Validation of a reversed-phase HPLC method for directly quantifying the enantiomers of MDL 74,156, the primary metabolite of dolasetron mesylate, in human plasma.
A direct chiral HPLC method has been developed and validated to quantitate the enantiomers of MDL 74156, the primary metabolite of dolasetron mesylate, in human plasma over the concentration range 1.70-340 ng ml-1. Dolasetron mesylate is a 5-HT3 receptor antagonist that is currently being developed as an antiemetic. Both enantiomers of MDL 74154 and the internal standard (granisetron) were first extracted from alkanized plasma using methyl t-butyl ether. The analytes were then back-extracted into formic acid, separated on a ovomucoid-bonded HPLC column, and detected by native fluorescence (excitation wavelength of 274 nm and emission wavelength of 345 nm). The complete validation demonstrated the method to be accurate, precise, and specific for the direct quantitation of MDL 74156 enantiomers in human plasma. This procedure has been used on a routine basis to quantify the relative concentrations of each enantiomer of MDL 74 156 in both oral and intravenous pharmacokinetic studies of dolasetron mesylate in normal human volunteers.
McElvain
J S
JS
Department of Bioanalytics, Hoechst Marion Roussel Inc., Kansas City, MO 64131, USA.
Vandiver
V J
VJ
Eichemeier
L S
LS
D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006801:Humans; D007211:Indoles / Q000097:blood* / Q000378:metabolism; D011807:Quinolizines / Q000097:blood* / Q000378:metabolism; D012015:Reference Standards; D012702:Serotonin Antagonists / Q000097:blood*; D013237:Stereoisomerism
D007211:Indoles; D011807:Quinolizines; D012702:Serotonin Antagonists; C060344:dolasetron; C110718:hydrodolasetron