Lindner W, Rath M, Stoschitzky K, Uray G
Institute of Pharmaceutical Chemistry, Karl-Franzens University of Graz, Austria.
J Chromatogr. 1989 Feb 24;487(2):375-83. doi: 10.1016/s0378-4347(00)83045-5.
A sensitive high-performance liquid chromatographic method was developed for the stereoselective assay of (R)- and (S)-propranolol in human plasma. The method involves diethyl ether extraction of the drugs and a racemic internal standard, N-tert.-butylpropranolol, followed by derivatization of the compounds with the chiral reagent (R,R)-O,O-diacetyl tartaric acid anhydride. The resulting diastereomeric derivatives were separated isocratically on a reversed-phase column. Quantitation was achieved by the peak-height ratio method with reference to the internal standard. The assay was accurate and reproducible in the concentration range 1-100 ng of (R)- and (S)-propranolol per ml plasma, using fluorescence detection at lambda ex 290 nm and lambda em 335 nm. The applicability of this method was demonstrated for the determination of concentration-time profiles of propranolol enantiomers in the course of comparative pharmacokinetic studies.
建立了一种灵敏的高效液相色谱法，用于人血浆中（R）-和（S）-普萘洛尔的立体选择性测定。该方法包括用乙醚萃取药物和外消旋内标N-叔丁基普萘洛尔，然后用手性试剂（R，R）-O，O-二乙酰酒石酸酐对化合物进行衍生化。所得非对映体衍生物在反相柱上进行等度分离。通过以内标为参照的峰高比法进行定量。使用激发波长为290nm、发射波长为335nm的荧光检测，该测定法在每毫升血浆中（R）-和（S）-普萘洛尔浓度为1-100ng的范围内准确且可重复。该方法的适用性在比较药代动力学研究过程中普萘洛尔对映体浓度-时间曲线的测定中得到了验证。
