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

Abstract

OBJECTIVES: The aim was to develop and validate a LC-MS/MS assay to det. antiretrovirals in human plasma for routine therapeutic drug monitoring. METHODS: The selectivity, sensitivity, linearity, accuracy, precision, recovery, matrix effect, stability and diln. integrity and carry-over were validated according to EMA and FDA stds. 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 max. CV of 13.2% at low QC level (0.2 mg/L) for saquinavir. Freeze-thaw stability had a max. 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 bioanal. method is suitable for both TDM in std. care and clin. studies. [on SciFinder(R)]