Determination of metoclopramide in human plasma by LC-ESI-MS and its application to bioequivalance studies.
An LC-MS method for the determination of metoclopramide in human plasma was developed and validated. Sample preparation involved extraction with ethyl acetate. Chromatographic separation was performed on a Thermo Hypersil-Hypurity C18 (150 mm x 2.1 mm, 5 microm) with the mobile phase consisting of 40 mM ammonium acetate-methanol-acetonitrile. A single-quadrupole mass spectrometer with an electrospray interface was operated in the selected-ion monitoring mode to detect the [M+H]+ ions at m/z 300 for metoclopramide and at m/z 384 for the internal standard (prazosin). The method was validated over 0.78-50.00 ng mL(-1) for metoclopramide. The recovery was 67.8-83.1%, and the limit of quantitation (LOQ) detection was 0.78 ng mL(-1) for metoclopramide. The intra- and inter-day precision of the method at three concentrations was 5.0-13.6% with accuracy of 99.2-104.0%. Stability of compounds was established in a battery of stability studies. The method was successfully applied to bioequivalence studies of metoclopramide hydrochloride tablets to obtain the pharmacokinetic parameters.
Yan
Miao
M
Clinical Pharmacy and Pharmacology Research Institute, The Second Xiangya Hospital, Central South University, 139# Middle Renmin Road, Changsha, Hunan Province 410011, China.
Li
Huan-De
HD
Chen
Ben-Mei
BM
Liu
Xiao-Lei
XL
Zhu
Yun-Gui
YG
D000284:Administration, Oral; D044466:Asian People; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D016014:Linear Models; D008297:Male; D008787:Metoclopramide / Q000097:blood* / Q000493:pharmacokinetics* / Q000494:pharmacology; D011224:Prazosin / Q000097:blood; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013810:Therapeutic Equivalency
D008787:Metoclopramide; D011224:Prazosin