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J Pharm Sci. 1989 Jul;78(7):592-7.

High-performance liquid chromatographic assay of diltiazem and six of its metabolites in plasma: application to a pharmacokinetic study in healthy volunteers.

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1
College of Pharmacy, Department of Medicine, Dalhousie University, Nova Scotia, Canada.

Abstract

A sensitive and specific reversed-phase high-performance liquid chromatographic assay for simultaneous determination of plasma concentrations of diltiazem and six of its metabolites known to occur in humans is reported. Using 2 mL of plasma, the lower limit of quantitation of the assay was less than 10 ng/mL of diltiazem and each of the metabolites, with coefficients of variation of less than 10%. The assay was successfully applied to determine the kinetics of diltiazem and its major metabolites in four healthy volunteers after each received a single 90-mg oral dose of diltiazem. In addition to the previously reported two major metabolites in humans, deacetyl diltiazem (M1) and N-monodemethyl diltiazem (MA), another previously unreported major metabolite, deacetyl N-monodemethyl diltiazem (M2), was present at comparable concentrations to M1 and MA in all four volunteers. In addition, another metabolite, deacetyl diltiazem N-oxide (M1-NO), which was previously found most abundant in urine, was also estimated in the plasma of two volunteers. Two other known human metabolites, deacetyl O-demethyl diltiazem (M4) and deacetyl N,O-didimethyl diltiazem (M6), were not detected in any of the four study subjects. The average maximum plasma concentrations of M1, M2, MA, and M1-NO were 10, 15, 26, and 13%, respectively, of the mean maximum diltiazem concentrations.

PMID:
2778663
[Indexed for MEDLINE]

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