Sensitive quantification of ranolazine in human plasma by liquid chromatography--tandem mass spectrometry with positive electrospray ionization.
A rapid, selective and sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method with positive electrospray ionization (ESI) was developed for the quantification of ranolazine in human plasma. After liquid-liquid extraction of ranolazine and internal standard (ISTD) phenoprolamine from a 100 microl specimen of plasma, HPLC separation was achieved on a Nova-Pak C(18) column, using acetonitrile-water-formic acid-10% n-butylamine (70:30:0.5:0.08, v/v/v/v) as the mobile phase. The mass spectrometer was operated in multiple reaction monitoring (MRM) mode using the transition m/z 428.5-->m/z 279.1 for ranolazine and m/z 344.3-->m/z 165.1 for the internal standard, respectively. Linear calibration curves were obtained in the concentration range of 5-4000 ng/ml, with a lower limit of quantitation (LLOQ) of 5 ng/ml. The intra- and inter-day precision values were below 3.7% and accuracy was within +/-3.2% at all three quality control (QC) levels. This method was found suitable for the analysis of plasma samples collected during the phase I pharmacokinetic studies of ranolazine performed in 28 healthy volunteers after single oral doses from 200 mg to 800 mg.
Tian
Lei
L
Clinical Pharmacology Center, Fu Wai Hospital, CAMS and PUMC, 167 Beilishi Road, Beijing 100037, PR China.
Jiang
Juanjuan
J
Huang
Yiling
Y
Hua
Lu
L
Liu
Hong
H
Li
Yishi
Y
D000083:Acetanilides / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D000284:Administration, Oral; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D010879:Piperazines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D000069458:Ranolazine; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D000083:Acetanilides; D004791:Enzyme Inhibitors; D010879:Piperazines; D000069458:Ranolazine