Simultaneous determination of disopyramide and its mono-N-dealkylated metabolite enantiomers in human plasma and urine by enantioselective high-performance liquid chromatography.
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.
Takahashi
H
H
Department of Biopharmaceutics, Meiji College of Pharmacy, Tokyo, Japan.
Tamura
A
A
Ogata
H
H
Masuhara
K
K
D001798:Blood Proteins / Q000378:metabolism; D002317:Cardiovascular Agents / Q000032:analysis / Q000097:blood / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D004206:Disopyramide / Q000031:analogs & derivatives* / Q000032:analysis* / Q000097:blood / Q000652:urine; D006801:Humans; D011485:Protein Binding; D012997:Solvents; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D001798:Blood Proteins; D002317:Cardiovascular Agents; D012997:Solvents; D004206:Disopyramide