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一种无需萃取的高效液相色谱-串联质谱法用于检测和定量犬血浆中罗格列酮的评估。

Evaluation of an extractionless high-performance liquid chromatography-tandem mass spectrometry method for detection and quantitation of rosiglitazone in canine plasma.

作者信息

Frazier Sara Allstadt, McKemie Daniel S, Guerrero Teri A, Skorupski Katherine A, Rodriguez Carlos O

机构信息

Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616, USA.

出版信息

Am J Vet Res. 2011 Feb;72(2):263-70. doi: 10.2460/ajvr.72.2.263.

DOI:10.2460/ajvr.72.2.263
PMID:21281203
Abstract

OBJECTIVE

To develop a simple extractionless method for detection of rosiglitazone in canine plasma and test the method in a pharmacokinetic study after oral administration of rosiglitazone in dogs.

ANIMALS

3 client-owned dogs with cancer.

PROCEDURES

High-performance liquid chromatography-tandem mass spectrometry was performed on canine plasma. The 3 dogs with cancer in the pharmacokinetic study were assessed via physical examination and clinicopathologic evaluation and considered otherwise healthy. Food was withheld for 12 hours, and dogs were administered a single dose (4 mg/m²) of rosiglitazone. Plasma was collected at various times, processed, and analyzed for rosiglitazone.

RESULTS

The developed method was robust and detected a minimum of 0.3 ng of rosiglitazone/mL. Mean ± SD maximum plasma concentration was 205.2 ± 79.1 ng/mL, which occurred at 3 ± 1 hours, and mean ± SD elimination half-life was 1.4 ± 0.4 hours. The area under the plasma rosiglitazone concentration-versus-time curve varied widely among the 3 dogs (mean ± SD, 652.2 ± 351.3 ng/h/mL).

CONCLUSIONS AND CLINICAL RELEVANCE

A simple extractionless method for detection of rosiglitazone in canine plasma was developed and was validated with excellent sensitivity, accuracy, precision, and recovery. The method enabled unambiguous evaluation and quantitation of rosiglitazone in canine plasma. This method will be useful for pharmacokinetic, bioavailability, or drug-drug interaction studies. Oral rosiglitazone administration was well tolerated in the dogs.

摘要

目的

开发一种简单的无需萃取的方法来检测犬血浆中的罗格列酮,并在犬口服罗格列酮后的药代动力学研究中对该方法进行测试。

动物

3只患癌症的客户拥有的犬。

步骤

对犬血浆进行高效液相色谱-串联质谱分析。在药代动力学研究中,对3只患癌症的犬进行体格检查和临床病理评估,认为它们在其他方面健康。禁食12小时后,给犬单次服用一剂(4 mg/m²)罗格列酮。在不同时间采集血浆,进行处理并分析罗格列酮。

结果

所开发的方法稳健,最低可检测到0.3 ng罗格列酮/mL。平均±标准差最大血浆浓度为205.2±79.1 ng/mL,出现在3±1小时,平均±标准差消除半衰期为1.4±0.4小时。3只犬的血浆罗格列酮浓度-时间曲线下面积差异很大(平均±标准差,652.2±351.3 ng/h/mL)。

结论及临床意义

开发了一种简单的无需萃取的方法来检测犬血浆中的罗格列酮,并通过出色的灵敏度、准确性、精密度和回收率进行了验证。该方法能够明确评估和定量犬血浆中的罗格列酮。此方法将有助于药代动力学、生物利用度或药物相互作用研究。犬口服罗格列酮耐受性良好。

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