Sano T, Sato K, Kurihara R, Mizuno Y, Kojima T, Yamakawa Y, Yamada T, Ishii A, Katsumata Y
Department of Legal Medicine and Bioethics, Nagoya University Graduate School of Medicine, Japan.
Leg Med (Tokyo). 2001 Sep;3(3):149-56. doi: 10.1016/s1344-6223(01)00023-2.
Midazolam is a benzodiazepine and is widely prescribed for preanesthesia or general anesthesia. Overdose or intoxication cases of midazolam have been reported. In Japan, smuggled midazolam tablets could be involved in some criminal cases. Midazolam and its two metabolites were extracted by the solid-phase extraction method using Bond Elut SCX cartridges. The compounds were analyzed by on-line capillary high-performance liquid chromatography/fast atom bombardment-mass spectrometry. Midazolam and its two metabolites were well separated on the chromatogram, and each mass spectra gave M+H ion as a base peak. Deuterium-labeled midazolam was synthesized as an internal standard; it has enabled precise and reproducible quantitation of midazolam in blood samples. The calibration curve showed excellent linearity in the range of 2-200 ng/ml in spiked serum. The detection limit was 300 pg/ml (signal-to-noise ratio=3). The whole blood and urine samples from the victim of a homicide case were analyzed, and the midazolam concentration in the whole blood was estimated to be 163 ng/ml. The present method should be useful in clinical and forensic toxicology, because of its high sensitivity and specificity.
咪达唑仑是一种苯二氮䓬类药物，广泛用于麻醉前或全身麻醉。已有咪达唑仑过量或中毒的病例报道。在日本，走私的咪达唑仑片剂可能涉及一些刑事案件。使用Bond Elut SCX柱通过固相萃取法提取咪达唑仑及其两种代谢物。采用在线毛细管高效液相色谱/快原子轰击质谱法对这些化合物进行分析。咪达唑仑及其两种代谢物在色谱图上得到了很好的分离，每个质谱图均以M+H离子作为基峰。合成了氘代咪达唑仑作为内标；它能够对血样中的咪达唑仑进行精确且可重复的定量。在加标的血清中，校准曲线在2 - 200 ng/ml范围内显示出良好的线性。检测限为300 pg/ml（信噪比 = 3）。对一起凶杀案受害者的全血和尿液样本进行了分析，估计全血中咪达唑仑浓度为163 ng/ml。由于其高灵敏度和特异性，本方法在临床和法医毒理学中应具有实用价值。
