Determination of Oxaliplatin by a UHPLC-MS/MS Method: Application to Pharmacokinetics and Tongue Tissue Distribution Studies in Rats.
Determination of Oxaliplatin by a UHPLC-MS/MS Method: Application to Pharmacokinetics and Tongue Tissue Distribution Studies in Rats.
复制标题
DOI：
10.3390/ph15010052
复制
发表时间：
2021-12-31
期刊：
影响因子：
--
通讯作者：
Xie H
中科院分区：
文献类型：
--
作者：
Gao X;Tsai RYL;Ma J;Wang Y;Liu X;Liang D;Xie H
奥沙利铂(OXP)是第三代铂类化疗药物，由于其不稳定、柱分离性差、MS信号抑制严重，采用LC-MS/MS方法难以直接定量，常采用电感耦合等离子体质谱(ICP-MS)通过全铂间接分析。在此，我们建立并验证了一种特异、灵敏和重现性好的LC-MS/MS方法，用于在SCIEX 4000QTRAP®MS/MS系统上定量测定大鼠血浆和舌组织中的OXP本身。方法的检出限和定量下限分别为5 ng/m L和10 ng/m L，线性范围分别为10-5000 ng/m L(R2>；0.99)和10-2500 ng/m L(R2>；0.99)。LLOQ、低、中、高质量对照样品的日内、日间精密度(CV%)和准确度(RE%)均在15%以内。血浆和舌匀浆的平均提取回收率分别为50%和80%左右。该方法被成功地应用于OXP静脉给药后的药代动力学研究，以及一种新型口腔粘膜贴剂1h和4h后的舌组织分布。
Oxaliplatin (OXP), a third-generation platinum-based chemotherapy drug, was often indirectly analyzed via total platinum by an ICP-MS because it was difficult to directly quantify using an LC-MS/MS method, due to its instability, bad column separability and severe MS signal inhibition. Here, we developed and validated a specific, sensitive and reproducible LC-MS/MS method for the quantification of OXP itself in rat plasma and tongue tissue on a SCIEX 4000 QTRAP® MS/MS system equipped with a Phenomenex Lux 5u Cellulose-1 column (250 × 4.6 mm, 5 μm). This method was validated at the lower limit of detection (LOD) and the lower limit of quantitation (LLOQ) of 5 ng/mL and 10 ng/mL, with linearity of 10–5000 ng/mL (r2 > 0.99) and 10–2500 ng/mL (r2 > 0.99), in rat plasma and tongue homogenates, respectively. The intra- and inter-day precision (CV%) and accuracy (RE%) were within 15% for LLOQ, low-, medium- and high-quality control samples. The mean extraction recoveries were around 50% and 80% for plasma and tongue homogenates, respectively. This assay was successfully applied to pharmacokinetics study following intravenous administration of OXP, as well as tongue tissue distribution after 1 h and 4 h of a novel oral mucosal patch application.
登录
查看更多内容
影响因子：
3.7
作者：
Hanada, Kazuhiko;Suda, Makoto;Ogata, Hiroyasu
通讯作者：
Ogata, Hiroyasu
影响因子：
10.8
作者：
Donnelly, RF;McCarron, PA;Woolfson, AD
通讯作者：
Woolfson, AD
影响因子：
5.4
作者：
Gao X;Wu L;Tsai RYL;Ma J;Liu X;Chow DS;Liang D;Xie H
通讯作者：
Xie H
影响因子：
3.4
作者：
Falta, Thomas;Koellensperger, Gunda;Hann, Stephan
通讯作者：
Hann, Stephan
DOI：
10.1016/j.bbrc.2011.09.091
发表时间：
2011-10-22
影响因子：
3.1
作者：
Lin, Tao;Meng, Lingjun;Tsai, Robert Y. L.
通讯作者：
Tsai, Robert Y. L.