A comprehensive LC-MS-based quantitative analysis of fentanyl-like drugs in plasma and urine

Fentanyl, norfentanyl, alfentanil, sufentanil, remifentanil and 3-methylfentanyl are potent, short-acting, synthetic narcotic analgesics that are not revealed in standard opiate immunoassays. In this article, a fully validated analytical method for the determination of these fentanyl-type compounds in plasma and urine is presented, consisting of a liquid-liquid extraction followed by a LC-MS/MS analysis using electrospray ionisation in the positive ionisation mode. Fentanyl-d(5) and norfentanyl-d(5) were used as internal standards. The lower LOQ in plasma and urine was 0.1 ng/mL for fentanyl, norfentanyl, alfentanil, remifentanil and 3-methylfentanyl, and 0.2 ng/mL for sufentanil. The method proved linear over a concentration range of 0.2-50 ng/mL for sufentanil and 0.1-50 ng/mL for all other analytes, with correlation coefficients of 0.998 or better. The analytical procedure showed excellent selectivity and precision (all CVs below 15%) for all analytes. Accuracy was good, except for sufentanil, where deviations of more than 15% from nominal concentrations were observed. No matrix effects were observed, and stability of stock and internal standard solutions was within acceptability limits.