title: Development and validation of a sensitive U-HPLC-MS/MS method with electrospray ionization for quantitation of ranolazine in human plasma: application to a clinical pharmacokinetic study.
abstract: A simple, sensitive and high-throughput ultra high-performance liquid chromatography electrospray ionization mass spectrometry (U-HPLC-ESI-MS/MS) method has been developed and validated for the determination of ranolazine in human plasma. Propafenone was employed as the internal standard (I.S.). The analytes were chromatographically separated on a BEH C(18) column (50 mm × 2.1 mm, 1.7 μm) with a mobile phase consisting of acetonitrile and aqueous ammonium acetate solution (0.06% formic acid, 7.5 mmol L(-1) ammonium acetate, 40:60, v/v). Detection of the analytes was achieved using positive ion electrospray ionization via multiple reactions monitoring mode. The mass transitions were m/z 428.3→279.3 for ranolazine and m/z 342.4→115.9 for propafenone. The assay was linear over the concentration range 1-3000 ng mL(-1), with correlation coefficients ≥0.997. The intra- and inter-day coefficients of variation were less than 8.9% in terms of relative standard deviation and accuracy ranged from 93.0 to 108.9% at all quality control levels. The validated method was a simple sample preparation procedure and short run-time (<2.0 min) method, which was successfully applied to a phase I pharmacokinetic study of ranolazine in Chinese healthy volunteers.
authors: The Clinical Pharmacy & Pharmacology Research Institute, The Second Xiangya Hospital, Central South University, Changsha 410011, People's Republic of China.
authors: Qin-You
authors: QY
authors: Tan
authors: Rong-Hua
authors: RH
authors: Zhu
authors: Huan-de
authors: HD
authors: Li
authors: Ping-Fei
authors: PF
authors: Fang
authors: Miao
authors: M
authors: Yan
authors: Qi-Zhi
authors: QZ
authors: Zhang
authors: Wen-Xing
authors: WX
authors: Peng
mesh_terms: D000083:Acetanilides / Q000097:blood* / Q000493:pharmacokinetics; D000328:Adult; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D010879:Piperazines / Q000097:blood* / Q000493:pharmacokinetics; D000069458:Ranolazine; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000083:Acetanilides; D010879:Piperazines; D000069458:Ranolazine