采用电子捕获检测法的灵敏熔融石英毛细管气相色谱法测定绵羊胎液中的吲哚美辛。

Sensitive fused-silica capillary gas chromatographic assay using electron-capture detection for indomethacin in ovine fetal fluids.

作者信息

Krishna R, Riggs K W, Walker M P, Kwan E, Rurak D W

机构信息

Division of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.

出版信息

J Chromatogr B Biomed Appl. 1995 Dec 1;674(1):65-75. doi: 10.1016/0378-4347(95)00291-x.

DOI:10.1016/0378-4347(95)00291-x

PMID:8749253

Abstract

A sensitive gas chromatographic (GC) method with electron-capture detection (ECD) has been developed to quantitate indomethacin (IND) in plasma, urine, amniotic, and tracheal fluids obtained from the pregnant sheep model. IND and the internal standard, alpha-methylindomethacin (alpha-Me-IND) are extracted by a simple liquid-liquid extraction procedure using ethyl acetate and derivatized with N-methyl-N-(tert.-butyldimethyl-silyl)trifluoroacetamide (MTBSTFA) at 60 degrees C for 50 min. The limit of quantitation (LOQ) is 1 ng/ml with a C.V. < 10% and signal-to-noise ratio > 10. Recoveries from all fluids were greater than 80%. Calibration curves were linear over the range of 1-32 ng/ml with a coefficient of determination (r2) > 0.999. Inter- and intra-day coefficients of variation were < 10% at concentrations of 2-32 ng/ml, and < 20% at the LOQ. Applicability of the developed method is demonstrated for a pharmacokinetic study of IND samples collected following long-term infusion of IND in a chronically instrumented ovine fetus.

摘要

已开发出一种采用电子捕获检测（ECD）的灵敏气相色谱（GC）方法，用于定量测定从妊娠绵羊模型获得的血浆、尿液、羊水和气管液中的吲哚美辛（IND）。IND和内标α-甲基吲哚美辛（α-Me-IND）通过使用乙酸乙酯的简单液-液萃取程序进行萃取，并在60℃下用N-甲基-N-（叔丁基二甲基甲硅烷基）三氟乙酰胺（MTBSTFA）衍生化50分钟。定量限（LOQ）为1 ng/ml，变异系数（C.V.）<10%，信噪比>10。所有液体的回收率均大于80%。校准曲线在1-32 ng/ml范围内呈线性，决定系数（r2）>0.999。在2-32 ng/ml的浓度下，日间和日内变异系数<10%，在定量限处<20%。所开发方法的适用性在对长期输注IND的慢性植入仪器的绵羊胎儿采集的IND样品进行的药代动力学研究中得到了证明。