Elucidation of Degradation Behavior of Nitrazepam, a Benzodiazepine Drug, under Basic Conditions: Study on Degradability of Drugs in Stomach (IV)

IF 1.5 4区医学 Q4 CHEMISTRY, MEDICINAL

Chemical & pharmaceutical bulletin Pub Date : 2024-01-01 DOI:10.1248/cpb.c23-00626

Koichi Saito, Mai Yokota, Rie Ito, Miho Sakamoto, Kimio Higashiyama

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Abstract

This study investigates the stability of nitrazepam (NZP), a benzodiazepine drug, under basic conditions, since alkaline putrefactive amines and ammonia are produced once bodies are left to decompose for a long period postmortem after a murder involving NZP or an accidental overdose of NZP. The degradation of NZP in an aqueous alkaline solution was investigated by LC/photodiode array detector (PDA) where the NZP degradation product was isolated and purified by solid-phase extraction using Oasis^® MCX, and its chemical structure was determined by LC/time-of-flight (TOF)-MS, NMR spectroscopy, and single-crystal X-ray crystallography. The results revealed that NZP was immediately degraded under basic conditions with 2-amino-5-nitrobenzophenone being an intermediate which further degraded to provide 2-hydroxy-5-nitrobenzophenone as the final degradation product. These results are expected to be useful in clinical chemistry and forensic science, such as the detection of drugs during postmortem examination and suspected addiction.

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阐明苯二氮卓类药物硝西泮在基本条件下的降解行为：药物在胃中的降解性研究（IV）

本研究调查了苯二氮卓类药物硝西泮（NZP）在碱性条件下的稳定性，因为在涉及 NZP 的谋杀案或意外过量服用 NZP 后，一旦尸体在死后长时间腐烂，就会产生碱性腐胺和氨。通过液相色谱/光电二极管阵列检测器（PDA）研究了 NZP 在碱性水溶液中的降解过程，使用 Oasis® MCX 进行固相萃取，分离和纯化了 NZP 降解产物，并通过液相色谱/飞行时间质谱（TOF）、核磁共振光谱和单晶 X 射线晶体学测定了其化学结构。结果表明，NZP 在碱性条件下会立即降解，中间产物为 2-氨基-5-硝基二苯甲酮，进一步降解后的最终降解产物为 2-羟基-5-硝基二苯甲酮。这些结果有望在临床化学和法医学中发挥作用，例如在尸检中检测毒品和疑似吸毒上瘾。

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来源期刊

Chemical & pharmaceutical bulletin 医学-化学综合

CiteScore

3.20

自引率

5.90%

发文量

132

审稿时长

1.7 months

期刊介绍： The CPB covers various chemical topics in the pharmaceutical and health sciences fields dealing with biologically active compounds, natural products, and medicines, while BPB deals with a wide range of biological topics in the pharmaceutical and health sciences fields including scientific research from basic to clinical studies. For details of their respective scopes, please refer to the submission topic categories below. Topics: Organic chemistry In silico science Inorganic chemistry Pharmacognosy Health statistics Forensic science Biochemistry Pharmacology Pharmaceutical care and science Medicinal chemistry Analytical chemistry Physical pharmacy Natural product chemistry Toxicology Environmental science Molecular and cellular biology Biopharmacy and pharmacokinetics Pharmaceutical education Chemical biology Physical chemistry Pharmaceutical engineering Epidemiology Hygiene Regulatory science Immunology and microbiology Clinical pharmacy Miscellaneous.