Shibata Masaaki, Takahashi Masaaki, Yoshino Munehiro, Kuwahara Takeshi, Nomura Toshiharu, Yokomaku Yoshiyuki, Sugiura Wataru
Department of Pharmacy, National Hospital Organization Nagoya Medical Center, Aichi, Japan.
J Med Invest. 2013;60(1-2):35-40. doi: 10.2152/jmi.60.35.
Rilpivirine (TMC-278) is a second-generation non-nucleoside reverse transcriptase inhibitor that is high potent against both wild-type and drug-resistant HIV-1 strains. Therefore, rilpivirine is expected to treat therapy-experienced patients who failed to use current drugs due to the emergence of drug-resistant HIV mutants. The quantification of rilpivirine in human plasma is important to support clinical studies and determine pharmacokinetic parameters of rilpivirine in HIV-1 infected patients. Consequently, simple and easy system to determine plasma rilpivirine concentrations has been required. In this study, we developed a conventional LC-MS method to quantify plasma rilpivirine. Subsequently the method was validated by estimating the precision and accuracy for inter- and intraday analysis in the concentration range of 18-715 ng/ml. The calibration curve was linear in this range. Average accuracy ranged from 100.0 to 100.6%. Relative standard deviations of both inter- and intraday assays were less than 3.3%. Recovery of rilpivirine was more than 82.0%. These results demonstrate that our LC-MS method provides a conventional, accurate and precise way to determine rilpivirine in human plasma. This method can be used in routine clinical application for HIV-1 infected patients, and permits management of drug interactions and toxicity for rilpivirine.
利匹韦林（TMC-278）是一种第二代非核苷类逆转录酶抑制剂，对野生型和耐药HIV-1毒株均具有高效活性。因此，利匹韦林有望用于治疗那些因出现耐药HIV突变体而无法使用现有药物的经治患者。测定人体血浆中的利匹韦林含量对于支持临床研究以及确定HIV-1感染患者体内利匹韦林的药代动力学参数至关重要。因此，需要一种简单易行的系统来测定血浆中利匹韦林的浓度。在本研究中，我们开发了一种常规的液相色谱-质谱（LC-MS）方法来定量测定血浆中的利匹韦林。随后，通过评估浓度范围为18 - 715 ng/ml的日内和日间分析的精密度和准确度对该方法进行了验证。在此范围内校准曲线呈线性。平均准确度在100.0%至100.6%之间。日内和日间测定的相对标准偏差均小于3.3%。利匹韦林的回收率超过82.0%。这些结果表明，我们的LC-MS方法为测定人体血浆中的利匹韦林提供了一种常规、准确且精密的方法。该方法可用于HIV-1感染患者的常规临床应用，并有助于管理利匹韦林的药物相互作用和毒性。
