Determination of fentanyl in human plasma and fentanyl and norfentanyl in human urine using LC-MS/MS

被引:58
作者
Huynh, NH [1 ]
Tyrefors, N [1 ]
Ekman, L [1 ]
Johansson, M [1 ]
机构
[1] Quintiles AB, Analyt Serv, SE-75323 Uppsala, Sweden
关键词
fentanyl; norfentanyl; LC-MS/MS; plasma; urine; validation;
D O I
10.1016/j.jpba.2004.09.024
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
Fentanyl, a potent analgesic drug, has traditionally been used intravenously in surgical or diagnostic operations. Formulations with fentanyl in oral transmucosal delivery system and in transdermal depot-patch have also been developed against breakthrough pain in cancer patients. In this report, LC-MS/MS methods to determine fentanyl in human plasma as well as fentanyl and its main metabolite, norfentanyl, in human urine are presented together with validation data. The validation ranges were 0.020-10.0 and 0.100-50.0 ng/ml for fentanyl in plasma and urine, respectively, and 0.102-153 ng/ml for norfentanyl in urine. Liquid-liquid extraction of the compounds fentanyl, norfentanyl and the deuterated internal standards, fentanyl-d(5) and norfentanyl-d(5) from the matrixes was applied and separation was performed on a reversed phase YMC Pro C-18-column followed by MS/MS detection with electrospray in positive mode. The inter-assay precision (CV%) was better than 4.8% for fentanyl in plasma and 6.2% and 4.7% for fentanyl and norfentanyl, respectively, in urine. The ruggedness of the methods, selectivity, recovery, effect of dilution and long-term stability of the analytes in plasma and urine were investigated. Effect of haemolysis and stability of fentanyl in blood samples were also studied. The methods have been applied for the determination of fentanyl in plasma samples and fentanyl/norfentanyl in urine samples taken for pharmacokinetic evaluation after a single intra-venous (i.v.) dose of 75 mu g fentanyl. (c) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:1095 / 1100
页数:6
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