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首页> 外文期刊>Journal of mass spectrometry: JMS >Simultaneous determination of gemcitabine and its main metabolite, dFdU, in plasma of patients with advanced non-small-cell lung cancer by high-performance liquid chromatography-tandem mass spectrometry
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Simultaneous determination of gemcitabine and its main metabolite, dFdU, in plasma of patients with advanced non-small-cell lung cancer by high-performance liquid chromatography-tandem mass spectrometry

机译：高效液相色谱-串联质谱法同时测定晚期非小细胞肺癌患者血浆中的吉西他滨及其主要代谢产物dFdU

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Gemcitabine, 2',2'-difluoro-2'-deoxycytidine (dFdC) is a pyrimidine antimetabolite employed against several human malignancies. It undergoes intracellular activation to the pharmacologically active triphosphate form (dFdCTP) and metabolic inactivation to the metabolite 2',2'-difluorodeoxyuridine (dFdU). In order to investigate the human plasma pharmacokinetics of dFdC and dFdU, we developed and validated an HPLC-MS/MS method, adding 2'-deoxycytidine as internal standard and simply precipitating the protein with acetonitrile. The method requires a small sample (125 mu l), and it is rapid and selective, allowing good resolution of peaks from the plasma matrix in only 7 min. It is sensitive, precise and accurate, with overall precision, expressed as CV%, always less than 10.0% for both analytes and high recovery: >80%. The limits of detection for dFdC and dFdU were 0.1 and 1.1 ng/ml, but considering the high concentrations in the plasma of patients investigated, we set the limit of quantitation at 20 ng/ml (0.08 mu M) for c1FdC and 250 ng/ml for dFdU, and validated the assay up to the dFdC concentration of 6.0 mu g/ml (22.8 mu M). The method was successfully used to study the drug pharmacokinetics in patients with advanced non-small-cell lung cancer in a phase II trial with gemcitabine administered as a fixed dose-rate infusion.
机译：吉西他滨2'，2'-二氟-2'-脱氧胞苷（dFdC）是一种嘧啶抗代谢物，可用于治疗多种人类恶性肿瘤。它经历细胞内活化为药理学活性的三磷酸形式（dFdCTP）和代谢失活为代谢物2'，2'-二氟脱氧尿苷（dFdU）。为了研究dFdC和dFdU在人血浆中的药代动力学，我们开发并验证了HPLC-MS / MS方法，添加2'-脱氧胞苷作为内标，并简单地用乙腈沉淀蛋白质。该方法需要少量样品（125μl），并且快速，选择性好，仅需7分钟即可从血浆基质中分离出良好的峰。它灵敏，精确，准确，总体精度以CV％表示，对于分析物而言始终小于10.0％，回收率高：> 80％。 dFdC和dFdU的检出限分别为0.1和1.1 ng / ml，但考虑到所研究患者血浆中的高浓度，我们将c1FdC和250 ng / ml的定量限设定为20 ng / ml（0.08μM）。毫升的dFdU，并验证了dFdC浓度高达6.0μg / ml（22.8μM）的测定。该方法已成功用于吉西他滨固定剂量率输注的II期临床研究中，用于晚期非小细胞肺癌患者的药物药代动力学。

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