Le Corre P, Gibassier D, Sado P, Le Verge R
Laboratoire de Pharmacie Galénique et Biopharmacie, Université de Rennes I, France.
J Chromatogr. 1988 Oct 21;450(2):211-6. doi: 10.1016/s0021-9673(01)83908-x.
A method for the simultaneous determination of disopyramide and mono-N-desisopropyldisopyramide enantiomers extracted from human plasma and urine is presented. Separation and quantitation were carried out using two columns coupled in series, and UV detection at 254 nm. First, the racemates of the two compounds were separated using a reversed-phase column, and then the enantiomers were separated using a stereoselective column packed with human alpha 1-acid glycoprotein. The mobile phase was 8 mM phosphate buffer, pH 6.20-2-propanol (92:8, v/v). The coefficients of variation (%) for the plasma daily determination were 6.7% for R(-)- and S(+)-disopyramide at drug levels of 1.5 micrograms/ml, and 8.5% and 7.7% for R(-)- and S(+)-mono-N-desisopropyldisopyramide, respectively, at drug levels of 0.375 micrograms/ml. The method has allowed the study of stereoselective metabolism and pharmacokinetics of disopyramide after oral administration as a racemate.
本文介绍了一种同时测定从人血浆和尿液中提取的丙吡胺及其单-N-去异丙基丙吡胺对映体的方法。采用两根串联柱进行分离和定量，并在254nm处进行紫外检测。首先，使用反相柱分离两种化合物的外消旋体，然后使用填充有人α1-酸性糖蛋白的立体选择性柱分离对映体。流动相为8mM磷酸盐缓冲液，pH6.20-异丙醇（92:8，v/v）。血浆每日测定的变异系数（%）在药物浓度为1.5μg/ml时，R(-)-和S(+)-丙吡胺分别为6.7%；在药物浓度为0.375μg/ml时，R(-)-和S(+)-单-N-去异丙基丙吡胺分别为8.5%和7.7%。该方法有助于研究口服外消旋体丙吡胺后的立体选择性代谢和药代动力学。
