title: Quantitative determination of microbicidal spermicide 'nonoxynol-9' in rabbit plasma and vaginal fluid using LC-ESI-MS/MS: application to pharmacokinetic study.
abstract: 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.
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR - Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, Rafi Marg, New Delhi 110001, India.
authors.forename: Yashpal S
authors.initials: YS
authors.lastname: Chhonker
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR - Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, Rafi Marg, New Delhi 110001, India.
authors.forename: Hardik
authors.initials: H
authors.lastname: Chandasana
authors.affiliation: Medicinal & Process Chemistry Division, CSIR - Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, Rafi Marg, New Delhi 110001, India.
authors.forename: Veenu
authors.initials: V
authors.lastname: Bala
authors.affiliation: Endocrinology Division, CSIR - Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Lokesh
authors.initials: L
authors.lastname: Kumar
authors.affiliation: Medicinal & Process Chemistry Division, CSIR - Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Vishnu Lal
authors.initials: VL
authors.lastname: Sharma
authors.affiliation: Endocrinology Division, CSIR - Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Gopal
authors.initials: G
authors.lastname: Gupta
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR - Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, Rafi Marg, New Delhi 110001, India. Electronic address: rabi.cdri@gmail.com.
authors.forename: Rabi S
authors.initials: RS
authors.lastname: Bhatta
mesh_terms: D000818:Animals; D001826:Body Fluids / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005260:Female; D057230:Limit of Detection; D016014:Linear Models; D017137:Nonoxynol / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics*; D011817:Rabbits; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014621:Vagina / Q000378:metabolism
chemical_list: D017137:Nonoxynol
keywords: LC–MS/MS; Microbicide; Nonoxynol-9; Pharmacokinetics; Spermicide