Validated GC-MS analysis for the determination of residual fentanyl in applied Durogesic reservoir and Durogesic D-Trans matrix transdermal fentanyl patches.

The method development and validation characteristics are described of a simple gas chromatographic-mass spectrometric (GC-MS) analytical procedure to determine residual fentanyl in used Durogesic reservoir patches and Durogesic D-Trans matrix technology based systems to estimate the actual rate of transdermal fentanyl delivered in individual patients. The sample preparation protocol constituting a saline based extraction of sets of new patches of each nominal dose available, resulted in fentanyl extraction recoveries to increase steadily as a function of increasing extraction time. For the reservoir type transdermal therapeutic system (TTS), fentanyl extraction efficiencies at equilibrium (16 h) ranged from approximately 60% (100-microg/h TTS) to 95% (25-microg/h TTS), whereas for the matrix type system considerable lower recoveries were demonstrated for the highest nominal dose rates (35%-52%), while reaching 90% for the 25-microg/h system. For the latter type of fentanyl TTS, an optimized methanol based extraction protocol yielded virtually quantitative fentanyl recoveries for each matrix patch nominal dose level at substantially shorter extraction periods (15 min). The GC-MS analytical method using selected ion monitoring (SIM) and deuterated fentanyl as internal standard was shown to be adequately selective with regard to the presence of other compounds in the Durogesic patches. It was further demonstrated that the developed analytical protocols provided highly reproducible and accurate estimates of the initial fentanyl content of each patch type at all available nominal doses, with coefficients of variation and relative errors generally below 10%. These advantageous assay validation characteristics can be further transposed to the application of residual fentanyl level estimates in used patches, provided that with each batch of samples also a set of new TTSs with equal dose is assayed to perfectly mimic extraction phenomena. Finally, the presented GC-MS analytical protocol was successfully applied for the determination of residual fentanyl in a subset of 57 reservoir type patches obtained from four palliative patients.