Department of Clinical Pharmacology, Slotervaart Hospital, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
J Chromatogr B Analyt Technol Biomed Life Sci. 2011 May 1;879(15-16):1149-55. doi: 10.1016/j.jchromb.2011.03.021. Epub 2011 Mar 17.
This paper presents specific and sensitive high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) assays for the quantification of the novel anticancer agent eribulin in human plasma, whole blood, urine and faeces. These assays, developed to support clinical pharmacological studies with the drug, quantify eribulin concentration ranges of 0.2-100ng/mL for plasma, 0.5-100 ng/mL for whole blood and urine and 0.1-25 μg/g for faeces, using sample volumes of 500 μL or 250 μg (faeces). Samples were prepared with liquid-liquid extraction, separated on a C18 column with gradient elution and analysed with a triple quadrupole MS, in positive ion mode. A structural analogue of eribulin was used as internal standard for the quantification. The assays were linear with correlation coefficients (r(2)) of 0.99 and better, whereby the deviation from nominal concentrations ranged from -8.2 to 8.9% with CV values of maximally 14.2%. Stability assessments demonstrated that eribulin is stable at -20°C in plasma, whole blood, urine and faeces for at least 38, 4, 10.5 and 5 months, respectively. In conclusion, the validation results show that the assays are specific and accurate and can therefore adequately be applied to support clinical studies of eribulin.
本文介绍了一种专用于定量检测新型抗癌药物艾立布林的高效液相色谱-串联质谱法（HPLC-MS/MS）检测方法，该方法可用于人血浆、全血、尿液和粪便样本。这些检测方法是为支持该药物的临床药理学研究而开发的，可定量检测血浆中艾立布林浓度范围为 0.2-100ng/mL，全血和尿液中为 0.5-100ng/mL，粪便中为 0.1-25μg/g，所用样本量为 500μL 或 250μg（粪便）。样品经液液萃取处理，在 C18 柱上以梯度洗脱方式分离，采用三重四极杆质谱仪，正离子模式检测。艾立布林的结构类似物被用作定量的内标。检测方法呈线性，相关系数（r(2)）大于 0.99，偏差均在-8.2%至 8.9%之间，变异系数（CV）最大为 14.2%。稳定性评估表明，艾立布林在 -20°C 下于血浆、全血、尿液和粪便中至少稳定 38、4、10.5 和 5 个月。总之，验证结果表明该检测方法具有特异性和准确性，因此可以充分应用于支持艾立布林的临床研究。
