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Simultaneous determination of disopyramide and its mono-N-dealkylated metabolite enantiomers in human plasma and urine by enantioselective high-performance liquid chromatography.

Authors
  • Takahashi, H
  • Tamura, A
  • Ogata, H
  • Masuhara, K
Type
Published Article
Journal
Journal of chromatography
Publication Date
Aug 03, 1990
Volume
529
Issue
2
Pages
347–358
Identifiers
PMID: 2229254
Source
Medline
License
Unknown

Abstract

Enantiomers of disopyramide (DP) and its mono-N-dealkylated metabolite (MND) were determined in human plasma and urine by enantioselective high-performance liquid chromatography using a chiral stationary-phase column. This method was precise and sensitive: the mean recoveries from plasma at a concentration of 0.5 microgram/ml were 101.1% for (+)-DP, 98.0% for (-)-DP, 94.4% for (+)-MND and 82.9% for (-)-MND; the within- and between-day coefficients of variation at the same concentration were 4.4 and 3.3% for (+)-DP, 4.7 and 4.1% for (-)-DP, 6.5 and 4.1% for (+)-MND and 7.8 and 2.4% for (-)-MND for plasma; the lower detection limits were 40 ng/ml for (+)-DP, 80 ng/ml for (-)-DP, 100 ng/ml for (-)-MND and 200 ng/ml for (+)-MND, for 0.5 ml of plasma and 0.2 ml of urine. The ultrafiltration technique was used for determination of the unbound concentration of DP enantiomers in plasma. A preliminary study of the determination of DP and MND enantiomers in plasma and urine samples from a healthy subject given racemic DP demonstrated the clinical applicability of the present method for therapeutic monitoring and pharmacokinetic studies.

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