Development, validation and clinical implementation of a UPLC-MS/MS bioanalytical method for simultaneous quantification of cabotegravir and rilpivirine E-isomer in human plasma.

Autor: Bevers LAH; Department of Pharmacy & Radboudumc Institute for Medical Innovation (RIMI), Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands. Electronic address: Lisanne.Bevers@radboudumc.nl., van Ewijk-Beneken Kolmer EWJ; Department of Pharmacy & Radboudumc Institute for Medical Innovation (RIMI), Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands., Te Brake HML; Department of Pharmacy & Radboudumc Institute for Medical Innovation (RIMI), Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands., Burger DM; Department of Pharmacy & Radboudumc Institute for Medical Innovation (RIMI), Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2024 Jan 20; Vol. 238, pp. 115832. Date of Electronic Publication: 2023 Nov 04.
DOI: 10.1016/j.jpba.2023.115832
Abstrakt: A reversed phase ultra-high performance liquid chromatography method was developed for the simultaneous quantification of cabotegravir (CAB) and the E-isomer of rilpivirine (RPV) in human EDTA plasma, also considering RPV E-isomer instability. Because of the instability of RPV (and CAB) in all light conditions, the (RPV Z-isomer/total RPV)-isomer ratio of RPV was determined for each stock, calibration curve standard, quality control sample and patient sample. [ 2 H 3 ]-CAB and [ 13 C 6 ]-RPV were used as internal standard. Sample preparation involved protein precipitation of plasma using methanol. An HSS T3 column with a guard column (set at 40 °C) was used for analyte separation. The mobile phase components were 65 % 0.1 % formic acid in water (A) and 35 % 0.1 % formic acid in acetonitrile (B) and the flow rate was 0.5 mL/min. Detection was performed with tandem mass spectrometry (MS/MS) in a total runtime of 3.0 min. The assay was validated over the concentration range of 0.0500 - 10.0 mg/L for CAB and 0.00300 - 3.00 mg/L for RPV. The average within-day and between-day accuracies for the assay in plasma were 101 % and 101 % for CAB and 97.6 % and 98.5 % voor RPV, respectively. Within-day and between-day precision in coefficients of variations (CV) were 5.0 %. Extraction recovery was 99 % and 102 % for CAB and its internal standard and 95 % and 97 % for RPV and its internal standard. As our aim was that the (Z-isomer RPV/total RPV) response ratio in patient samples had to be less than 10 % to give reliable results, the (Z-isomer RPV/total RPV) response ratio in stocks, calibration curve standards and internal quality control samples were also taken into account being maximal 0.9 % and 2.3 % respectively. This assay has been successfully used in our Therapeutic Drug Monitoring (TDM) service for people living with HIV on long-acting injectable therapy with CAB/RPV and will also be used in future pharmacokinetic studies.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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