Determination of manidipine and its pyridine metabolite in human serum by high-performance liquid chromatography with ultraviolet detection and column switching.
A highly sensitive and selective high-performance liquid chromatographic method using column switching is described for the determination of the dihydropyridine calcium antagonist manidipine (I),2-[4-(diphenylmethyl)-1-piperazinyl]ethyl methyl (+/- )-1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5- pyridinedicarboxylate, and its pyridine metabolite (II), 2-[4-(diphenylmethyl)-1-piperazinyl]ethyl methyl 2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridinedicarboxylate, in human serum. The method is based on the combination of the column-switching technique and ion-pair chromatography. In the first ODS column, I and II are preseparated from endogenous substances in serum with a mobile phase containing sodium nonane sulphonate as an ion-pair reagent. After column switching, in the second ODS column, the heart-cut fraction containing I and II is further separated from the co-eluted substances through the first column with a mobile phase containing no ion-pair reagent. By using microbore columns with a diameter of 2.1 mm, the sensitivity is almost double that given by conventional bore columns with a diameter of 4.6 mm. The method offers high sensitivity and selectivity with short-wavelength ultraviolet detection at 230 nm. The detection limits of both I and II are 0.1 ng/ml using 1 ml of serum. The method is suitable for the pharmacokinetic study of I.2HCl after oral administration to man.
Miyabayashi
T
T
Analytical Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Yamashita
K
K
Aoki
I
I
Motohashi
M
M
Yashiki
T
T
Yatani
K
K
D000284:Administration, Oral; D002121:Calcium Channel Blockers / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D004095:Dihydropyridines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D009578:Nitrobenzenes; D010879:Piperazines; D011725:Pyridines / Q000097:blood*; D013056:Spectrophotometry, Ultraviolet
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009578:Nitrobenzenes; D010879:Piperazines; D011725:Pyridines; C061857:2-(4-(diphenylmethyl)-1-piperazinyl)ethylmethyl-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate; C054218:manidipine