ent-dextilidine and norfentanyl

Narcotic analgesics are widely (ab) used and sometimes only occur in low concentrations in biological samples. Therefore, a highly sensitive liquid chromatography tandem mass spectrometry method was developed for simultaneous analysis of 9 narcotic analgesics and metabolites (buprenorphine, O-desmethyltramadol, fentanyl, norbuprenorphine, norfentanyl, pethidine, piritramide, tilidine and tramadol) in urine and whole blood. Sample preparation was performed on a mixed-mode cation exchange solid phase extraction cartridge with an additional alkaline wash step to decrease matrix effects and thus increase sensitivity. Ionization with electrospray ionization was found to be more efficient than atmospheric pressure chemical ionization. The use of a mobile phase of high pH resulted in higher electrospray ionization signals than the conventional low pH mobile phases. In the final method, gradient elution with 10mM ammonium bicarbonate (pH 9) and methanol was performed on a small particle column (Acquity C18, 1.7 μm, 2.1 mm × 50 mm). Selectivity, matrix effects, recovery, linearity, sensitivity, precision, accuracy and stability were validated in urine and whole blood. All parameters were successfully evaluated and the method showed very high sensitivity, which was the major aim of this study. The applicability of the method was demonstrated by analysis of several forensic cases involving narcotic analgesics.

Topics: Analgesics, Opioid; Analysis of Variance; Buprenorphine; Chromatography, Liquid; Fentanyl; Forensic Toxicology; Humans; Meperidine; Pirinitramide; Regression Analysis; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Tilidine; Tramadol

A fully validated liquid chromatographic procedure coupled with electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) is presented for quantitative determination of the opioids buprenorphine, codeine, fentanyl, hydromorphone, methadone, morphine, oxycodone, oxymorphone, piritramide, tilidine, and tramadol together with their metabolites bisnortilidine, morphine-glucuronides, norfentanyl, and nortilidine in blood plasma after an automatically performed solid-phase extraction (SPE). Separation was achieved in 35 min on a Phenomenex C12 MAX-RP column (4 microm, 150 x 2 mm) using a gradient of ammonium formiate buffer (pH 3.5) and acetonitrile. The validation data were within the required limits. The assay was successfully applied to authentic plasma samples, allowing confirmation of the diagnosis of overdose situations as well as monitoring of patients' compliance, especially in patients under palliative care.

Topics: Analgesics, Opioid; Chromatography, Liquid; Fentanyl; Humans; Morphine Derivatives; Palliative Care; Patient Compliance; Spectrometry, Mass, Electrospray Ionization; Tilidine