Column-switching liquid chromatographic determination of ML-1035 sulphoxide and its sulphone and sulphide metabolites in rat urine.
A fully automated column-switching LC assay has been developed for the simultaneous determination of a gastroprokinetic agent, ML-1035 sulphoxide, and its sulphone and sulphide metabolites in rat urine. ML-1035 Sulphoxide is a metoclopramide analogue. The method involved direct injection of a diluted urine sample into a CN extraction column for sample clean-up. Polar urine components, including proteins, were flushed to waste. The retained compounds were then eluted onto a C8 analytical column for further separation and analysis by fluorescence detection. After the subsequent washing and re-equilibration with a sequence of three solvent mixtures, the extraction column was ready for the next injection. The recovery of the compounds from the extraction column was 85-90%. The limit of quantitation for all compounds of interest was 25 ng ml-1 or lower, using a 100 microliters specimen of urine. Good inter-day precision (2.1-10.0%), accuracy (0.3-18.0%), and linearity were obtained for all compounds over a range of 25-1000 ng ml-1. The applicability of the LC method was validated with urine samples from rats that had received ML-1035 sulphoxide.
Kuo
B S
BS
Drug Metabolism Section, Marion Merrell Dow Research Institute, Kansas City, MO 64134.
Poole
J C
JC
Mandagere
A
A
Hwang
K K
KK
D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D004355:Drug Stability; D008787:Metoclopramide / Q000031:analogs & derivatives* / Q000652:urine; D015394:Molecular Structure; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
C075796:metoclopramide sulfide; C075797:metoclopramide sulfone; C071737:ML 1035; D008787:Metoclopramide