High performance liquid chromatography-tandem mass spectrometric determination of rupatadine in human plasma and its pharmacokinetics.
A simple, rapid, sensitive and selective liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the quantification of rupatadine in human plasma using estazolam as internal standard (IS). Following liquid-liquid extraction, the analytes were separated using a mobile phase of methanol-ammonium acetate (pH 2.2; 5mM) (50:50, v/v) on a reverse phase C18 column and analyzed by a triple-quadrupole mass spectrometer in the positive ion and multiple reaction monitoring (MRM) mode, m/z 416-->309 for rupatadine and m/z 295-->267 for the IS. The assay exhibited a linear dynamic range of 0.1-100 ng/ml for rupatadine in human plasma. The lower limit of quantification (LLOQ) was 0.1 ng/ml with a relative standard deviation of less than 20%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. The validated LC-MS/MS method has been successfully applied to study the pharmacokinetics of rupatadine in healthy volunteers.
Tian
Yuan
Y
Key laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing 210009, China.
Zhang
Jingjing
J
Lin
Hui
H
Liang
Jiabi
J
Zhang
Zunjian
Z
Chen
Yun
Y
D000328:Adult; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D018592:Cross-Over Studies; D003533:Cyproheptadine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D004949:Estazolam / Q000737:chemistry; D005260:Female; D005615:Freezing; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D015394:Molecular Structure; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012737:Sex Factors; D013607:Tablets / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors
D013607:Tablets; C103639:rupatadine; D003533:Cyproheptadine; D004949:Estazolam