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气相色谱法测定微量尿液和血浆中的异环磷酰胺。

Gas chromatographic determination of ifosfamide in microvolumes of urine and plasma.

作者信息

Kaijser G P, Beijnen J H, Bult A, Wiese G, de Kraker J, Underberg W J

机构信息

Department of Pharmaceutical Analysis, Faculty of Pharmacy, Utrecht University, Netherlands.

出版信息

J Chromatogr. 1991 Nov 15;571(1-2):121-31. doi: 10.1016/0378-4347(91)80439-j.

Abstract

In oncology, particularly in pediatric malignancies, high doses (5-10 g/m2) of the oxazaphosphorine ifosfamide play an important role in the treatment of sarcomas. Pharmacokinetic data of ifosfamide and its metabolites in these cases are scanty. Considering the special demands of the determination of ifosfamide in plasma of young children, a very sensitive capillary gas chromatographic method, requiring only 50 microliters of plasma, has been developed. This bioanalysis of ifosfamide shows good linearity and accuracy in the concentration range 10 ng to 100 micrograms per ml of plasma and 25 ng to 1 mg per ml of urine. The absolute limits of detection in plasma and urine are 2 ng/ml and 5 ng/ml, respectively. The stability of various solutions of ifosfamide and trofosfamide was tested and proved to be satisfactory, except for ifosfamide in plasma and urine kept in the refrigerator. The validity of the method for pharmacokinetic purposes is shown in the case of one patient.

摘要

在肿瘤学领域,尤其是在儿童恶性肿瘤中,高剂量(5 - 10 g/m²)的氮杂磷酰胺异环磷酰胺在肉瘤治疗中发挥着重要作用。在这些情况下,异环磷酰胺及其代谢物的药代动力学数据很少。考虑到测定幼儿血浆中异环磷酰胺的特殊要求,已开发出一种非常灵敏的毛细管气相色谱法,该方法仅需50微升血浆。这种异环磷酰胺的生物分析在每毫升血浆10纳克至100微克以及每毫升尿液25纳克至1毫克的浓度范围内显示出良好的线性和准确性。血浆和尿液中的绝对检测限分别为2纳克/毫升和5纳克/毫升。除了保存在冰箱中的血浆和尿液中的异环磷酰胺外,对异环磷酰胺和曲磷胺的各种溶液的稳定性进行了测试,结果证明是令人满意的。该方法在药代动力学方面的有效性在一名患者的案例中得到了体现。

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