PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Bioanalysis of the Geneva Phenotyping Cocktail in Whole Blood Collected with Volumetric Absorptive Microsampling by LC-MS/MS for Application in a South African Cohort
Version 1
: Received: 11 June 2024 / Approved: 11 June 2024 / Online: 11 June 2024 (18:26:02 CEST)
How to cite:
Leuschner, M.; Cromarty, A. D.; Sheva, K. Bioanalysis of the Geneva Phenotyping Cocktail in Whole Blood Collected with Volumetric Absorptive Microsampling by LC-MS/MS for Application in a South African Cohort. Preprints2024, 2024060728. https://doi.org/10.20944/preprints202406.0728.v1
Leuschner, M.; Cromarty, A. D.; Sheva, K. Bioanalysis of the Geneva Phenotyping Cocktail in Whole Blood Collected with Volumetric Absorptive Microsampling by LC-MS/MS for Application in a South African Cohort. Preprints 2024, 2024060728. https://doi.org/10.20944/preprints202406.0728.v1
Leuschner, M.; Cromarty, A. D.; Sheva, K. Bioanalysis of the Geneva Phenotyping Cocktail in Whole Blood Collected with Volumetric Absorptive Microsampling by LC-MS/MS for Application in a South African Cohort. Preprints2024, 2024060728. https://doi.org/10.20944/preprints202406.0728.v1
APA Style
Leuschner, M., Cromarty, A. D., & Sheva, K. (2024). Bioanalysis of the Geneva Phenotyping Cocktail in Whole Blood Collected with Volumetric Absorptive Microsampling by LC-MS/MS for Application in a South African Cohort. Preprints. https://doi.org/10.20944/preprints202406.0728.v1
Chicago/Turabian Style
Leuschner, M., Allan Duncan Cromarty and Kim Sheva. 2024 "Bioanalysis of the Geneva Phenotyping Cocktail in Whole Blood Collected with Volumetric Absorptive Microsampling by LC-MS/MS for Application in a South African Cohort" Preprints. https://doi.org/10.20944/preprints202406.0728.v1
Abstract
Poor therapeutic outcomes have been attributed to inter-individual and interethnic variability in cytochrome P450 (CYP450)-dependent metabolism and altered drug retention associated with P-glycoprotein (P-gp). An individualized pharmacotherapeutic approach would benefit the genetically diverse South African population. The study aim was to develop a validated, targeted, analytical method to quantify seven probe drugs and their metabolites in dried blood spots (DBS) using the Mitra™ volumetric absorptive micro-sampling device for blood collection. An Agilent liquid chromatography (LC) system coupled to a Sciex 4000 QTRAP tandem mass spectrometer (MS) was used for method optimization and validation. Targeted LC-MS/MS methods were validated according to ICH guidelines. The validated LC-MS/MS method met the required bioanalytical standards for specificity, sensitivity, linearity, accuracy, precision, carry-over, and stability. This study successfully validated the use of DBS, collected with the Mitra™ microsampling device, to measure expected probe drug and metabolite concentrations using the “Geneva phenotyping cocktail” for the purpose of simultaneous phenotyping of in vivo CYP450 metabolic activity of the CYP1A2, -2B6, -2C9, -2C19, -2D6, and -3A4 enzymes, and P-gp transport activity. However, statistical analysis using Bland-Altman plots showed that not all analytes exhibited linear distribution pharmacokinetics between DBS and plasma, which influenced the predicted vs real plasma concentrations based on measurements in a DBS matrix. These findings were attributed to the blood-to-plasma concentration ratio, the physicochemical properties and stability of the analytes, and the extraction efficiency of the Mitra™ sampler. More research is required before DBS sampling can be substituted for conventional plasma sampling
Medicine and Pharmacology, Endocrinology and Metabolism
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
