title: Rapid quantitative analysis of ormeloxifene and its active metabolite, 7-desmethyl ormeloxifene, in rat plasma using liquid chromatography-tandem mass spectrometry.
abstract: Ormeloxifene (ORM) is a non-steroidal, selective estrogen receptor modulator used as a once a week oral contraceptive and is intended for long-term clinical use by females. Therefore, a simple, sensitive and rapid LC-MS/MS method was developed and validated for simultaneous quantification of ORM and its active metabolite (7-desmethyl ormeloxifene, 7-DMO) in rat plasma. Also, the method was partially validated in human plasma. Chromatographic separation was achieved on Discovery HS C-18 column (5μm, 50×4.6mm) with mobile phase [acetonitrile: aqueous ammonium acetate (0.01M) buffer (85: 15, %v/v)] at a flow rate of 0.8mL/min. The calibration curve was linear (r≥0.99) for a concentration range of 0.78-100ng/mL for both the analytes. The precision (%RSD; ORM, 1.3 to 13.4; 7-DMO, 3.1 to 15.0) and accuracy (%bias; ORM, -13.8 to 12.5; 7-DMO, -10.6 to 6.8) in both rat and human plasma were within the acceptable limits. The recovery for ORM and 7-DMO was always >79.1% and >72.9%, respectively. Both the analytes were found stable in rat plasma even after 30 days of storage at -80°C and on being subjected to three freeze-thaw cycles. The method has not only short run time (3.5min) but requires a low plasma sample volume (20μL) and is the first reported LC-MS/MS method for simultaneous quantification of the marketed drug known as centchroman (INN: ormeloxifene) and the metabolite 7-DMO in plasma. The method was applied to evaluate drug-drug interaction of ORM with the commonly prescribed antidepressant drug sertraline using serial sampling in rats.
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR - Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research, New Delhi, India.
authors.forename: Abhisheak
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR - Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research, New Delhi, India.
authors.forename: Swati
authors.initials: S
authors.lastname: Jaiswal
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR - Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research, New Delhi, India.
authors.forename: Mahendra
authors.initials: M
authors.lastname: Shukla
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Raebareli 229010, India.
authors.forename: Mohd Yaseen
authors.initials: MY
authors.lastname: Malik
authors.affiliation: Pharmacokinetics & Metabolism Division, CSIR - Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research, New Delhi, India. Electronic address: j_lal@cdri.res.in.
authors.forename: Jawahar
authors.initials: J
authors.lastname: Lal
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001578:Benzopyrans / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics* / Q000494:pharmacology; D002853:Chromatography, Liquid / Q000379:methods*; D003276:Contraceptives, Oral / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics* / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D005306:Fertilization / Q000187:drug effects; D006801:Humans; D016014:Linear Models; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D020280:Sertraline / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D001578:Benzopyrans; D003276:Contraceptives, Oral; C508548:ormeloxifene; D020280:Sertraline
keywords: Centchroman; Drug interaction; LC–MS/MS; Sertraline