Quantification of trimetazidine in human plasma by liquid chromatography-electrospray ionization mass spectrometry and its application to a bioequivalence study.
A rapid, sensitive and specific liquid chromatography-electrospray ionization mass spectrometric (LC-ESI-MS) method has been developed for the quantification of trimetazidine in human plasma. The analyte and the internal standard (pseudoephedrine) were extracted from plasma samples with n-hexane-dichloromethane (1:1, v/v) and analyzed on a C18 column. The chromatographic separation was achieved within 3.5 min using the mobile phase consisting of methanol/0.05% formic acid (80:20, v/v) and the flow rate was 1.0 ml/min. Ion signals m/z 181.0 and 148.0 were measured in the positive mode for trimetazidine and pseudoephedrine, respectively. The calibration curves were linear within the range of 0.4 to approximately 120 ng/ml. The lower limit of quantification (LLOQ) was 0.4 ng/ml with 0.5 ml plasma sample. The intra- and inter-day precisions were lower than 12% in terms of relative standard deviation (RSD). The inter-day relative error (RE) as determined from quality control samples (QCs), ranged from -1.4% to 3.3%. This validated method was successfully applied to the bioequivalent evaluation of two brands of trimetazidine tablets in 20 healthy volunteers.
Wang
Z B
ZB
Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
Sun
J
J
Rong
R
R
Tang
J L
JL
He
Z G
ZG
D000328:Adult; D002138:Calibration; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D004809:Ephedrine / Q000097:blood; D006801:Humans; D007202:Indicators and Reagents; D008297:Male; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D013810:Therapeutic Equivalency; D014292:Trimetazidine / Q000097:blood* / Q000493:pharmacokinetics; D014665:Vasodilator Agents / Q000097:blood* / Q000493:pharmacokinetics
D007202:Indicators and Reagents; D014665:Vasodilator Agents; D004809:Ephedrine; D014292:Trimetazidine