Robust differentiation of isobaric urine opioids and n-desmethyl metabolites using LC-hybrid tandem Mass spectrometry (LC-MSMS) and automated library search.

摘要

1) Norcodeine (NorCDN) and hydromorphone (HDMN) may co-elute with LC conditions typically used for opioid identification. 2) We observed NorCDN present at concentrations sufficient to yield an apparent HDMN > 5 ng/mL cutoff when NorCDN is integrated as HDMN (using the HDMN SRM 3) Qualifier SRM ratios for NorCDN can be within range (+/-20percent of calibrator) for HDMN - yielding a false qualitative identification as HDMN. 4) Therefore - a false positive HDMN may occur following codeine exposure when norcodeine concentrations are approx>100 ng/mL. 5) LC-MSMS methods for HDMN should be evaluated for NorCDN interference using appropriately high NorCDN concentrations. 6) HDMN can reliably be distinguished from NorCDN using full scan spectra (SRM-IDA-EPI acquisition) at high CES (60+/-25). 7) We observed free normetabolites in some samples at concentrations that are as high or higher than the free parent drug or free o-desmethylmetabolite. 8) When multiple opioids/o-desmethylmetabolites are present - measurement of normetabolites might prove useful to identify source drugs. 9) Further investigation with controlled polypharmacy dosing is needed.