Estimation of plasma levels of warfarin and 7-hydroxy warfarin by high performance liquid chromatography in patients receiving warfarin therapy
Estimation of plasma levels of warfarin and 7-hydroxy warfarin by high performance liquid chromatography in patients receiving warfarin therapy
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DOI：
10.1016/j.jyp.2013.02.001
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发表时间：
2013-01-01
影响因子：
0.4
通讯作者：
Adithan, Chandrasekaran
中科院分区：
文献类型：
--
作者：
Kumar, Dhakchinamoorthi Krishna;Shewade, Deepak Gopal;Adithan, Chandrasekaran
华法林是预防血栓栓塞症最常用的口服抗凝剂之一。通过监测以国际标准化比率(INR)表示的凝血酶原时间来衡量该药物的效果。然而，在某些情况下，强调了华法林血药浓度的测量。采用反相高效液相色谱(HPLC法)测定血药浓度。本研究共纳入185例患者。用EDTA钠管采集5毫升静脉血进行药代动力学分析。采用固相萃取法，以异丙醇-磷酸二氢钾缓冲液(40：60)为流动相，从血浆中回收华法林及其代谢物。采用C18色谱柱分离华法林、7-羟基华法林和卡马西平内标，保留时间分别为3.6min、2.9min和5.9min。该方法在0.1~5ug/ml浓度范围内线性关系良好，提取回收率接近或等于85%。平均血药浓度分别为3.47+/-1.87(SD)mg/ml和1.25+/-0.81(SD)mg/ml。通过本研究，测定了华法林、7-羟基华法林的血药浓度及其代谢率。该检测对一名接受华法林治疗3个月以上的患者的华法林药代动力学是敏感的。版权所有(C)2013，印度医药协会，Reed Elsevier India Pvt.Ltd.出版。保留所有权利。
Warfarin is one of the most commonly prescribed oral anticoagulant for prevention of thromboembolic events. The effect of this drug is measured by monitoring prothrombin time expressed as International Normalized Ratio (INR). In some cases, however, the measurement of plasma concentration of warfarin was emphasized. In the present study, reversed phase high performance liquid chromatography (HPLC) was used to estimate the plasma drug levels. A total of 185 patients were enrolled in this study. Five milliliter of venous blood was collected using sodium EDTA tubes for pharmacokinetic analysis. Solid phase extraction was used to recover the warfarin and it's metabolite from plasma using isopropanol and potassium phosphate buffer (40: 60) mobile phase. Warfarin, 7-hydroxy warfarin and carbamazepine (internal standard) were separated on a C18 column and had the retention time 3.6 min, 2.9 min and 5.9 min, respectively. The assay was linear in warfarin concentration ranges of 0.1-5 mu g/ml. The extraction recovery was found to be similar or equal to 85%. The mean plasma concentrations of warfarin and 7-hydroxy warfarin were found to be 3.47 +/- 1.87 (SD) mg/ml, 1.25 +/- 0.81 (SD) mg/ml, respectively. Through the present study the plasma concentrations of warfarin, 7-hydroxy warfarin and their metabolic ratio was determined. The assay was sensitive to follow warfarin pharmacokinetics in a patient with warfarin therapy for 3 months and above. Copyright (C) 2013, InPharm Association, Published by Reed Elsevier India Pvt. Ltd. All rights reserved.