Simultaneous determination of lamivudine, stavudine and nevirapine in human plasma by LC–MS/MS and its application to pharmacokinetic study in clinic

Abstract

A new high-throughput LC-MS/MS method for the simultaneous determination of lamivudine (3TC), stavudine (d4T) and nevirapine (NVP) in human plasma is presented, with zidovudine as an internal standard. The analytes were extracted from plasma by protein precipitation and only 150 microL plasma was needed. Chromatographic separation was achieved on a Shiseido C(8) column (150 x 2.0 mm, 5 microm) with a total run time of 6 min. A tandem mass spectrometric detection was conducted using multiple reaction monitoring under positive ionization mode with an electrospray ionization interface. The method was developed and validated over the concentration range of 25-5000 ng/mL for 3TC and NVP and 20-4000 ng/mL for d4T. The method was validated in terms of intra- and inter-day precision (< or = 8.6%), accuracy (within +/- 8.4%), linearity and specificity. The method has been successfully applied to the pharmacokinetic study of a combination treatment of 300 mg lamivudine, 30 mg stavudine and 200 mg nevirapine in 22 healthy male volunteers under fasting conditions.

Exploring dried blood spot sampling technique for simultaneous quantification of antiretrovirals: lamivudine, stavudine and nevirapine in a rodent pharmacokinetic study

“…To date, two specific LC‐MS/MS methods in human plasma for the simultaneous quantification of lamivudine, stavudine and nevirapine have been reported (Mistri et al ., ; Li et al ., ). Mistri et al .…”

Application of simple and sensitive LC‐MS/MS approach for trace level quantification of potential genotoxic impurities in lamivudine salicylate formulations

“…Several analytical methods were reported in literature for the estimation of LAM with other substances such as zidovudine, tenofovir, etc., in human plasma, serum and rat tissue, etc., by using sensitive GC‐MS and LC‐MS/MS . The determination of genotoxic alkyl methane sulfonates, alkyl para toluene sulfonates and some other impurities in LAM were also reported .…”

Liquid Chromatography-Tandem Mass Spectrometric Assay for Determination of Stavudine in Human Plasma

“…Determination of stavudine in plasma by high performance liquid chromatography method has been described [2,3]; analysis time was more than 12 minutes. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) method [4] was established for the simultaneous monitoring of multiple anti-HIV drugs in vivo plasma concentrations after long-term combination therapy of AIDS. The LC-MS/MS [5] method needs a larger workload because external standard was used.…”