Application of high-performance liquid chromatography/laser spray mass spectrometry to legal medicine.

质谱仪(MS)是检测和识别药物和毒物的有用工具，近年来界面的发展使高效液相色谱(LC)与LC/MS或LC/MS/MS联用成为可能。电喷雾电离(ESI)被广泛用作LC/MS的电离方法，但需要更软、效率更高的电离方法。在本项目中，我们尝试将激光电离(LSI)这一新的软电离方法应用于法医毒物分析。在大规模集成电路中，目标化合物被红外激光光束电离。在这个项目中，最困难的问题之一是激光光束在毛细管尖端的适当调节；光路的延长和使用CCD摄像机对毛细管的监控，有助于调节毛细管尖端上的激光焦点。我们开发了一种灵敏而特异的方法来鉴定和定量人体体液和乌头块茎中的乌头生物碱，并将发表在《质谱学杂志》上。通过LSI，一些滥用药物，如可卡因、吗啡和苯丙胺的电离强度比传统的ESI高5~10倍。在阴性模式下，丙酸衍生物镇痛解热化合物的电离强度是ESI的20~30倍。所有化合物均采用直接输注方式。然而，离子强度很不稳定，因此很难对目标化合物进行在线分析，在未来的项目中，这种大规模的电离可以应用到纳米级的LC系统中，以获得更稳定的电离。

Mass spectrometry (MS) is a useful tool for detecting and identifying drugs and poisons ; recent progress of interfaces has enabled high-performance liquid chromatography (LC) to couple as LC/MS or LC/MS/MS. Electrospray ionization (ESI) is widely used as an ionization method for LC/MS, but softer ionization methods with higher efficiency are needed. In this project, we have tried to apply laser ionization (LSI), a new soft ionization method to forensic toxicological analyses. In LSI, target compounds are ionized by infrared laser beam.In this project, one of the most difficult problem is the appropriate adjustment of laser beam onto the tip of the capillary ; the elongation of light path and the monitoring of the capillary using a CCD camera, were useful for fee adjustment of the laser focus on the capillary tip.We used a time-of-flight (TOF) MS as a LC/MS system, and TOF-MS has higher mass resolution ; we have developed a sensitive and specific method for identifying and quantitating Aconitum alkaloids in human body fluids and Aconitum tubers, which will be published in the Journal of Mass Spectrometry.By LSI, some drugs-of-abuse, e.g.cocaine, morphines and amphetamines were ionized with 5 to 10 times higher intensities, compared to those by the conventional ESI. In the negative mode, propionic acid derivative analgesic-antipyretic compounds were ionized with 20 to 30 times higher intensities, compared to those by ESI. All those compounds were applied direct infusion mode. However, the ion intensities were quite unstable ; thus it seems difficult for the on-line analysis of target compounds.In the future project, this LSI ionization should be applied to a nanoscale LC system to obtain more stable ionization.