Bioanalysis最新文献

Aim: Branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) were suggested as potential biomarkers in liver disease. This study aimed to develop and validate a simple and rapid LC-MS/MS method to simultaneously measure serum BCAAs and AAAs levels in patients with liver injury, and further establish reference intervals of Chinese healthy adult populations.Patients & methods: Samples were prepared by a one-step protein precipitation and analysis time was 4 min per run.Results: The validation results showed good linearity (r² >0.9969), satisfactory accuracy (94.44% - 107.75%) and precision (0.10% - 5.90%).Conclusion: This method proved to be suitable for high-throughput routine clinical use and could be a valuable adjunct diagnosis tool for liver injury and other clinical applications.

There is growing evidence that various RNA molecules can serve as biomarkers for clinical diagnoses. Over the last decade, the high specificities and sensitivities of RNA biomarkers have led to proposals that they could be used to detect prohibited substances and practices in sports. mRNAs and circulating miRNAs have the potential to improve the detection of doping and expand the performance of the Athlete Biological Passport. This review provides a summary of the use of RNA biomarkers to detect human and equine doping practices, including a discussion of the use of dried blood spots as a stable matrix that supports and improves the general process of RNA biomarker detection. The advantages of RNA biomarkers over protein biomarkers are also discussed.

Aim: We aimed to develop a rapid and accurate LC-MS/MS method for determining the concentration of aloesone in rat plasma, and to investigate its pharmacokinetics. Methods: The rat plasma samples were extracted using acetonitrile. Chromatographic separation was achieved using a Kinetex XB-C18 column, with a mobile phase of methanol and water (containing 0.1‰ formic acid) in a gradient elution. An ESI source, operating in positive ion mode with multiple reaction monitoring, was utilized. Results & conclusion: The developed method meets all the requirements for methodological validation, and it was successfully applied in the pharmacokinetic study. It was observed that oral administration of aloesone in rats resulted in rapid absorption (time to reach C_max: 0.083 h) but low bioavailability (12.59%).

Aim: An assay to detect anti-tocilizumab antibodies in the presence of high levels of circulating target and drug is needed for immunogenicity assessment in comparative clinical studies.Methods: An assay was developed and validated using a combination of blocking agents and dilutions to overcome target interference challenges.Results: No false-positive signal was detected in serum samples spiked with 350-500 ng/ml of IL-6 receptor. As low as 50 ng/ml of positive control antibodies could be detected in the presence of either 500 ng/ml of IL-6 or 250 μg/ml of the drug product. Assay also demonstrated high sensitivity, selectivity and precision.Conclusion: A robust, easy to perform immunogenicity assay was developed and validated for detecting anti-tocilizumab antibodies.

Min Meng received her PhD in biomedicinal chemistry from the School of Pharmacy, University of Maryland, in 1996. From 1996 to 1998, Meng was a postdoctoral fellow at the American Health Foundation, focusing on the carcinogenic toxicity of tobacco smoke using various chromatographic technologies such as LC-UV, GC-MS/MS and LC-MS/MS. From 1998 to 2017, Meng worked for Tandem Labs/LabCorp/Covance, a bioanalytical contract research organization (CRO), holding various positions from scientist to lab director and technical director. In 2017, Meng moved back to her hometown and set up a bioanalytical CRO, Denali Medpharma, Chongqing, China. In October 2023, Denali was acquired by Resolian Bioanalytics, a global bioanalytical CRO. Currently, Dr Meng is the chief scientific officer and president of the Asia Pacific region for Resolian Bioanalytics.

Background: The measurement of meropenem plasma concentrations is employed for dosing regimen individualization. The aim of this study was to develop and validate a LC-MS/MS assay for quantification of meropenem in capillary plasma microsamples. Methods: Samples were prepared by protein precipitation with acetonitrile, followed by clean-up with dichloromethane. The method was validated and applied to 12 paired samples of venous and capillary plasma. Results: The method was linear in the range of 0.5-50 μg/ml. Matrix effects were minimal. Inter- and intra-assay were 3.8-7.9% and 2.7-5.5%, respectively, while accuracy was 91.7-100.6%. Concentrations in capillary and venous plasma were highly correlated. Conclusion: An assay for the quantification of meropenem in capillary plasma microsamples was fully validated, showing potential for clinical application.

Aim: To assess the impact of experimental conditions on free serum concentrations as determined by ultrafiltration and HPLC-DAD analysis in a wide range of antibiotics.Materials & methods: Relative centrifugation force (RCF), temperature, pH and buffer were varied and the results compared with the standard protocol (phosphate buffer pH 7.4, 37°C, 1000 × g).Results: Generally, at 10,000 × g the unbound fraction (f_u) decreased with increasing molecular weight, and was lower at 22°C. In unbuffered serum, the f_u of flucloxacillin or valproic acid was increased, that of basic or amphoteric drugs considerably decreased. Comparable results were obtained using phosphate or HEPES buffer except for drugs which form metal chelate complexes.Conclusion: Maintaining a physiological pH is more important than strictly maintaining body temperature.

Aim: Validate a method to quantify 1-(5-fluoropentyl)-N-(2-phenylpropan-2-yl)-1H-indole-3-carboxamide (5F-CUMYL-PICA) and methyl 2-[[1-(5-fluoropentyl) indole-3-carbonyl] amino]-3,3-dimethyl-butanoate (5F-MDMB-PICA) in blood samples using GC-MS/MS. Materials & methods: A solid-phase extraction (SPE) method has been developed to quantify 5F-MDMB-PICA and 5F-CUMYL-PICA in authentic human blood samples. Results & conclusion: The limit of detection (LOD) was 0.1 and 0.11 ng/ml for 5F-CUMYL-PICA and 5F-MDMB-PICA, respectively, while the limit of quantification (LOQ) was 0.50 ng/ml for both two compounds. Recovery was 91.40, 82.54 and 85.10% for SPE, supported liquid extraction (SLE) and ISOLUTE C18; matrix effects 15, 24 and 22.5% for SPE, SLE and ISOLUTE C18; accuracy was 2.4-5.5 and 3.9-7.3% for SPE, SLE and ISOLUTE C18, while precision was 4.6-7.7 and 6.4-8.3% for SPE, SLE and ISOLUTE C18, respectively. The concentrations of 5F-CUMYL-PICA and 5F-MDMB-PICA in the authentic human blood samples were 2.18 and 3.07 ng/ml, respectively. The validated method was successfully used in supporting the quantification of analytes in blood.