Simultaneous determination of rupatadine and its metabolite desloratadine in human plasma by a sensitive LC-MS/MS method: application to the pharmacokinetic study in healthy Chinese volunteers.
A sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed for simultaneous determination of rupatadine and its metabolite desloratadine in human plasma. After the addition of diphenhydramine, the internal standard (IS), plasma samples were extracted with a mixture of methyl tert-butyl ether and n-hexane (1:1, v/v). The analysis was performed on a Ultimate AQ-C18 (4.6mm x 100mm, 5microm) column using a mobile phase consisting of a 80/20 mixture of methanol/water containing 0.0005% formic acid pumped at 0.3mlmin(-1). The analytes and the IS were detected in positive ionization mode and monitoring their precursor-->product ion combinations of m/z 416-->309, 311-->259, and 256-->167, respectively, in multiple reaction monitoring mode. The linear ranges of the assay were 0.1-50 and 0.1-20ngml(-1) for rupatadine and desloratadine, respectively. The lower limits of reliable quantification for both rupatadine and desloratadine were 0.1ngml(-1), which offered high sensitivity and selectivity. The within- and between-run precision was less than 7.2%. The accuracy ranged from -9.2% to +6.4% and -7.2% to +7.2% for rupatadine and desloratadine in quality control samples at three levels, respectively. The method has been successfully applied to a pharmacokinetic study of rupatadine and its major metabolite after oral administration of 10, 20 and 40mg rupatadine tablets to healthy Chinese volunteers.
Wen
Jun
J
Department of Pharmaceutical Analysis, Second Military Medical University, Shanghai 200433, People's Republic of China.
Hong
Zhanying
Z
Wu
Yiwen
Y
Wei
Hua
H
Fan
Guorong
G
Wu
Yutian
Y
D000328:Adult; D044466:Asian People; D002138:Calibration; D002853:Chromatography, Liquid / Q000295:instrumentation / Q000379:methods; D003533:Cyproheptadine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D005260:Female; D005561:Formates / Q000737:chemistry; D005615:Freezing; D039563:Histamine H1 Antagonists, Non-Sedating / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D017336:Loratadine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D000432:Methanol / Q000737:chemistry; D015394:Molecular Structure; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013607:Tablets; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors; D014867:Water / Q000737:chemistry; D055815:Young Adult
D005561:Formates; D039563:Histamine H1 Antagonists, Non-Sedating; D010972:Platelet Activating Factor; D013607:Tablets; D014867:Water; C030544:formic acid; C103639:rupatadine; D003533:Cyproheptadine; D017336:Loratadine; C121345:desloratadine; D000432:Methanol