Katrin Lachenmeier

Determination of opioid analgesics in hair samples using liquid chromatography/tandem mass spectrometry and application to patients under palliative care.

Hair testing procedures allow a cumulative reflection of long-term drug abuse and are useful as a test for compliance in clinical toxicology. In the present study, liquid chromatography coupled with tandem mass spectrometry was used to determine analgesic opioid drugs in hair samples. The procedure used a simple methanolic extraction, and the evaporated extract was analyzed directly. A selective and sensitive procedure for the simultaneous determination of bisnortilidine, nortilidine, tilidine, buprenorphine, codeine, oxycodone, fentanyl, norfentanyl, hydromorphone, morphine, normorphine, oxymorphone, methadone, piritramide, and tramadol was developed and fully validated. The method fulfilled validation criteria and was shown to be sensitive, with limits of detection ranging from 0.008 to 0.017 ng/mg hair matrix, and precision ranging between 3.1% and 14.9 %. The applicability of the method was shown by analysis of authentic hair samples from patients receiving opioids for the treatment of cancer pain (eg, fentanyl was detected in concentrations up to 0.292 ng/mg, tramadol in concentrations up to 0.612 ng/mg of hair of 1 patient). Hair analysis was shown to be a complementary and useful tool in monitoring the drug-taking behavior of patients consuming opioid analgesics for the treatment of pain. In self-reports and medical records especially, the ingestion of tramadol and methadone was found to be dramatically underreported. In summary, hair analyses gave important additional information for the medical treatment of patients, the results often coming as a surprise to even the attending physicians.

Dose-Concentration Relationships of Methadone and EDDP in Hair of Patients on a Methadone-Maintenance Program

After controlled oral administration of d,l-methadone solution (15–260 mg/day) in the context of a methadone-maintenance program, concentrations of methadone and 2-ethylidine-1,5-dimethyl-3,3-diphenyl-l-pyrrolidine (EDDP), in head hair were determined (N=41), using a fully automated headspace solid-phase microextraction procedure in combination with gas chromatography and mass spectrometry (HS-SPME/GC/MS).Methadone was present in all samples in concentrations ranging from 0.25 to 13.29 ng/mg (mean 2.69±0.45 ng/mg). EDDP was also present in every sample in concentrations ranging from 0.05 to 2.17 ng/mg (mean 0.43±0.08). The concentration ratio methadone/EDDP was 7.5±5.7 in the proximal segments, but decreased to 4.8±1.4 in the distal segments. A statistically significant correlation between the intake dose and the methadone and EDDP concentrations in the subjects’ hair could be established only in the proximal segments (r=0.913 for methadone and r=0.901 for EDDP), but not in the distal segments. In all, 131 segments analyzed, the correlation coefficient was r=0.760 for methadone and r=0.738 for EDDP. In comparison to the dose-concentration relationship reported in the literature, we found a better correlation with higher correlation coefficients especially in the proximal segments.However, owing to a broad distribution in the correlation between dosage and concentration, the determination of methadone and EDDP in hair holds only limited information about prior methadone administration.