Short-cut route validated for monitoring fentanyl and its metabolite in urine using LC–MS/MS, in a wide concentration range

Abstract

Abstract Background Fentanyl is a highly potent analgesic, used in surgery, frequently abused or used in drug-facilitated crimes (DFC) and in military activities. It is also increasingly used in the treatment of chronic pain (especially in cancer patients). The improper use of transdermal patch forms can cause toxicity and deaths, related to overdose or combined use with other drug substances. Methods are needed for fast, reliable and inexpensive fentanyl detection and we aimed to develop such a method in urine using LC–MS/MS, especially for toxic and fatal concentrations which lack in the literature. Results An LC–MS/MS method has been presented for the co-determination of fentanyl and its main metabolite, norfentanyl in urine. The recoveries of the extraction method were 95(± 6)% and 70(± 9)% for fentanyl and norfentanyl, respectively. LOD and LOQ values are 1.7 and 14.0 ng/mL for fentanyl, while they were 20.6 ng/mL and 42.0 ng/mL for norfentanyl. Conclusion A rapid, sensitive, very practical, inexpensive and a high-recovery analysis method is developed and validated. This is the only fentanyl monitoring LC–MS/MS method in urine having a linearity over a wide range up to 500.0 ng/mL and its success is demonstrated on real samples in the therapeutic drug monitoring of fentanyl and is expected to contribute to clarify intoxications/deaths related to its use. Graphical Abstract

Keywords

• Extraction of fentanyl
• Fast LC–MS/MS analysis
• Validation in urine
• Wide linearity range
• Monitoring intoxication