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 C18 (150 mm × 4.6mm, 5 μm) 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 (Cmax) 4.87 ± 0.37 ng/mL was achieved 1.0h 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.
['Chhonker|Yashpal S|YS|', 'Chandasana|Hardik|H|', 'Bala|Veenu|V|', 'Kumar|Lokesh|L|', 'Sharma|Vishnu Lal|VL|', 'Gupta|Gopal|G|', 'Bhatta|Rabi S|RS|']
D000818:Animals D001826:Body Fluids D002851:Chromatography, High Pressure Liquid D004355:Drug Stability D005260:Female D057230:Limit of Detection D016014:Linear Models D017137:Nonoxynol D011817:Rabbits D015203:Reproducibility of Results D053719:Tandem Mass Spectrometry D014621:Vagina
Microbicide Spermicide Nonoxynol-9 Pharmacokinetics LC–MS/MS