Development and Validation of a Bioanalytical Method for the Simultaneous Determination of 14 Antiretroviral Drugs using Liquid Chromatography-Tandem Mass Spectrometry

• Main Authors: Alper Daskapan, Kai van Hateren, Ymkje Stienstra, Jos Kosterink, Tjip van der Werf, Daan Touw, Jan-Willem Alffenaar
• Format: Article
• Language: English
• Published: Betasciencepress Publishers 2018-04-01
• Series: Journal of Applied Bioanalysis
• Subjects: lc-ms/ms; antiretrovirals; hiv; TDM
• Online Access: https://doi.org/10.17145/jab.18.007
• ISSN: 2405-710X

OBJECTIVES: The aim was to develop and validate a LC-MS/MS assay to determine antiretrovirals in human plasma for routine therapeutic drug monitoring. METHODS: The selectivity, sensitivity, linearity, accuracy, precision, recovery, matrix effect, stability and dilution integrity and carry-over were validated according to EMA and FDA standards. RESULTS: For accuracy and precision, the highest overall bias was 11.3% at LLOQ of both lopinavir and saquinavir. The highest overall CV was 15.6% at the LLOQ of darunavir. Storage stability at 4°C, 20–25°C and 10°C had a maximum CV of 13.2% at low QC level (0.2 mg/L) for saquinavir. Freeze-thaw stability had a maximum overall bias of 7.4% at low QC level (0.8 mg/L) for tipranavir. Selectivity and specificity showed no interfering peaks of more than 20% of the LLOQ. CONCLUSIONS: The bioanalytical method is suitable for both TDM in standard care and clinical studies.