Validated LC coupled to ESI-MS/MS analysis for fentanyl in human plasma and UV analysis in applied reservoir transdermal patches using a simple and rapid procedure

P>Background and objectives: Fentanyl has been used for cancer pain in transdermal formulation. The aim of the present study was to establish an analytical method for fentanyl in human plasma and in an applied transdermal reservoir patch (Reservoir-TTS), as well as for therapeutic monitoring of fentanyl in cancer patients. Method: Electro-spray ionization mass spectrometric (ESI-MS/MS) analysis followed solid phase extraction (SPE) from human plasma and drug reservoir extraction from an applied Reservoir-TTS. Each separation was completed within 9 min using an ODS column (particle size, 3 mu m, 2 center dot 0 mm i.d. x 75 mm) with 25% acetonitrile containing 5 mm ammonium acetate at pH 3 center dot 5. In the ESI-MS/MS analysis, the calibration curve for fentanyl was linear over a concentration range of 0 center dot 05-7 center dot 2 ng/mL in human plasma. The extraction efficiency of fentanyl in the human plasma was more than 95%. The intra- and interassay precision and accuracy were within 7% and 97 center dot 3-101 center dot 2%, respectively. The lower LOQ for fentanyl was 0 center dot 05 ng/mL in the human plasma. The extraction of the 25 mu g/h and 50 mu g/h Reservoir-TTS gave reproducible recoveries of 88 center dot 3% and 90 center dot 9%, respectively. The plasma concentration of fentanyl showed large interindividual variation in 31 patients with cancer pain. Conclusion: The method described is simple, accurate, and reproducible, and should be helpful for the therapeutic monitoring of fentanyl in cancer patients.