High-performance liquid chromatographic determination of the conjugate metabolites of moxisylyte in human plasma and urine.
Sensitive and specific high-performance liquid chromatographic methods with fluorescence detection are described for the determination of the metabolites of moxisylyte (4-(2-dimethylaminoethoxy)-5-isopropyl-2-methylphenyl acetate) in human plasma and urine. Deacetylmoxisylyte glucuroconjugate (DAM-G) was hydrolysed enzymatically using 1-glucuronidase and quantified as the difference between the DAM concentrations determined after and before hydrolysis. The two sulphate derivatives (deacetylmoxisylyte sulphoconjugate, DAM-S and monomethyldeacetylmoxisylyte sulphoconjugate, MDAM-S), were analysed without prior hydrolysis. Their extraction from plasma and urine, as well as that of DAM from plasma, involved the use of C18 cartridges adapted on a Benchmate workstation. DAM in urine was quantified after liquid-liquid extraction. The two methods were validated for specificity, linearity, intra- and inter-day precision and accuracy. Precision was generally < or = 15% and accuracy < or = 12%. In plasma, the limits of quantification were 2.5 ng/ml for DAM and 2.8 ng/ml for the two sulphates, in urine, they were 40 ng/ml for DAM and 200 ng/ml for the sulphates. These methods were used for pharmacokinetic studies in healthy subjects.
Marquer
C
C
Laboratoires Debat, Garches, France.
Bressolle
F
F
D000317:Adrenergic alpha-Antagonists / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D013948:Moxisylyte / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014665:Vasodilator Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine*
D000317:Adrenergic alpha-Antagonists; D014665:Vasodilator Agents; D013948:Moxisylyte