Clark B J, Hamdi A, Berrisford R G, Sabanathan S, Mearns A J
Pharmaceutical Chemistry, School of Pharmacy, University of Bradford, U.K.
J Chromatogr. 1991 Aug 16;553(1-2):383-90. doi: 10.1016/s0021-9673(01)88508-3.
A previously unreported coupled achiral-chiral high-performance liquid chromatographic method has been developed to assay the levels of bupivacaine and its enantiomers in plasma samples, after the local anaesthetic had been given as a continuous extrapleural intercostal nerve block for 4 days, to relieve postoperative pain following thoracotomy. The method has been used to determine maximum, individual enantiomer and steady state levels in conjunction with an assessment of whether accumulation of bupivacaine occurs. An off-line extraction sample preparation is involved before determination of the "total" levels and final sample clean-up on a cyanopropyl silica column prior to "heart cutting" of the bupivacaine peak to a Chiral-AGP column for assay of the enantiomeric ratio. For an initial 5 patient number the mean maximum level was 5.43 micrograms/ml against a reported toxic level of around 5 micrograms/ml, which was reached in 72 h and the S-enantiomer gave slightly increased concentrations over the R-enantiomer for which there is some evidence of higher toxicity.
已开发出一种此前未报道的非手性-手性联用高效液相色谱法，用于测定血浆样本中布比卡因及其对映体的含量。该局部麻醉药以持续胸膜外肋间神经阻滞方式给药4天，用于缓解开胸术后疼痛。该方法已用于结合评估布比卡因是否发生蓄积来测定其最大、各对映体及稳态水平。在测定“总”含量之前需进行离线萃取样品制备，在将布比卡因峰“中心切割”至手性AGP柱以测定对映体比例之前，先在氰丙基硅胶柱上进行最终样品净化。对于最初的5例患者，平均最大水平为5.43微克/毫升，而报道的中毒水平约为5微克/毫升，该水平在72小时时达到，且S-对映体的浓度比R-对映体略有升高，有证据表明R-对映体毒性更高。
