采用带荧光检测的高效液相色谱法对长春曲醇的代谢物N-（去乙酰基-O-4-长春碱酰基-23）-L-色氨酸进行生物测定。

Biodetermination of N-(deacetyl-O-4-vinblastoyl-23)-L-tryptophan, a metabolite of vintriptol, by high-performance liquid chromatography with fluorescence detection.

作者信息

van Tellingen O, Beijnen J H, Baurain R, ten Bokkel Huinink W W, van der Woude H R, Nooyen W J

机构信息

Department of Clinical Chemistry, Netherlands Cancer Institute, Amsterdam.

出版信息

J Chromatogr. 1992 Feb 14;574(2):293-8. doi: 10.1016/0378-4347(92)80042-o.

DOI:10.1016/0378-4347(92)80042-o

PMID:1618962

Abstract

The determination of N-(deacetyl-O-4-vinblastoyl-23)-L-tryptophan (vintriptol acid, VtrpA), a metabolite of the investigational semi-synthetic vinca alkaloid vintriptol [N-(deacetyl-O-4-vinblastoyl-23)-L-ethyltryptophan, VtrpE], in plasma and urine samples is described. Sample pretreatment included liquid-liquid extraction of the buffered (pH 5.0) biological samples with chloroform-2-propanol (95:5, v/v). The analyses were performed by ion-exchange high-performance liquid chromatography on normal-phase silica with fluorescence detection. The assay was applied to the analysis of samples from cancer patients who had been treated with VtrpE in a phase I clinical study. VtrpA was found to be a principal metabolite of VtrpE with up to 1.2% of the administered dose excreted in the urine.

摘要

本文描述了对血浆和尿液样本中N-(去乙酰基-O-4-长春瑞滨酰基-23)-L-色氨酸（长春瑞滨酸，VtrpA）的测定，长春瑞滨酸是研究中的半合成长春花生物碱长春瑞滨 [N-(去乙酰基-O-4-长春瑞滨酰基-23)-L-乙基色氨酸，VtrpE] 的一种代谢产物。样品预处理包括用氯仿 - 2 - 丙醇（95:5，v/v）对缓冲（pH 5.0）的生物样品进行液 - 液萃取。分析采用离子交换高效液相色谱法，在正相硅胶上进行荧光检测。该测定法应用于在一项I期临床研究中接受VtrpE治疗的癌症患者样本的分析。发现VtrpA是VtrpE的主要代谢产物，尿液中排泄的剂量高达给药剂量的1.2%。