背景和目的:吉西他滨已被用于治疗各种实体癌,包括,自1997年以来,转移性胰腺癌。这里,我们开发了HPLC-UV法测定血清吉西他滨水平,并将其用于药代动力学研究.材料和方法:分析是在反相柱上进行单个蛋白沉淀步骤后进行的,用磷酸钠缓冲液和甲醇等度洗脱。对于药代动力学研究,NOD/SCID小鼠通过皮下(SC)或腹膜内(IP)施用以100mg/kg接受单剂量的吉西他滨。在施用吉西他滨后5、15和30分钟以及1、2、4和6小时收集血样用于进一步分析。结果:分析的持续时间为~12.5分钟。校准曲线在1-400μM的范围内是线性的(r2=0.999)。GEM的平均回收率为96.53%,检测限为0.166μΜ。T1/2,Tmax,Cmax,AUC0-t,清除率为64.49分钟,5.00分钟,264.88μmol/L,9351.95μmol/L*min,0.0103(mg)/(μmol/L)/min,分别,SC管理。IP管理的相应值为59.34分钟,5.00分钟,300.73μmol/L,8981.35μmol/L*min和0.0108(mg)/(μmol/L)/min(与SC给药没有统计学差异)。结论:一个简单的,有效,敏感,已经开发了用于测量血清中吉西他滨的廉价方法。该方法可用于监测癌症患者的吉西他滨水平,作为治疗药物监测的一部分。
Background and Objectives:
Gemcitabine has been used to treat various solid cancers, including, since 1997, metastatic pancreatic cancer. Here, we developed an HPLC-UV method to determine serum
gemcitabine levels and use it in pharmacokinetic studies. Materials and Methods: The analysis was performed after a single protein precipitation step on a reversed-phase column, isocratically eluted with sodium phosphate buffer and methanol. For the pharmacokinetic study, NOD/SCID mice received a single dose of
gemcitabine at 100 mg/kg by either subcutaneous (SC) or intraperitoneal (IP) administration. Blood samples were collected at 5, 15, and 30 min and 1, 2, 4, and 6 h after the administration of gemcitabine for further analysis. Results: The duration of the analysis was ~12.5 min. The calibration curve was linear (r2 = 0.999) over the range of 1-400 μM. The mean recovery of GEM was 96.53% and the limit of detection was 0.166 μΜ. T1/2, Tmax, Cmax, AUC0-t, and clearance were 64.49 min, 5.00 min, 264.88 μmol/L, 9351.95 μmol/L*min, and 0.0103(mg)/(μmol/L)/min, respectively, for the SC administration. The corresponding values for the IP administration were 59.34 min, 5.00 min, 300.73 μmol/L, 8981.35 μmol/L*min and 0.0108(mg)/(μmol/L)/min (not statistically different from the SC administration). Conclusions: A simple, valid, sensitive, and inexpensive method for the measurement of
gemcitabine in serum has been developed. This method may be useful for monitoring
gemcitabine levels in cancer patients as part of therapeutic drug monitoring.