Determination of fentanyl, metabolite and analogs in urine by GC/MS

Abstract

A rapid and sensitive method for the simultaneous determination of alfentanyl, sufentanyl and fentanyl (and its major metabolite norfentanyl) in urine was developed and validated. The method involved a liquid-liquid extraction in alkaline conditions, derivatization with pentafluoropropionic anhydride to improve the sensitivity for norfentanyl and subsequent analysis in GC/MS. The LODs are 0.08 ng ml(-1) for all substances (0.04 ng ml(-1) for alfentanyl). Intra- and inter-day precision coefficient of variation was always below 15%; mean relative error (accuracy) was always below 15%. The method was linear for all analytes, with quadratic regression of calibration curves always higher than 0.99. The method was applied to real samples of subjects who had received therapeutic doses of fentanyl, showing its suitability for the determination of low levels of these substances. The method was also applied to a subject whose death was attributed to fentanyl overdose.

Comparison of two automated solid phase extractions for the detection of ten fentanyl analogs and metabolites in human urine using liquid chromatography tandem mass spectrometry

“…These quality control levels were selected based on their correlation to anticipated exposure levels in those exposed to non-fatal therapeutic doses, which have been reported to be in the range of 0.8-4.0 ng/mL for fentanyl in urine [7]. Calibrators were prepared in pooled urine and were extracted and analyzed with the quality control samples over the course of two months.…”

“…Thus, symptomology alone cannot be used to differentiate among exposure to different opioids; therefore, a selective analytical method is needed to distinguish fentanyl exposure from other opioids. The high potency of fentanyls, 50-100 times more potent than morphine, along with the low renal clearance of fentanyl analogs, results in low concentrations (0.8 ng/mL-4 ng/mL) of the intact fentanyl excreted via urine following therapeutic doses [7]. The biological half-life of fentanyl is 1-3.5 hours [8]; however, the nor-metabolite, the oxidative n-dealkylation at the piperdine nitrogen of the parent compound, has been detected at concentrations of 0.3 to 0.7 ng/mL up to 96 hours following therapeutic doses [9].…”

Laboratory Testing for Prescription Opioids

“…Although not routinely applied in many standard urine drug-testing panels, fentanyl-specific immunoassays have been developed [27,61,62]. A number of other analytical methods including gas chromatography-mass spectroscopy (GC-MS) [63][64][65][66] and LC-MS have also been described [67][68][69][70]. Some of these methods also include detection of fentanyl-like compounds in addition to fentanyl [32].…”

Analysis of fentanyl derivatives by ultra high performance liquid chromatography with diode array ultraviolet and single quadrupole mass spectrometric detection

“…Separation techniques are excellent complements to detection techniques such as MS. GC-MS [10,11,[14][15][16][17][18][19], and LC-MS [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]are the most commonly employed techniques in the analysis of fentanyls. CE-MS [35] has also been used to separate and analyze fentanyl derivatives and analogues.…”