title: A high performance liquid chromatography-tandem mass spectrometric method for the determination of mefenamic acid in human plasma: application to pharmacokinetic study.
abstract: In the present study, the development and validation of an LC-MS/MS method for quantifying mefenamic acid in human plasma is described. The method involves liquid-liquid extraction using diclofenac as an internal standard (IS). Chromatographic separation was achieved on a Thermo Hypurity C(18) , 50 × 4.6 mm, 5 µm column with a mobile phase consisting of 2 m m ammonium acetate buffer and methanol (pH 4.5 adjusted with glacial acetic acid; 15:85, v/v) at a flow-rate of 0.75 mL/min and the total run time was 1.75 min. Analyte was introduced to the LC-MS/MS using an atmospheric pressure ionization source. Both the drug and IS were detected in negative-ion mode using multiple reaction monitoring m/z 240.0 → 196.3 and m/z 294.0 → 250.2, respectively, with a dwell time of 200 ms for each of the transitions. The standard curve was linear from 20 to 6000 ng/mL. This assay allows quantification of mefenamic acid at a concentration as low as 20 ng/mL in human plasma. The observed mean recovery was 73% for the drug. The applicability of this method for pharmacokinetic studies has been established after successful application during a 12-subject bioavailabity study.
authors.affiliation: Department of Pharmaceutical Chemistry, Bharati Vidyapeeth University, Poona College of Pharmacy, Pune, Maharashtra, India.
authors.forename: Mahadeo
authors.initials: M
authors.lastname: Mahadik
authors.forename: Sunil
authors.initials: S
authors.lastname: Dhaneshwar
authors.forename: Ravindra
authors.initials: R
authors.lastname: Bhavsar
mesh_terms: D000085:Acetates; D000925:Anticoagulants / Q000494:pharmacology; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004008:Diclofenac; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016014:Linear Models; D059625:Liquid-Liquid Extraction; D008297:Male; D008528:Mefenamic Acid / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D000432:Methanol; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000085:Acetates; D000925:Anticoagulants; D004008:Diclofenac; D008528:Mefenamic Acid; C018824:ammonium acetate; D000432:Methanol