液相色谱-串联质谱法测定托吡酯的治疗药物监测。
Therapeutic drug monitoring of topiramate by liquid chromatography-tandem mass spectrometry.
机构信息
Department of Applied Therapeutics, Faculty of Pharmacy, Kuwait University, Safat, Kuwait.
出版信息
Clin Chim Acta. 2010 May 2;411(9-10):729-34. doi: 10.1016/j.cca.2010.02.003. Epub 2010 Feb 6.
BACKGROUND
Topiramate (TPM) is a new antiepileptic drug (AED) used worldwide in patients with various types of epilepsies and also for prophylaxis of migraine. A rapid, selective, reliable, precise, accurate, and reproducible tandem mass spectrometric (MS/MS) method for quantification of TPM in human plasma using topiramate-d12 as an internal standard (IS) has been developed and validated to be used routinely for TDM of TPM.
METHODS
The drug and IS were extracted by ether and analyzed on Symmetry C18 column. Quantitation was achieved using ESI-interface employing MRM mode.
RESULTS
The method was validated over the concentration range of 0.5-30 microg/ml (r>0.99). Intra- and inter-run precisions of TPM assay at three concentrations ranged from 0.7 to 7.8% with accuracy (bias) varied from -10.0 to 2.1% indicating good precision and accuracy. Analytical recoveries of TPM and IS from spiked human plasma were in the range of 84.1 to 90.0% and 90.0 to 111.0%, respectively. Stability of TPM in human plasma samples at different conditions showed that the drug was stable under the studied conditions. Matrix effect study showed a lack of matrix effect on mass ions of TPM and IS.
CONCLUSION
The described method compared well when assessed by Heathcontrol TDM theme program (r>0.99). The suitability of the developed method for TDM was demonstrated by measuring TPM in human plasma samples of epileptic patients treated with TPM. The proposed method is appropriate for routine TDM of TPM.
背景
托吡酯（TPM）是一种新的抗癫痫药物（AED），在世界各地广泛用于治疗各种类型的癫痫，也用于偏头痛的预防。本研究建立并验证了一种快速、选择性、可靠、精确、准确和重现性的人血浆中托吡酯的串联质谱（MS/MS）定量分析方法，该方法采用托吡酯-d12 作为内标（IS），可用于 TPM 的常规治疗药物监测（TDM）。
方法
采用乙醚提取药物和 IS，在 Symmetry C18 柱上进行分析。采用 ESI-接口，以 MRM 模式进行定量。
结果
该方法在 0.5-30μg/ml 浓度范围内验证（r>0.99）。在三个浓度下，TPM 测定的日内和日间精密度在 0.7-7.8%范围内，准确度（偏差）在-10.0-2.1%之间，表明精密度和准确度良好。TPM 和 IS 从人血浆中提取的回收率分别在 84.1-90.0%和 90.0-111.0%范围内。在不同条件下，人血浆样品中 TPM 的稳定性研究表明，该药物在研究条件下稳定。基质效应研究表明，TPM 和 IS 的基质效应缺乏。
结论
通过 Heathcontrol TDM 主题方案评估，该方法表现良好（r>0.99）。通过测量接受 TPM 治疗的癫痫患者的人血浆样品中的 TPM，证明了所开发方法用于 TDM 的适用性。该方法适用于 TPM 的常规 TDM。
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