Quantitative determination of microbicidal spermicide 'nonoxynol-9' in rabbit plasma and vaginal fluid using LC-ESI-MS/MS: Application to pharmacokinetic study

Nonoxynol-9 (N-9), a microbicidal spermicide, has been in use as an over-the-counter contraceptive since the 1960s. A detailed account of its pharmacokinetic profile using highly sensitive detection method has not been reported yet. We developed and validated a rapid, selective and sensitive high-performance liquid chromatography coupled with tandem mass spectrometry (LC MS/MS) method for N-9 detection in plasma and simulated vaginal fluid. The analytes were quantified using reverse phase Thermo Accucore C-18 (150 mm x 4.6 mm, 5 mu m) column with isocratic elution using acetonitrile: 0.1% formic acid in triple distilled water (90:10, v/v) as mobile phase. The ionization was optimized using ESI (+) and selectivity was achieved by tandem mass spectrometric analysis using MRM transition, m/z 617.4 -> 133.2 for N-9 and m/z 180.1 -> 138.1 for phenacetin. The method was linear over the range 0.195-100 ng/mL. The method was accurate and precise with intra-batch and inter-batch accuracy (% bias) of less than +/- 15% and precision (% CV) of <15% for N-9. The mean peak plasma concentration (C-max) 4.87 +/- 0.37 ng/mL was achieved 1.0 h after vaginal application with terminal half-life 1.45 +/- 0.07 h in rabbits. The validated method was successfully applied for pharmacokinetic study of N-9 in rabbits after vaginal administration. (C) 2014 Elsevier B.V. All rights reserved.