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验证的高效液相色谱法同时测定大鼠血浆中罗格列酮、西洛他唑和3,4-脱氢西洛他唑及其在药代动力学中的应用

Validated high performance liquid chromatographic method for simultaneous determination of rosiglitazone, cilostazol, and 3,4-dehydro-cilostazol in rat plasma and its application to pharmacokinetics.

作者信息

Varanasi V S Kanthi Kiran, Veeraraghavan Sridhar, Potharaju Suresh, Thappali R S Satheeshmanikandan, Raghavan Rashmi, Vakkalanka V S Swaroop Kumar

机构信息

Division of Pharmacokinetics and Drug Metabolism, Glenmark Research Centre, Mahape, Navi Mumbai, India.

出版信息

Arzneimittelforschung. 2008;58(6):288-96. doi: 10.1055/s-0031-1296509.

Abstract

A high performance liquid chromatographic (HPLC) method for simultaneous determination of rosiglitazone, CAS 122320-73-4, RSG), cilostazol (CAS 73963-72-1, CLZ) and its active metabolite 3, 4-dehydro-cilostazol (DCLZ), using pioglitazone (PIO) as internal standard (IS), in rat plasma is described. The plasma was extracted with methyl t-butyl ether, the dry extract was reconstituted in mobile phase and the aliquot was injected. The eluent drugs were detected by UV at dual wavelength of 226 nm (RSG and DCLZ) and 257 nm (CLZ). The mobile phase consisting of acetonitrile:potassium di-hydrogen phosphate buffer (35:65 v/v) was used at the flow rate of 1.2 ml/min on a reverse phase C18 column. The absolute recovery was above 90% of all analytes over the concentration range of 25-2500 ng/ml for RSG and CLZ and 20-2000 ng/ ml for DCLZ. The relative standard deviation (RSD) of the inter-day and intra-day precision ranged from 2.8 to 8.4% and 0.9 to 5.9%, respectively. The method is simple, rapid, accurate and sensitive and was applied to pharmacokinetic studies.

摘要

本文描述了一种高效液相色谱(HPLC)法,该方法以吡格列酮(PIO)为内标(IS),用于同时测定大鼠血浆中的罗格列酮(CAS 122320-73-4,RSG)、西洛他唑(CAS 73963-72-1,CLZ)及其活性代谢物3,4-脱氢西洛他唑(DCLZ)。血浆用甲基叔丁基醚萃取,干燥提取物用流动相复溶,然后进样。通过在226 nm(RSG和DCLZ)和257 nm(CLZ)的双波长下进行紫外检测洗脱的药物。流动相由乙腈:磷酸二氢钾缓冲液(35:65 v/v)组成,在反相C18柱上以1.2 ml/min的流速使用。对于RSG和CLZ,在25-2500 ng/ml的浓度范围内,所有分析物的绝对回收率均高于90%;对于DCLZ,在20-2000 ng/ml的浓度范围内,所有分析物的绝对回收率均高于90%。日间和日内精密度的相对标准偏差(RSD)分别为2.8%至8.4%和0.9%至5.9%。该方法简单、快速、准确且灵敏,已应用于药代动力学研究。

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