Rapid determination of gemcitabine in plasma and serum using reversed-phase HPLC

被引:35
|
作者
Lanz, Christian
Frueh, Martin
Thormann, Wolfgang
Cerny, Thomas
Lauterburg, Bernhard H.
机构
[1] Univ Bern, Dept Clin Pharmacol, CH-3010 Bern, Switzerland
[2] Kantonsspital, Dept Innere Med, Fachbereich Onkol Hamatol, St Gallen, Switzerland
关键词
2'-deoxy-2'; 2'-difluorouridine; gemcitabine; high-performance liquid chromatography; intravenous; oral; subcutaneous;
D O I
10.1002/jssc.200600534
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
Gemcitabine (2'2'-difluorodeoxycytidine) is a pyrimidine analog used in the treatment of a variety of solid tumors. After intravenous (i.v.) administration, it is rapidly inactivated to 2'-deoxy-2',2'-difluorouridine (dFdU). A sensitive analytical method for the quantitation of gemcitabine is required for the assessment of alternative dosage and treatment schemes. A rapid and robust RP-HPLC assay for analysis of gemcitabine in human and animal plasma and serum was developed and validated using 2'-deoxyuridine (dU) and 5-fluoro-2'-deoxyuridine (5FdU) as internal standards. It is based on protein precipitation, the use of an Atlantis dC18 column of 100 mm length (inner diameter, 4.6 mm; particle size, 3 mu m) and isocratic elution using a 10 mM phosphate buffer, pH 3.0, followed by isocratic elution with the same buffer containing 3% of ACN. For gemcitabine, RSD values for intraday and interday precision were < 4.4 and 5.3%, respectively, the LOQ was 20 ng/mL, and the assay was linear in the range of 0.020-20 mu g/mL with an accuracy of >= 89%. The recovery for gemcitabine, dU and 5FdU was 86-98%. The assay was applied to determine gemcitabine levels in plasma samples of patients collected during and shortly after conventional infusion of 25-30 mg/kg body mass (levels: 2.0-18.9 mu g/ml,) and rats that received lower doses (1.5 mg/kg) via i.v., subcutaneous and oral drug administration (levels: 0.20-2.60 mu g/mL). It could also be applied to estimate dFdU levels in human plasma.
引用
收藏
页码:1811 / 1820
页数:10
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