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目的建立并应用超高效液相色谱-串联质谱法(UPLC-MS/MS)测定人血浆中卡巴他赛与血浆蛋白的结合率。方法以拉洛他赛为内标,样品经叔丁基甲醚液液萃取,采用ACQUITY BEH C18色谱柱(50 mm×2.1 mm,1.7μm);流动相:2 mmol·L-1醋酸铵水溶液-乙腈;流速:0.2 mL·min-1;进样量:5μL;柱温:35℃;采用ESI正离子源,定量分析离子反应分别为m/z 836.36→m/z 555.26(卡巴他赛)和m/z 832.25→m/z 551.08(内标拉洛他赛)。结合平衡透析法,测定了卡巴他赛的人血浆蛋白结合率。结果卡巴他赛浓度在5~1 000 ng·mL-1范围内线性关系良好,定量下限为5 ng·mL-1,日内和日间精密度均小于15.0%,提取回收率为70.0%~91.4%,基质效应为87.4%~100.9%,可用于卡巴他赛的血浆蛋白结合率研究。卡巴他赛在低、中、高三个浓度下的人血浆蛋白结合率为(87.8±4.0)%、(76.4±0.8)%和(73.5±6.4)%。结论本方法简单、快速、灵敏,能满足分析要求。卡巴他赛与人血浆蛋白结合率较高,与血浆蛋白结合能力在考察的浓度范围内无浓度依赖性。
OBJECTIVE To establish and use UPLC-MS / MS to determine the ratio of cabazitaxel to plasma protein in human plasma. Methods Raloxabetol was used as the internal standard. The samples were extracted with tert-butyl methyl ether (TBS) using ACQUITY BEH C18 column (50 mm × 2.1 mm, 1.7 μm). The mobile phase consisted of 2 mmol·L -1 ammonium acetate in acetonitrile ; Flow rate: 0.2 mL · min-1; injection volume: 5 μL; column temperature: 35 ℃; ionization reaction using ESI positive ion source were m / z 836.36 → m / z 555.26 / z 832.25 → m / z 551.08 (internal standard loratadine). Combined with the equilibrium dialysis method, the plasma protein binding rate of cabazitaxel was determined. Results Cabazitaxel had a good linearity in the range of 5-1 000 ng · mL-1 with a lower limit of quantification of 5 ng · mL-1. The intra- and inter-day precision was less than 15.0% and the recovery was 70.0% -91.4 %, Matrix effect of 87.4% to 100.9%, can be used for plasma protein binding rate of cabazitaxel study. The plasma protein binding rates of cabazitaxel at low, medium and high concentrations were (87.8 ± 4.0)%, (76.4 ± 0.8)% and (73.5 ± 6.4)%, respectively. Conclusion This method is simple, fast and sensitive, and can meet the analytical requirements. Cabazitaxel has a high binding rate to human plasma proteins, and has no concentration-dependent plasma protein binding ability within the investigated concentration range.