method demonstrated limits of detection (LODs) ranging from 0.01 to 0.17 µg L−1 and limits of quantification (LOQs) from 0.020 to 0.29 µg L−1. Recovery rates ranged from 79.8% to 104%, with relative standard deviations (RSDs) between 4.2% and 19.6%. Analysis of 96 honey samples revealed nitroimidazole residues in 18.8% of them. These findings could enhance more effectively the Egyptian monitoring programs for these compounds in honey as to improve food safety. [ABSTRACT FROM AUTHOR]

An analytical method was developed for identification and quantification of zilpaterol in bovine liver, meat, heart, and kidney, using liquid chromatography coupled to quadrupole-Orbitrap high-resolution mass spectrometry (LC-Q-Orbitrap HRMS). It was validated in accordance with Commission Implementing Regulation (CIR) EU 2021/808 at six different concentrations, ranging from 0.1 to 5 μg/kg. The mean recoveries ranged from 71% to 99%, while the decision limit (CCα) and detection capability (CCβ) ranges were 0.11–0.12 μg/kg and 0.13–0.15 μg/kg, respectively. The method demonstrated good linearity (R2 > 0.9996) and the limits of detection (LODs) and of quantification (LOQs) were in the range of 0.015–0.061 μg/kg and 0.025–0.091 μg/kg, respectively. Out of 200 samples collected from local markets in Egypt, 17 contained zilpaterol residues. Liver samples revealed the highest detection frequency (26%), followed by meat (6%), at mean concentrations of 2.64 and 1.93 μg/kg, respectively. [ABSTRACT FROM AUTHOR]

Analysis of amatoxins is of great importance as these cyclic peptides contribute to a high number of fatalities each year. Development of analytical approaches needs to focus on rapid, sensitive, and reliable methods. By establishing an affinity column chromatography-based assay using the monoclonal amanitin antibody AMA9G3 and liquid chromatography (LC) coupled to high-resolution mass spectrometry (HRMS) for the trace detection of α-, β-, and γ-amanitin in human urine samples to confirm ingestion, we report the first approach that extents the current status of amatoxin analysis. The presented procedure allows detection of amatoxins in human urine down to 1 ng/mL. The method was successfully validated qualitatively for α- and γ-amanitin according to international recommendations. A proof of concept was performed by analyzing 37 urine samples after suspected amatoxin consumption submitted for regular clinical toxicological analysis. Using this antibody-based enrichment strategy, acute amatoxin intoxications can be determined within 90 min and due to the high sensitivity and selectivity, a comparable approach using target specific antibodies may also be used for other toxicological relevant peptides. [ABSTRACT FROM AUTHOR]

Background: Pralsetinib, a targeted inhibitor of the RET enzyme, plays a critical role in the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) characterized by RET gene fusion mutations following platinum-based chemotherapy. Nevertheless, impurities resulting from the manufacturing and degradation of pralsetinib have the potential to impact its therapeutic effectiveness and safety profile. Methods: To address this issue, a liquid chromatography method was developed and validated for the specific identification of pralsetinib and its related impurities. The separation of pralsetinib and its related impurities was achieved via a Waters X Bridge Ci8 column with dimensions of 4.6 mm x 250 mm and a particle size of 5 ^m. Mobile phase A was composed of 20 mmol/L potassium dihydrogen phosphate (KH2PO4) and acetonitrile (ACN) at a volume ratio of 19:1, while mobile phase B consisted solely of ACN, utilizing a gradient elution technique. Detection was performed at a wavelength of 260 nm, with an injection volume of 10 ^L and a flow rate of 1.0 mL/min. Results: The chromatographic method established in this study was validated according to the ICH Q2 (R1) guidelines. The method demonstrated excellent linearity over a specific concentration range (imp-A: 0.035-10.21 ^ig/mL; imp-B: 0.09-10.16 ^g/mL; imp-C: 0.15-10.19 μg/mL; pralsetinib: 0.04-10.32 ^g/mL). Additionally, the method possesses high sensitivity, with detection limits for impurities A, B, C, and pralsetinib of 0.01, 0.03, 0.015, and 0.013 ^g/mL, respectively, and quantification limits of 0.035, 0.09, 0.05, and 0.04 ^ig/mL, respectively. In terms of specificity, stability, repeatability, accuracy, and robustness, the method met the validation acceptance criteria. Overall, the chromatographic technique established in this study can effectively separate pralsetinib and its impurities, providing reliable assurance for the accurate detection and quantification of impurities. Conclusion: The chromatographic method developed in this study can be utilized for the detection of pralsetinib and its impurities, offering a crucial reference for research on the quality of pralsetinib. [ABSTRACT FROM AUTHOR]

Currently, the therapeutic potential of complex biomolecules such as peptides has significantly enhanced the demand for analytical method development and validation for their quality control. Peptides are more complex to analyze than small molecules because of their larger size and unique physical–chemical properties, which create different challenges for analytical method development. Reversed‐phase high‐performance liquid chromatography (RP‐HPLC) with ultraviolet or mass spectrometry is the most widely used technique for analyzing peptides and related substances. In the present study, a decapeptide and its six related possible impurities were synthesized in‐house and identified. A stability‐indicating RP‐HPLC method has been developed for the estimation of the decapeptide and its related substances. The developed method was validated according to the International Conference on Harmonization guidelines for specificity, linearity, limit of detection, quantification, accuracy, precision, and robustness. The stability‐indicating capability of the proposed method was studied under the stress conditions of acid, base, oxidative, thermal, humidity, and photolytic degradation. The decapeptide peak and its degradant were found to be homogeneous and pure in the studied stress trials, with mass balance for all types of degradation exceeding 95%. It confirms the reliability and appropriateness of determining the integrity and purity of the decapeptide and its related substances. [ABSTRACT FROM AUTHOR]

A new stability‐indicating RPHPLC method with short run time has been developed and validated for tofacitinib citrate and its related substances. The novel HPLC method integrates hydrophilic interaction liquid chromatography (HILIC) technology as the stationary phase and employs a mobile phase composed of phosphate buffer (pH 7.0) and acetonitrile (45:55, %v/v) at a flow rate of 0.5 mL/min under isocratic elution. Analytes were monitored via a UV detector at 210 nm and with the column oven temperature at 30°C for a 20‐min analysis. Precision (%RSD) for Impurity‐A and Impurity‐B and tofacitinib met specifications at 2.4%, 0.8%, and 0.0%, respectively. Accuracy ranged from 86% to 100% for impurities, with LOD at 0.03% and LOQ at 0.05%–0.06%. Correlation coefficients exceeded 0.999 for impurities and tofacitinib citrate. Solution stability was confirmed for 24 h at room temperature. The method range was extended from LOQ to ∼1.5% for impurities and LOQ to ∼150% for tofacitinib citrate. The method's stability was evaluated under acid and base hydrolysis, oxidative and water hydrolysis, and thermal and photolytic degradation. Introducing HILIC as the stationary phase for this work proved effective, eliminating the need of ion pair reagents, reducing analysis time, and ensuring consistent results. [ABSTRACT FROM AUTHOR]

Chlorthalidone and efonidipine hydrochloride are anti-hypertensive agents with different mechanisms of action. These drugs are generally used as monotherapy; however, recent study suggests their use in combination reduces the mortality rate. Based on this evidence, Zuventus Healthcare limited developed a combination dosage (Efnocar Ct) which has been recently approved for its use. Hence, a new, sensitive, precise and robust method was developed and validated to determine the purity of the compounds in bulk as well as tablet dosage forms. The HPLC analysis was achieved on Zobrax 150 column using acetonitrile and ammonium formate (60:40% v/v) as the mobile phase and the detection was achieved at a λ max of 248nm. The linearity was achieved between the concentration range of 3µg/ml - 18µm/ml for chlorthalidone and 10µg/ml - 60µg/ml concentration range for efonidipine hydrochloride. The % recovery for chlorthalidone was 100.03% and that for efonidipine was 100.24%, indicating the method to be accurate. The LOD and LOQ values for chlorthalidone was 0.01µg/ml and 0.02µg/ml and for efonidipine it was 0.26µg/ml and 0.88µg/ml. This indicates the sensitivity of the method. Robustness studies have shown no significant variations and degradation studies have shown acceptable results. The results of the proposed method for linearity, accuracy, sensitivity and robustness were within the acceptable limits. [ABSTRACT FROM AUTHOR]

Effect concentrations of ammonia, nickel, sodium chloride, and potassium chloride from short‐term 7‐day tests were compared to those from standard chronic 28‐day toxicity tests with juvenile mussels (fatmucket, Lampsilis siliquoidea) to evaluate the sensitivities of the 7‐day tests. The effect concentrations for nickel (59 µg Ni/L), chloride (316–519 mg Cl/L, a range from multiple tests), and potassium (15 mg K/L) obtained from the 7‐day tests were within a range of effect concentrations for each corresponding chemical in the 28‐day tests (41–91 µg Ni/L, 251–>676 mg Cl/L, 15–23 mg K/L), whereas the 7‐day ammonia effect concentration (0.40 mg/L total ammonia nitrogen; TAN) was up to 3.3‐fold greater than the 28‐day effect concentrations (0.12–0.36 mg TAN/L) but with overlapped 95% confidence limits. These results indicate that the 7‐day tests produced similar estimates compared to the 28‐day tests. Further studies are needed to evaluate the 7‐day test sensitivity using additional chemicals with different modes of toxic action. Environ Toxicol Chem 2024;43:2020–2025. Published 2024. This article is a U.S. Government work and is in the public domain in the USA. [ABSTRACT FROM AUTHOR]

A simple, selective, and economical UV spectrophotometric method has been developed using ethanol as solvent (50%) to determine the umifenovir content in bulk and pharmaceutical dosage formulations. At a pre-determined λ max of 260 nm, it has shown linear in the 10-50 µg/mL range and exhibited a good correlation coefficient (R² = 0.9927) and excellent mean recovery (98.00--104%). The method was validated statistically, and recovery studies were done for linearity, precision, and accuracy. The obtained results proved that the method can be employed for the routine analysis of umifenovir in bulks and commercial formulations. [ABSTRACT FROM AUTHOR]

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From organs to subcellular organelles, trace element (TE) homeostasis is fundamental for many physiological processes. While often overlooked in early stages, manifested TE disbalance can have severe health consequences, particularly in the context of aging or pathological conditions. Monitoring TE concentrations at the mitochondrial level could identify organelle-specific imbalances, contributing to targeted diagnostics and a healthier aging process. However, mitochondria isolation from frozen tissue is challenging, as it poses the risk of TE losses from the organelles due to cryodamage, but would significantly ease routine laboratory work. To address this, a novel method to isolate an enriched mitochondria fraction (EMF) from frozen tissue was adapted from already established protocols. Validation of manganese (Mn), iron (Fe), and copper (Cu) quantification via inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) showed sufficiently low quantification limits for EMF TE analysis. Successful mitochondrial enrichment from frozen liver samples was confirmed via immunoblots and transmission electron microscopy (TEM) revealed sufficient structural integrity of the EMFs. No significant differences in EMF TEs between frozen and fresh tissue were evident for Mn and Cu and only slight decreases in EMF Fe. Consequently, EMF TEs were highly comparable for isolates from both tissue states. In application, this method effectively detected dietary differences in EMF Fe of a murine feeding study and identified the disease status in a Wilson disease rat model based on drastically increased EMF Cu. In summary, the present method is suitable for future applications, facilitating sample storage and high-throughput analyses of mitochondrial TEs. [ABSTRACT FROM AUTHOR]

Background and Aims: Delamanid is an active drug substance used in efficient treatment for multidrug-resistant tuberculosis (MDR TB). A straightforward, accurate, and precise HPTLC technique has been developed and validated for the study of the delamanid. Methods: The samples were placed as bands on an aluminium TLC plate covered with silica gel. Delamanid was completely separated using ethyl acetate and n-hexane as the mobile phase; the RF value was 0.51 0.098. At 330 nm, densitometric detection was performed in the absorbance mode. This method led to the discovery of sharp, symmetrical, and well-defined peaks. Results: A linear correlation was obtained for the concentration range of 200–1200 ng/spot, with a determination coefficient of 0.992. According to the requirements set out by the International Conference on Harmonisation, the method’s accuracy, recovery, repeatability, and robustness were all validated. The limit of quantitation was determined to be 349.11 ng/spot, whereas the lowest detectable level was found to be 115.2 ng/spot. This approach permitted the analysis of delamanid in the presence of their degradation products created under various stress conditions, according to the findings of the validation research. delamanid degraded by 20.54% and 35.72% under alkaline and photodegradation conditions, respectively. Conclusion: The established method might be used to evaluate the stability of delamanid in a commercial pharmaceutical dose form. Regarding HPTLC-induced degradation of delamanid, no prior technique has been documented. This technique was successfully used to quantify the amount of delamanid in its commercially available formulation. [ABSTRACT FROM AUTHOR]

Simultaneous determination of a tandem of drugs like perindopril and rosuvastatin with differences in water and organic solvent solubilities, hydrophobicity, polarities, and UV‐absorbing possibilities between them necessitates careful selection of chromatographic conditions. The four specified and different bonded reversed‐phase columns were tested with running mobile phases containing various composition contents concepts; the concept of using diluted trifluoroacetic acid in mobile phase composition with acetonitrile enabled simultaneous acidification and weak ion‐pairing with protonized molecules of analytes, yielding appropriate, short, reasonable run times and resolutions of analytes, satisfying UV‐transparency, and good peak symmetries. These facts especially stand for the peak of perindopril, as a member of the group of proline‐containing moiety in its structure, often and easily prone to peak‐tailing, skewing, or splitting on the high‐performance liquid chromatography chromatograms, which is usually solved by using alkyl‐sulfonate base and ion pairs on higher concentrations of buffering salts with low pH values and with column temperatures increasing by 50°C–60°C. Linearity range was 0.002/004–0.5 mg/mL. The score for method AGREE was 0.73–0.77. The method development approaches, with all columns employing our concepts in mobile phases and experimental conditions, can cover the complete needs and demands of quality control departments and laboratories as simple high‐throughput analysis methods. [ABSTRACT FROM AUTHOR]

Mexiletine (MEX) is an antiarrhythmic drug used to treat acute and chronic ventricular arrhythmias. A simple isocratic, rapid, specific, stability‐indicating, and sensitive reverse‐phase ultra‐high‐performance liquid chromatography (UHPLC) method was developed and successfully validated to quantify the assay and impurities of MEX hydrochloride. The new UHPLC method showed the optimum separation of MEX and its seven impurities in 20 min by using sodium acetate buffer (0.14 mM) with 0.3% of glacial acetic acid (pH 4.8) and methanol in the ratio of 40:60 (v/v) as mobile phase. The method used an Acquity HSS T3 (100 × 3.0 mm, 1.8 µm) chromatographic column at a 0.2 mL/min flow rate. The injection volume is 2 µL, and 254 nm is the detection wavelength. Note that, 25°C is the column oven temperature. The method is linear over the concentration range of the quantification limit (0.03%) to 150% (0.3%) of the specification level (0.2%) for the impurities and 50%–150% for the assay method. The quality control lab of bulk drugs and finished dosage form successfully applied the new UHPLC method for quantification of assay and impurities of MEX hydrochloride. [ABSTRACT FROM AUTHOR]

In order to improve and replace the enantiomer method outlined in the olodaterol hydrochloride draft monograph (From the European Pharmacopoeia forum), one new, simple, and fast enantioselective normal phase high‐performance liquid chromatography chiral method was developed on polysaccharide‐based Chiral MX (2) (4.6 × 250 mm, 5 μm) column. n‐Hexane, ethanol, and diethylamine in the ratio of 40:60:0.1 (V/V/V) were selected as mobile phase at a flow rate of 0.8 mL/min, and the detection was performed on a photodiode array detector at 225 nm with 5 μL injection volume. The column temperature was set at 40°C for better peak shape and sensitivity. The analysis time can be shortened to 15 min, whereas the resolution between enantiomer and olodaterol was found to be even more than 10.0, which was far better than that obtained with the reported method in this draft monograph. The developed chiral method was validated in accordance with ICH Q2 (R1), including specificity, LOD&LOQ, precision, linearity, accuracy, and robustness. Thereby, the proposed method was demonstrated to be suitable for the determination of enantiomer in olodaterol hydrochloride bulk drug and drug product. Besides, the thermodynamic parameters were evaluated on the basis of Van't Hoff plots that was used to explain correlative chiral recognition mechanisms with the chiral stationary phase. [ABSTRACT FROM AUTHOR]

Indacaterol, glycopyrronium, and mometasone furoate triple combination inhalable fixed-dose medicines are effectively used to treat asthma and various chronic pulmonary disorders. The study aimed to develop and validate a simple single-run RP-HPLC impurity quantitation method. The chromatographic separation was accomplished using gradient elution mode of mobile phase A (potassium dihydrogen phosphate buffer pH 2.2) and mobile phase B (mixture of acetonitrile and methanol), with a flow rate of 0.8 mL/min using YMC Triart, C18 (250 × 4.6 mm, 5 µm) HPLC column at 45 °C and the detection wavelength of 210 nm (for indacaterol, glycopyrronium and their impurities) and 248 nm (for mometasone furoate and its impurities). Water and methanol (20:80) were used as a diluent. Quantitation of 10 known and several unknown impurities was successfully performed with the determination of relative response factors for all the known impurities. The developed method was validated as per the ICH Q2(R1) guidelines. The stability indicating the nature of the method was proved by performing stress study on the sample and placebo. The linearity and range of the method were proved by calculating the r2 values (> 0.998). The overall precision was found to be within 1.82 − 7.76% RSD. The recovery for all the actives and known impurities were within 90 − 115% with 0.4 − 12% RSD. The sample solution was stable for 2 days at room temperature. The developed method can be successfully used for the impurity analysis of routine, stability, and commercial samples in a quality control laboratory of the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Abstract Analysis of amatoxins is of great importance as these cyclic peptides contribute to a high number of fatalities each year. Development of analytical approaches needs to focus on rapid, sensitive, and reliable methods. By establishing an affinity column chromatography-based assay using the monoclonal amanitin antibody AMA9G3 and liquid chromatography (LC) coupled to high-resolution mass spectrometry (HRMS) for the trace detection of α-, β-, and γ-amanitin in human urine samples to confirm ingestion, we report the first approach that extents the current status of amatoxin analysis. The presented procedure allows detection of amatoxins in human urine down to 1 ng/mL. The method was successfully validated qualitatively for α- and γ-amanitin according to international recommendations. A proof of concept was performed by analyzing 37 urine samples after suspected amatoxin consumption submitted for regular clinical toxicological analysis. Using this antibody-based enrichment strategy, acute amatoxin intoxications can be determined within 90 min and due to the high sensitivity and selectivity, a comparable approach using target specific antibodies may also be used for other toxicological relevant peptides.

This study describes the dissolution release profiles of nicotine and flavor markers from three loose moist smoke-less tobacco (MST) products, same brand, each made with a distinct flavor. The US Pharmacopeia flow-through cell dissolution apparatus 4 (USP-4) was employed, following a previously published method that was validated to study the nicotine release from MST products. Herein, we expanded the scope of the analytical method by incorporating three flavor markers including methyl salicylate, ethyl salicylate, and glycyrrhizic acid to provide an understanding of the dissolution release profiles of not only nicotine but also of flavor markers. The dissolution release profiles of nicotine were found to be equivalent across all three tobacco products. In contrast, the release profiles of the studied flavor markers exhibited distinct differences, primarily influenced by their chemical properties, particularly polarity. Notably, glycyrrhizic acid demonstrated the most rapid release rate, while ethyl salicylate exhibited the slowest release rate. This study serves as a valuable resource for researchers, manufacturers, and regulatory bodies involved in the evaluation of MST products attributes and performance.

Liquid chromatography-mass spectrometry (LC-MS) is the key technique for analyzing complex lipids in biological samples. Various LC-MS modes are used for lipid separation, including different stationary phases, mobile-phase solvents, and modifiers. Quality control in lipidomics analysis is crucial to ensuring the generated datas reliability, reproducibility, and accuracy. While several quality control measures are commonly discussed, the impact of organic solvent quality during LC-MS analysis is often overlooked. Additionally, the annotation of complex lipids remains prone to biases, leading to potential misidentifications and incomplete characterization of lipid species. In this study, we investigate how LC-MS-grade isopropanol from different vendors may influence the quality of the mobile phase used in LC-MS-based untargeted lipidomic profiling of biological samples. Furthermore, we report the occurrence of an unusual, yet highly abundant, ethylamine adduct [M+46.0651]+ that may form for specific lipid subclasses during LC-MS analysis in positive electrospray ionization mode when acetonitrile is part of the mobile phase, potentially leading to lipid misidentification. These findings emphasize the importance of considering solvent quality in LC-MS analysis and highlight challenges in lipid annotation.

Ruxolitinib is a Janus Kinase 1 and 2 inhibitor drug that was designated by the Food and Drug Administration (FDA) in 2011 as a treatment for myelofibrosis with moderate to high risk. Ruxolitinib has instability to light that can cause a decrease in levels. The aim of this research is to obtain a selective, accurate and precise analytical method to determine levels and determine the stability of ruxolitinib. Determination of optimum RP-HPLC conditions from the development of analytical methods with variations in mobile phase composition, flow rate, buffer concentration and buffer pH. The new analytical method determines ruxolitinib levels by RP-HPLC using a C18 Hypersil ODS column, wavelength 310 nm, mobile phase composition acetonitrile: H2O: citrate buffer (75:20:5), injection volume 20 μL, 0.10 M citrate buffer and pH 5.8. Calibration curve between ruxolitinib concentrations in the range of 1000-1800 μg/mL, correlation coefficient 0.9997. Accuracy 99.65%, repeatability precision 0.17%, interday precision 0.36%, LOD 26.48 μg/ml, and LOQ 88.26 μg/ml. The decrease in ruxolitinib levels after exposure to acids was 82.56%, bases were 88.01%, light was 69.06%, temperature was 75.29%. So it was concluded that the method resulting from method development and validation met the validation criteria, determining ruxolitinib levels showed exposure to unstable acids, bases, temperature and light. [ABSTRACT FROM AUTHOR]

This work was aimed at creating a new, fast, and accurate UV spectrophotometric method for quantifying prazosin hydrochloride in pure and tablet dosage forms. A phosphate buffer solution of pH 6 was used as a diluent. The highest absorbance of prazosin hydrochloride was measured at 247 nm, and the linearity ranged from 2 to 8 μg/mL. The regression equation for prazosin hydrochloride was y= 0.087x + 0.236, with a correlation value 0.987. The percentage of recovery ranged from 99.6 to 101%. The relative standard deviation for intraday precision and interday precision was determined to be less than 2. The LOD and LOQ of prazosin hydrochloride were determined to be 0.0375 and 0.113 μg/mL, respectively. International Council for Harmonisation criteria validated the spectrometric technique and was suitable for routine quantitative measurement of prazosin hydrochloride in pure and tablet dosage forms. [ABSTRACT FROM AUTHOR]

Background: Ketamine is an NMDAR antagonist with aggregating use across many areas of medicine. P450 enzymes heavily metabolise ketamine, where norketamine is a first pass formed metabolite following initial N-demethylation. Serum ketamine monitoring is becoming increasingly important, requiring a sensitive method with a robust lower limit of quantitation. Methods: Samples were prepared using protein precipitation or solid phase extraction. Ion suppression was investigated to optimise sample preparation technique, followed by reverse-phase chromatography coupled with tandem mass spectrometry to analyse extractions using a Waters Xevo TQ-S Micro and associated Acquity chromatography systems. Performance characteristics were analysed to validate the assay. Results: Ketamine and norketamine retention times were 1.28 and 1.23 min, respectively. Ketamine and norketamine precursor ions fragmented into 2 distinguishable product ions (238.14 > 207.18/125.06 and 224.1 > 178.96/124.86). Performance characteristics include an assay recovery of 103.7% (ketamine) and 96.3% (norketamine), lower limit of quantitation 36.2 µg/L (ketamine) and 38.9 µg/L (norketamine), and intra-assay imprecision ≤ 7.04% on average. Conclusions: A robust and reproducible assay with limited sample preparation has been designed and validated. The linearity of the assay covers all ranges of interest reported in the literature. Ion suppression was clearly reduced via use of solid phase extraction. The method will form the basis of ketamine monitoring and providing valuable patient information on tolerance and metabolism. [ABSTRACT FROM AUTHOR]

A sensitive spectrofluorimetric method was developed to determine trazodone hydrochloride in its formulation and urine sample. The principle of the developed method is based on the formation of an ion pair complex at a pH of 4.27 between the analyte drug and eosin Y, followed by its extraction into dichloromethane and subsequent fluorescence measurement. The fluorescence of the extracted trazodone-eosin Y complex was recorded at 450 nm with an excitation wavelength of 350 nm. Recording the fluorescence was utilized to construct the calibration plot, which was found to be linear in the range of 32.0–1.50 × 103 ng/mL of trazodone hydrochloride. The influences of experimental variables, namely pH, volumes of eosin Y (2.90 × 10–3 M), and buffer solution (pH 4.27), on the fluorescence intensity were examined and optimized by response surface methodology via Box−Behnken design. The limits of detection and the limit of quantitation of the reported method are 9.50 and 28.79 ng/mL, respectively. The accuracy of the proposed method was evaluated for intra-day and inter-day precision in the range of 0.46 to 0.77% RSD. The content of trazodone hydrochloride in its dosage forms was determined by the developed method using the standard addition technique, and the results showed good recovery between 96.50 and 99.25%, with a standard analytical error of 1.54 × 10–5 to 2.86 × 10–4. Interval hypothesis testing confirmed that it is lower than ±2%; hence, there was no bias between the developed and reference methods. No interference was observed from the common excipients present in tablet formulations. The developed method was also successfully applied for the determination of trazodone in urine samples, and recovery of the drug was observed in the range of 90–98%. [ABSTRACT FROM AUTHOR]

Summary: Herein, an ultra‐high performance liquid chromatography coupled to a diode array detector (UHPLC‐DAD) based quantification method has been developed for the simultaneous determination of 21 bioactive phenolic compounds present abundantly in food products. The developed method was validated in terms of parameters such as linearity, detection and quantification limits, intra‐day and inter‐day precision and recovery showing ideal results. Further, the developed method was applied for the quantitative analysis of phenolics in commercially procured dietary samples such as spices, green tea, black tea and dark chocolate. The major phenolics quantified in dry weight of different samples were epigallocatechin gallate (425.5 mg/10 g), epicatechin gallate (111.9 mg/10 g) in green tea; gallocatechin (286.8 mg/10 g) in dark chocolate; and naringin (93.9 mg/10 g) in star anise etc. Overall, the UHPLC‐DAD‐based method was found to be reliable, simple and specific for the estimation of phenolics in different targeted food samples. [ABSTRACT FROM AUTHOR]

Since the severe accident at Fukushima Daiichi Nuclear Power Plant, there has been an interest in the properties of oxide fuels in their near-melting temperature range. X-ray absorption fine structure (XAFS) is an effective method for understanding the fine structure and chemical bonding state of a sample; however, high-temperature XAFS measurements performed to date have been limited to 2000 K. We have developed a method for XAFS measurements of high-melting oxides above 2000 K. This method utilizes resistance heating of tungsten and confines the sample within a 0.06 mm slit to enable transmission-type XAFS measurements. We successfully performed an XAFS test with yttria-stabilized zirconia loaded at the tip of the slit and heated to 3000 K. [ABSTRACT FROM AUTHOR]

Mass spectrometry (MS) is a highly selective and sensitive analytical tool with a myriad of applications, but such techniques are typically used in laboratory settings due to the handling and preparations that are necessary. The merging of two streams of robust research, portable MS systems and next-generation ambient ionization methods, now provides the ability to perform high-performance chemical screening in an on-site and on-demand manner, with natural applications in disciplines such as forensic science, where samples of interest are typically found in field environments (i.e., traffic stops, crime scenes, etc.). Correspondingly, investigations regarding the suitability and robustness of these methodologies when they are utilized for authentic forensic evidence processing are prudent. This work reports critical insights into the role that choice of spray solvent system plays regarding analytical performance of two spray-based ambient ionization sources, paper spray ionization (PSI) and filter cone spray ionization (FCSI), when employed for evidence types containing emerging synthetic cannabinoids. The systematic characterization studies reported herein show that the applied spray solvent can dramatically affect both spectral intensity and signal duration, and in some circumstances, yield deleterious false negative responses. Overall, acetonitrile-based systems are shown to strike a balance between analyte solubility concerns and spray ionization dynamics of the novel ion sources employed on portable MS systems. [ABSTRACT FROM AUTHOR]

The retention behaviour of scopolamine (hyoscine) and its related compounds (norhyoscine, atropine, homatropine, and noratropine) was investigated on the silica-based HPLC stationary phase. The retention of investigated tropane alkaloids was interpreted by using the Soczewiński-Wachtmeister equation. A high correlation between the retention parameter (log k) and lipophilicity (log P) (R = 0.9923) confirms the significant influence of hydrophobic interactions on the retention behaviour of the aforementioned compounds. It was found that by increasing the acetonitrile fraction, a decrease in retention of the more polar epoxide derivatives (scopolamine, norhyoscine) and an increase in retention of the more lipophilic derivatives (atropine, noratropine, homatropine) is obtained. The best separation of the tropane alkaloids was achieved by a simple procedure that involved a mobile phase composed of acetonitrile and 40 mM ammonium acetate/0.05% TEA, pH 6.5; 50:50 v/v. Selected conditions were assumed for the determination of scopolamine hydrochloride in the eye drops (Scopolamini hydrobromidum 0.25%). The method was validated and it was found as selective, sensitive, precise, accurate, and robust for the further qualitative analysis of the scopolamine-related compounds. [ABSTRACT FROM AUTHOR]

Phosphine ligands are widely used in the manufacture of small molecule active pharmaceutical ingredients, for they play a key role in transition-metal-catalyzed cross-coupling. However, chromatographic analysis of phosphine ligands can be challenging because of the easily oxidizable nature of this class of compounds. This manuscript describes an out-of-specification (OOS) investigation study of XPhos raw material analysis by high performance liquid chromatography (LC). It is concluded that on-column degradation/oxidation is the culprit behind this OOS result. In addition, a slightly modified yet much improved new LC method is developed by adding a trace amount of tris(2-carboxyethyl)phosphine (TCEP) into the aqueous mobile phase. TCEP is also a phosphine compound and is commonly used as a reducing reagent in molecular biology. The trace amount of TCEP serves as a surrogate reagent to passivate the LC column and eliminate the on-column degradation/oxidation. As a result, a much more robust performance is achieved with greatly improved method precision and sensitivity. This is a general approach and can be applied to the LC analysis of many other phosphine ligands in the same manner. [ABSTRACT FROM AUTHOR]

The objective of this study was to develop a simultaneous analytical method for the determination of lignans, tocols, phytosterols, and squalene using high-performance liquid chromatography coupled with a diode array and fluorescence detector (HPLC-DAD-FLD). The method employed a VertisepTM UPS silica HPLC column (4.6 × 250 mm, 5 µm) with a mobile phase mixture of n-hexane/tetrahydrofuran/2-propanol. This approach enabled the simultaneous analysis of ten compounds within 22 min. The linear correlation (R2) exceeded 0.9901. The limit of detection (LOD) and limit of quantitation (LOQ) were up to 0.43 µg mL−1 for lignans and tocopherols and up to 326.23 µg mL−1 for phytosterol and squalene. The precision and accuracy of the intra-day and inter-day variation were less than 1.09 and 3.32% relative standard deviations (RSDs). Furthermore, the developed method was applied for the analysis of targeted compounds in twenty-eight sesame oil samples (1775–8965 µg g−1 total lignans, 29.7–687.9 µg g−1 total tocopherols, 2640–9500 µg g−1 phytosterol, and 245–4030 µg g−1 squalene). The HPLC method that has been developed was proven to be a reliable and effective tool for the determination of those functional compounds among sesame oil samples. [ABSTRACT FROM AUTHOR]

The high-value agarwood oil, largely used in perfumery is generally graded by the traditional method of sensorial assessment. The compositional complexity and variation made its quality control challenging. Besides, non-volatile contaminants and adulterants are the bottlenecks in gas-chromatographic detection. Herein, a HPTLC based technique was developed for the quality assessment of agarwood oil from Northeast India. A 'marker band' (anisylacetone and oxygenated sesquiterpene rich) on HPTLC profile, containing major peaks of the oil and characteristic agarwood aroma was quantified to assess the quality. The developed method was validated in terms of specificity, linearity, sensitivity, recovery and precision. The application of the method in test samples of three different grades indicated a positive correlation between 'marker band' quantity and oil quality. Its abundance in the superior grade oil was >50% and <20% in poor grade. It can be an efficient analytical tool for the quality assessment and grading of agarwood oil. [ABSTRACT FROM AUTHOR]

In the present investigation, an attempt was made for the development, validation, forced degradation and pharmacokinetic application of sitagliptin in the human plasma spiking studies by UV - HPLC method. The experimentation was developed based on the extensive literature survey and ascertained by the statistical parameters of the sampling. A simplified, accurate method was created by the liquid chromatographic system from Shimadazu LC 20AD consisting of manual injection. The optimized chromatogram was obtained with acetonitrile in the isocratic mobile phase method at a 1.0 mL/min flow rate. A thermo C-8 column (4.6X250mm,5μm) was used as a stationary phase, and 265.0nm was selected as the detection wavelength with the aid of a UV-Vis detector. The proposed method was validated as per ICH guidelines. The technique was linear in the range of 10-50μg/mL with correlation coefficient R2 = 0.9746, respectively. Recovery studies postulated that % RSD 19.14, 3 & 9.95 respectively. Injection repeatability values were found to be % RSD 17 & 10.63 for intraday and interday, respectively. Stress degradation studies revealed that sitagliptin degrades more rapidly when subjected to 0.1 NaoH. Human plasma spiking studies reported 3.02 ng/mL at 3.02+/-60 min of C and T max, respectively [ABSTRACT FROM AUTHOR]

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Sotorasib is a small molecule inhibitor and approved by USFDA for the treatment of non-small cell lung cancer (NSCLC). In the present study, forced degradation behavior of sotorasib was carried out by utilizing LC-MS/MS technique. As per ICH guidelines, the forced degradation is conducted in various conditions such as acidic, basic, oxidative, thermal and photolytic. A significant degradation was found in acidic, basic and oxidative conditions conversely sotorasib was found relatively stable in thermal and photolytic conditions. In acidic condition, two degradation products such as DP1 and DP3 were isolated. Also, DP3 is the common degradant obtained in both acidic and basic conditions. DP2 is obtained from oxidative conditions. All the isolated degradation products are new and not reported in the literature. All the degradation products are completely characterized by IR, 1H NMR and mass spectroscopy. In conclusion, the scope of study will certainly useful in the regulatory requirements such as physiochemical stability of sotorasib, pharmacokinetic studies and clinical research related.

BackgroundPralsetinib, a targeted inhibitor of the RET enzyme, plays a critical role in the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) characterized by RET gene fusion mutations following platinum-based chemotherapy. Nevertheless, impurities resulting from the manufacturing and degradation of pralsetinib have the potential to impact its therapeutic effectiveness and safety profile.MethodsTo address this issue, a liquid chromatography method was developed and validated for the specific identification of pralsetinib and its related impurities. The separation of pralsetinib and its related impurities was achieved via a Waters X Bridge C18 column with dimensions of 4.6 mm × 250 mm and a particle size of 5 μm. Mobile phase A was composed of 20 mmol/L potassium dihydrogen phosphate (KH2PO4) and acetonitrile (ACN) at a volume ratio of 19:1, while mobile phase B consisted solely of ACN, utilizing a gradient elution technique. Detection was performed at a wavelength of 260 nm, with an injection volume of 10 μL and a flow rate of 1.0 mL/min.ResultsThe chromatographic method established in this study was validated according to the ICH Q2 (R1) guidelines. The method demonstrated excellent linearity over a specific concentration range (imp-A: 0.035–10.21 μg/mL; imp-B: 0.09–10.16 μg/mL; imp-C: 0.15–10.19 μg/mL; pralsetinib: 0.04–10.32 μg/mL). Additionally, the method possesses high sensitivity, with detection limits for impurities A, B, C, and pralsetinib of 0.01, 0.03, 0.015, and 0.013 μg/mL, respectively, and quantification limits of 0.035, 0.09, 0.05, and 0.04 μg/mL, respectively. In terms of specificity, stability, repeatability, accuracy, and robustness, the method met the validation acceptance criteria. Overall, the chromatographic technique established in this study can effectively separate pralsetinib and its impurities, providing reliable assurance for the accurate detection and quantification of impurities.ConclusionThe chromatographic method developed in this study can be utilized for the detection of pralsetinib and its impurities, offering a crucial reference for research on the quality of pralsetinib.

Samarium diiodide (SmI2) is a single electron reductant and versatile synthetic tool that can be used to create carbon- carbon bonds or other synthetic transformations. SmI2 is typically used with an Argon atmosphere glovebox and anhydrous solvents from a solvent purification system; however, not all labs have access to these equipment. A more accessible air-free option is Schlenk line glassware. Here in reports an optimized method for the synthesis and use of SmI2 on a Schlenk line. During optimization of the system, it was found that the largest impact on the success of SmI2 was the THF solvent. Anhydrous solvent was achieved though distillation, but after storage of the solvent over two weeks enough moisture/air was accumulated to significantly impact the concentration of the SmI2 formed in solution. The use of molecular sieves further indicates that the impact of water accumulation in the solvent compared to oxygen has the most significant factor on the success of synthesizing SmI2. These observations of THF storage overtime are important to account for when carrying out SmI2 reactions and other air-sensitive reactions on the Schlenk line.