High-throughput HPLC-MS/MS method to determine ibandronate in human plasma for pharmacokinetic applications
High-throughput HPLC-MS/MS method to determine ibandronate in human plasma for pharmacokinetic applications
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DOI：
10.1016/j.jchromb.2009.08.007
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发表时间：
2009-10-01
影响因子：
3
通讯作者：
Tudoroniu, Ariana
中科院分区：
文献类型：
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作者：
Tarcomnicu, Isabela;Gheorghe, Mihaela Cristina;Tudoroniu, Ariana
开发了一种灵敏的高通量液相色谱-串联质谱 (LC-MS/MS) 方法，用于定量人血浆中的伊班膦酸盐。在之前的一项研究中，我们使用衍生化方法分析了接受治疗剂量治疗的受试者尿液样本中的阿仑膦酸钠；采用并改进了类似的衍生化方法来测定血浆中的伊班膦酸盐。通过液-液萃取从生物基质中分离出双膦酸盐，并用三甲基甲硅烷基重氮甲烷衍生化，然后在反相柱（Supelco Discovery HSC18）上分离并在四极线性离子阱质谱仪（API 4000 QTrap）上检测。对萃取和衍生化的各种参数进行了优化，以获得足够的回收率、高衍生化产率和最小的离子抑制：使用氘代类似物 d3-伊班膦酸盐作为内标。获得转变 376.1 -> 114.2 和 379.1 -> 61.0 分别用于监测伊班膦酸盐和 d3-伊班膦酸盐衍生物。多重液相色谱系统使两次色谱运行的重叠成为可能，因此进样间隔缩短至仅 2 分钟，对于此类化合物来说，这是非常短的分析时间。该方法在 0.2-175.0 ng/ml 的定量范围内得到充分验证，可以对治疗剂量下预期的伊班膦酸盐血浆浓度进行适当评估，这一点已通过药代动力学研究的应用得到证实。在选定范围内具有良好的线性度 (r > 0.99)，准确度和精密度在目标值的 +/- 15% 范围内，并且回收率超过 50%。 (C) 2009 Elsevier B.V. 保留所有权利。
A sensitive high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of ibandronate in human plasma. In a previous study, we have analyzed alendronate in urine samples of subjects treated at therapeutic dosages, using a derivatization approach; a similar derivatization was adapted and improved to determine ibandronate in plasma. The bisphosphonate was isolated from the biological matrix by liquid-liquid extraction, and derivatized with trimethylsilyldiazomethane prior to separation on a reversed-phase column (Supelco Discovery HSC18) and detection on a quadrupole-linear ion trap mass spectrometer (API 4000 QTrap). Various parameters of extraction and derivatization were optimized in order to get adequate recovery, high derivatization yield and minimal ion suppression: a deuterated analogue, d3-ibandronate, was used as internal standard. The transitions 376.1 -> 114.2 and 379.1 -> 61.0 were acquired to monitor ibandronate and d3-ibandronate derivatives, respectively. A multiplexing LC system made possible the overlapping of two chromatographic runs, thus the interval between injections being reduced to only 2 min, a very short analysis time for compounds of this class. The method was fully validated over the quantification range 0.2-175.0 ng/ml, allowing an appropriate evaluation of the plasma concentrations of ibandronate, expected at therapeutic dosage, as proved by application to a pharmacokinetic study. A good linearity over the selected range (r > 0.99), accuracy and precision within +/- 15% of the target values and a recovery over 50% were obtained. (C) 2009 Elsevier B.V. All rights reserved.