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

质谱（MS）是检测和鉴定药物和毒物的有用工具;最近接口的进展使高效液相色谱（LC）能够耦合为LC/MS或LC/MS/MS。电喷雾电离（ESI）被广泛用作LC/MS的电离方法，但需要更高效率的更软的电离方法。本课题尝试将激光电离（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，利用红外激光束电离目标化合物，在本项目中，最困难的问题之一是激光束在毛细管尖端的适当调整;光路的延长和使用CCD照相机对毛细管的监测对于毛细管尖端上的激光焦点的费用调整是有用的。我们使用飞行时间（TOF）MS作为LC/MS系统，飞行时间质谱具有较高的质量分辨率;我们已经开发了一种灵敏和特异的方法来鉴定和定量人体体液和块茎中的生物碱，该方法将发表在Journal of Mass Spectrometry上。通过LSI，一些滥用药物，例如可卡因，吗啡和安非他明以5到10倍的高强度电离，与传统的ESI相比。在负离子模式下，丙酸衍生物镇痛-解热化合物的电离强度比ESI高20至30倍。所有化合物均采用直接输注方式。但由于离子强度不稳定，给目标化合物的在线分析带来困难，在未来的项目中，这种LSI离子化方法应该应用于纳米LC系统，以获得更稳定的离子化。

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.