使用气相色谱-质谱仪/质谱仪测定大鼠血浆中 AMB-FUBINACA 的药代动力学（半衰期、分布容积和清除率）。

IF 1.3 4区医学 Q4 PHARMACOLOGY & PHARMACY

Journal of pharmacological and toxicological methods Pub Date : 2024-05-01 DOI:10.1016/j.vascn.2024.107513

Elkhatim Hassan Abdelgadir , Sarah Dafer Alshehri , Sachil Kumar

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引用次数: 0

摘要

背景：最近，包括 2-(1-(4-氟苄基)-1-吲唑-3-甲酰胺基)-3-甲基丁酸甲酯（AMB-FUBINACA）在内的几种新型合成大麻素出现在非法药物市场上。为了确定 AMB-FUBINACA 在大鼠血浆中的药代动力学特性（半衰期、分布容积和清除率），我们开发了一种简单、快速和高灵敏度的分析方法：方法：18 只 Wistar 大鼠分为两组：一组为对照组（生理盐水载体），另一组为治疗组（50 毫克/千克的 AMB-FUBINACA）。在注射前（t = 0）和注射后 30、60、90、120 和 240 分钟通过导管抽取血液样本（400 μL）。将样本收集到 1 mL 结核菌素注射器中，然后转移到装有 5 μl 1000 IU/mL K3-EDTA （Thomas Scientific 公司）的 1.5 mL 塑料管中。将装有样本的 EDTA 管放入离心机中，在 4 °C 下以 1000 g 离心 10 分钟。上层为血浆馏分，将其倒入低温瓶中，保存在 -20 °C 下，直至分析。对气相色谱-串联质谱（GC-MS/MS）方法进行了优化和验证，并结合液液萃取对大鼠血浆中的 AMB-FUBINACA 进行了分析：该研究方法成功地满足了美国食品药品管理局（FDA）的验证要求，在0.5-1000 ng/ml的浓度范围内具有良好的选择性和线性校正曲线。相关系数（r2）为 0.99，表明线性关系很强。确定分析物的定量限（LOQ）为 1-5 纳克/毫升。随后，该方法被成功地应用于研究大鼠血液样本中AMB-FUBINACA的药代动力学。大鼠口服 AMB-FUBINACA 后吸收迅速，血浆半衰期（t1/2）为 5.91 h，分布容积（Vd）为 203.13 l，血浆清除率为 23.81122 L/h：这些发现有助于了解 AMB-FUBINACA 的药代动力学和药效学。

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Determine the pharmacokinetics (half-life, volume of distribution and clearance) of AMB-FUBINACA in rats plasma using GC–MS / MS

Background

Several novel synthetic cannabinoids, including methyl 2-(1-(4-fluorobenzyl)-1Hindazole-3-carboxamido)-3-methylbutanoate (AMB-FUBINACA), have recently surfaced on the illicit drug market. To determine the pharmacokinetic properties (half-life, volume of distribution, and clearance) of AMB-FUBINACA in rats plasma, a straightforward, quick, and highly sensitive analytical approach was developed.

Methods

Eighteen Wistar rats were divided into two groups: one control (saline vehicle) and one treatment group (AMB-FUBINACA at 50 mg/kg). Blood samples (400 μL) were withdrawn via catheters immediately before (t = 0) and at 30, 60, 90, 120, and 240 min following injection. Samples were collected into 1 mL tuberculin syringes, then transferred to 1.5 mL plastic tubes containing 5 μL of 1000 IU/mL K3-EDTA (Thomas Scientific). Place the EDTA tubes containing samples in a centrifuge and spin at 1000 g for 10 min at 4 °C. The top layer is the plasma fraction, which is decanted into cryovials and stored at −20 °C until analysis. The gas chromatography tandem mass spectrometry (GC–MS/MS) method was optimized and validated, combined with liquid-liquid extraction, to analyze AMB-FUBINACA in rat plasma.

Results

The research method successfully met the validation requirements set by the FDA, demonstrating selectivity and linear calibration curves within a concentration range of 0.5–1000 ng/ml. The correlation coefficient (r2) was determined to be 0.99, indicating a strong linear relationship. The analyte's limit of quantitation (LOQ) was determined to be 1–5 ng/mL. Subsequently, the method was successfully applied to investigate the pharmacokinetics of AMB-FUBINACA in rats' blood samples. Following oral administration, AMB-FUBINACA was rapidly absorbed, with a plasma half-life (t1/2) of 5.91 h, a volume of distribution (Vd) of 203.13 l, and a plasma clearance of 23.81122 L/h.

Conclusion

These findings contribute to the understanding of AMB-FUBINACA's pharmacokinetics and pharmacodynamics.

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来源期刊

Journal of pharmacological and toxicological methods PHARMACOLOGY & PHARMACY-TOXICOLOGY

CiteScore

3.60

自引率

10.50%

发文量

审稿时长

26 days

期刊介绍： Journal of Pharmacological and Toxicological Methods publishes original articles on current methods of investigation used in pharmacology and toxicology. Pharmacology and toxicology are defined in the broadest sense, referring to actions of drugs and chemicals on all living systems. With its international editorial board and noted contributors, Journal of Pharmacological and Toxicological Methods is the leading journal devoted exclusively to experimental procedures used by pharmacologists and toxicologists.