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一种用于定量血浆中加巴喷丁的液相色谱-串联质谱法的开发与验证:在猫体内药代动力学研究中的应用

Development and Validation of an LC-MS/MS Method for Quantifying Gabapentin in Plasma: Application to a Pharmacokinetic Study in Cats.

作者信息

Zhao Feifei, Lin Changcheng, Wu Yunying, Luo Xinyue, Han Ning, Xiong Wenguang, Zeng Zhenling

机构信息

Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.

National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, Guangzhou 510642, China.

出版信息

Animals (Basel). 2025 Mar 26;15(7):950. doi: 10.3390/ani15070950.

Abstract

Gabapentin (GBP), a γ-aminobutyric acid analogue used for neuropathic pain and epilepsy, can reduce cat stress and improve veterinary exam compliance. A sensitive LC-MS/MS assay was established and rigorously validated for quantifying GBP in feline plasma. The method employed acetonitrile-mediated protein precipitation to efficiently extract GBP and its internal standard, pregabalin (PGB). Chromatographic separation was achieved within 7 min using a C18 column (2.1 × 50 mm, 1.7 μm) with a gradient mobile phase comprising 0.1% (/) formic acid in water and acetonitrile. The pharmacokinetics of 25  mg/kg GBP was studied by single-dose oral and intravenous administration. The results demonstrated that the method exhibited satisfactory precision, accuracy and linearity. The pharmacokinetic results showed that the T, C, T and AUC of GBP in cats after oral administration of 25  mg/kg were (1.83 ± 0.75) h, (13.94 ± 3.75) μg/mL, (5.60 ± 1.79) h and (115.54 ± 27.56) (μg/mL) h, respectively. The results of the study indicated that after intravenous administration of 25 mg/kg GBP, the C, T and AUC were (58.82 ± 15.34) μg/mL, (3.87 ± 0.64) h and (160.44 ± 32.65) (μg/mL) h, respectively. The oral bioavailability of GBP in cats was (78.71 ± 18.55)%. In this study, a selective and sensitive LC-MS/MS method for the quantification of GBP in cat plasma was developed and validated. This method was successfully employed to assess the pharmacokinetics following the oral and intravenous administration of GBP in cats.

摘要

加巴喷丁(GBP)是一种用于治疗神经性疼痛和癫痫的γ-氨基丁酸类似物,它可以减轻猫的应激反应并提高兽医检查的依从性。建立了一种灵敏的液相色谱-串联质谱(LC-MS/MS)测定法,并对其进行了严格验证,用于定量猫血浆中的GBP。该方法采用乙腈介导的蛋白沉淀法有效提取GBP及其内标普瑞巴林(PGB)。使用C18柱(2.1×50 mm,1.7μm),以含0.1%(/)甲酸的水和乙腈组成的梯度流动相,在7分钟内实现色谱分离。通过单剂量口服和静脉给药研究了25 mg/kg GBP的药代动力学。结果表明,该方法具有令人满意的精密度、准确度和线性。药代动力学结果显示,猫口服25 mg/kg GBP后的T、C、T和AUC分别为(1.83±0.75)小时、(13.94±3.75)μg/mL、(5.60±1.79)小时和(115.54±27.56)(μg/mL)·小时。研究结果表明,静脉注射25 mg/kg GBP后,C、T和AUC分别为(58.82±15.34)μg/mL、(3.87±0.64)小时和(160.44±32.65)(μg/mL)·小时。GBP在猫体内的口服生物利用度为(78.71±18.55)%。在本研究中,开发并验证了一种用于定量猫血浆中GBP的选择性灵敏LC-MS/MS方法。该方法成功用于评估猫口服和静脉注射GBP后的药代动力学。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20be/11988044/93bf52ff98eb/animals-15-00950-g001.jpg

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