Simultaneous enantiomeric determination of a gastroprokinetic agent mosapride citrate and its metabolite in plasma using alpha 1-acid glycoprotein HPLC column.
Mosapride citrate, a novel benzamide-type gastroprokinetic agent, is clinically prescribed as a racemate and is metabolized to its des-4-fluorobenzyl structure (M-1). In order to analyze simultaneously the enantiomers of mosapride and M-1 in plasma, a simple and reproducible high-performance liquid chromatographic (HPLC) method has been developed. The enantiomeric separation and determination were successfully achieved using an alpha 1-acid glycoprotein column and gradient elution with a fluorimetric detection (excitation 314 nm/emission 352 nm). Both enantiomers of mosapride and M-1 were well separated between 20 and 22 min at pH 4.4 and between 4 and 7 min at pH 5.0, respectively. Accurate determinations are possible in the concentration ranges of 10-5000 ng ml-1 for mosapride enantiomers and 50-5000 ng ml-1 for M-1 enantiomers. The intra- and inter-day coefficients of variation are satisfactory for the pharmacokinetic study of mosapride.
Yokoyama
I
I
Department of Pharmacokinetics, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
Mizuki
Y
Y
Yamaguchi
T
T
Fujii
T
T
D000284:Administration, Oral; D000818:Animals; D001549:Benzamides / Q000097:blood*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005765:Gastrointestinal Agents / Q000097:blood*; D006863:Hydrogen-Ion Concentration; D008297:Male; D015394:Molecular Structure; D009025:Morpholines / Q000097:blood*; D009961:Orosomucoid; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013237:Stereoisomerism; D013997:Time Factors
D001549:Benzamides; D005765:Gastrointestinal Agents; D009025:Morpholines; D009961:Orosomucoid; C107818:4-amino-5-chloro-2-ethoxy-N-((2-morpholinyl)methyl)benzamide; C062720:mosapride