Kanazawa H, Konishi Y, Matsushima Y, Takahashi T
Kyoritsu College of Pharmacy, Tokyo, Japan.
J Chromatogr A. 1998 Feb 27;797(1-2):227-36. doi: 10.1016/s0021-9673(97)00928-x.
Though liquid chromatography-mass spectrometry (LC-MS) is a powerful tool for analysis of drugs and their metabolites, it does not allow the use of a non-volatile buffer such as phosphate buffer. We used a column-switching desalting system in combination with atmospheric pressure chemical ionization LC-MS for analysis of sedatives and anaesthetics. The drugs examined were flumazenil, butorphanol, midazolam, lorazepam, phenobarbital and flunitrazepam. The separation was carried out on a reversed-phase column using acetonitrile-0.1 M phosphate buffer as a mobile phase. The mass spectra are almost the same as those obtained by direct analysis and the molecular ions were clearly observed. In the analysis, phosphate buffer was completely removed with the trapping column and did not interfere with ionization of the drugs in MS. The chiral separation of lorazepam was achieved on a chiral column with UV, optical rotatory detection and MS. This method is sufficiently sensitive and accurate for the pharmacokinetic studies of these drugs in biological samples.
尽管液相色谱-质谱联用(LC-MS)是分析药物及其代谢物的强大工具,但它不能使用诸如磷酸盐缓冲液之类的非挥发性缓冲液。我们将柱切换脱盐系统与大气压化学电离LC-MS联用,用于分析镇静剂和麻醉剂。所检测的药物有氟马西尼、布托啡诺、咪达唑仑、劳拉西泮、苯巴比妥和氟硝西泮。在反相柱上以乙腈-0.1M磷酸盐缓冲液作为流动相进行分离。质谱图与直接分析获得的质谱图几乎相同,并且能清晰观察到分子离子。在分析过程中,磷酸盐缓冲液通过捕集柱被完全去除,且不会干扰药物在质谱中的电离。劳拉西泮在手性柱上通过紫外、旋光检测和质谱实现了手性分离。该方法对于这些药物在生物样品中的药代动力学研究具有足够的灵敏度和准确性。