UPLC-MS/MS快速定性定量分析血液中依托咪酯及其结构类似物并在6例法医病例中的应用

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis Pub Date : 2025-05-15 DOI:10.1016/j.jpba.2025.116962

Xiaoyu Qian , Liying Zhou , Xin Wang , Huosheng Qiang , Jian Li , Ping Xiang , Hui Yan

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引用次数: 0

摘要

依托咪酯及其结构类似物的滥用日益严重，对公共安全构成重大威胁。本研究旨在建立一种超高效液相色谱-三重四极杆串联质谱（UPLC-MS/MS）同时定量测定人血液中依托咪酯、甲咪酯、异丙酸、丙酸和依托咪酯酸的方法。方法：取1 mL空白血样，加入3 µL 100 ng/mL内标液和3 mL乙醚，旋流、离心，干燥、再溶解上清进行分析。血液样品中依托咪酯及其结构类似物在0.1 ~ 10 ng/mL范围内、依托咪酯酸在1 ~ 100 ng/mL范围内的校正曲线相关系数(r)均大于0.999。依托咪酯及其结构类似物的检测限（LOD）和定量限（LOQ）分别为0.05 ng/mL和0.1 ng/mL。依托咪酯酸的定量限和定量限分别为0.5 ng/mL和1 ng/mL。精密度、准确度、回收率、基质效应和稀释度完整性均满足验证要求。建立并验证了血液样品中依托咪酯及其结构类似物的定量分析方法，实现了丙酸酯和异丙酸酯异构体的分离。此外，该方法还成功地应用于法医案件中的6份真实血液样本。

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Rapid qualitative and quantitative analysis of etomidate and its structural analogs in blood by UPLC-MS/MS and application in six forensic cases

Etomidate and its structural analogs have been increasingly abused, posing significant risks to public safety. This study aimed to develop an ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of etomidate, metomidate, isopropoxate, propoxate, and etomidate acid in human blood. The method involved taking 1 mL of a blank blood sample, adding 3 µL of 100 ng/mL internal standard solution and 3 mL of diethyl ether, vortexing, centrifuging, and then drying and redissolving the supernatant for analysis. The correlation coefficient (r) values of the calibration curves for etomidate and its structural analogs in blood samples in the range of 0.1–10 ng/mL and etomidate acid in the range of 1–100 ng/mL were all greater than 0.999. The limit of detection (LOD) and limit of quantitation (LOQ) of etomidate and its structural analogs were 0.05 ng/mL and 0.1 ng/mL, respectively. The LOD and LOQ of etomidate acid were 0.5 ng/mL and 1 ng/mL, respectively. Precision, accuracy, recovery, matrix effect, and dilution integrity met the validation requirements. The method for quantitative analysis of etomidate and its structural analogs in blood samples was established and validated, enabling the separation of the isomers propoxate and isopropoxate. In addition, the method was successfully applied to six real blood samples in forensic cases.

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来源期刊

Journal of pharmaceutical and biomedical analysis 医学-分析化学

CiteScore

6.70

自引率

5.90%

发文量

588

审稿时长

37 days

期刊介绍： This journal is an international medium directed towards the needs of academic, clinical, government and industrial analysis by publishing original research reports and critical reviews on pharmaceutical and biomedical analysis. It covers the interdisciplinary aspects of analysis in the pharmaceutical, biomedical and clinical sciences, including developments in analytical methodology, instrumentation, computation and interpretation. Submissions on novel applications focusing on drug purity and stability studies, pharmacokinetics, therapeutic monitoring, metabolic profiling; drug-related aspects of analytical biochemistry and forensic toxicology; quality assurance in the pharmaceutical industry are also welcome. Studies from areas of well established and poorly selective methods, such as UV-VIS spectrophotometry (including derivative and multi-wavelength measurements), basic electroanalytical (potentiometric, polarographic and voltammetric) methods, fluorimetry, flow-injection analysis, etc. are accepted for publication in exceptional cases only, if a unique and substantial advantage over presently known systems is demonstrated. The same applies to the assay of simple drug formulations by any kind of methods and the determination of drugs in biological samples based merely on spiked samples. Drug purity/stability studies should contain information on the structure elucidation of the impurities/degradants.