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Quantitative and qualitative analysis of CKD-501, lobeglitazone, in human plasma and urine using LC-MS/MS and its application to a pharmacokinetic study

机译:LC-MS / MS对人血浆和尿液中CKD-501,洛贝格列酮的定量和定性分析及其在药代动力学研究中的应用

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Asimple, rapid and sensitive LC-MS/MSmethod in positive ionmode was developed and validated to determine CKD-501, lobeglitazone, in human plasma and urine using glipizide as an internal standard (IS). Lobeglitazone is a novel thiazolidinedione (TZDs)-based peroxisome proliferatoractivated receptor (PPAR) agonist, used for themanagementof type-2 diabetes. After mixing the IS, dissolved in acetonitrile, with a plasma or urine sample containing lobeglitazone, 10 μL of supernatant was injected into the LC-MS/MS system. Quantification was performed in the multiple reaction monitoring (MRM) mode using transition of 481.5 → 152.2 (m/z) for lobeglitazone and 446.1 → 321.2 (m/z) for the IS. The method showed good linearity over concentration ranges of 0.5-1,000 ng mL ~(-1) for plasma and 0.2-250 ng mL ~(-1) for urine (r ~2 ≥ 0.9996). The mean percent extraction recovery of lobeglitazone was 90.8 % for plasma and 87.3 % for urine, while the recoveries of the IS were greater than 86.4 % for both. The intra-day and inter-day precision of plasma ranged from 1.1 to 3.7 and 2.5 to 3.3 % (RSD), respectively, and the intra- and inter-day precision of urine ranged from 1.5 to 2.7 and 3.2 to 3.5 %, respectively. This method is simple, sensitive, and applicable for the pharmacokinetic study of lobeglitazone in human plasma. Most of the urine concentrations of lobeglitazone were below the LLOQ because the lobeglitazone is extensively metabolized.
机译:开发了正离子模式的简便,快速,灵敏的LC-MS / MS方法,并验证了使用格列吡嗪作为内标(IS)测定人血浆和尿液中的CKD-501,洛贝格列酮的有效性。洛贝格列酮是一种新型的基于噻唑烷二酮(TZDs)的过氧化物酶体增殖物激活受体(PPAR)激动剂,用于治疗2型糖尿病。将溶于乙腈的IS与含有洛贝格列酮的血浆或尿液样品混合后,将10μL上清液注入LC-MS / MS系统。在多反应监测(MRM)模式下进行定量,洛贝格列酮的转换为481.5→152.2(m / z),IS的转换为446.1→321.2(m / z)。该方法在血浆浓度范围为0.5-1,000 ng mL〜(-1)和尿液浓度为0.2-250 ng mL〜(-1)时显示出良好的线性(r〜2≥0.9996)。洛贝格列酮的血浆平均提取回收率为90.8%,尿液的回收率为87.3%,而两者的IS回收率均大于86.4%。血浆的日间和日间精度分别为1.1%至3.7%和2.5%至3.3%(RSD),尿液的日间和日间精度分别为1.5%至2.7%和3.2%至3.5% 。该方法简便,灵敏,可用于洛贝格列酮在人血浆中的药代动力学研究。雷贝格列酮的大部分尿液浓度均低于LLOQ,因为该氯贝格列酮被广泛代谢。

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