A hybrid approach to urine drug testing using high-resolution mass spectrometry and select immunoassays.

OBJECTIVES: The major objective of this research was to propose a simplified approach for the evaluation of medication adherence in chronic pain management patients, using liquid chromatography time-of-flight (TOF) mass spectrometry, performed in parallel with select homogeneous enzyme immunoassays (HEIAs). We called it a "hybrid" approach to urine drug testing. METHODS: The hybrid approach was defined based on anticipated positivity rates, availability of commercial reagents for HEIAs, and assay performance, particularly analytical sensitivity and specificity for drug(s) of interest. Subsequent to implementation of the hybrid approach, time to result was compared with that observed with other urine drug testing approaches. RESULTS: Opioids, benzodiazepines, zolpidem, amphetamine-like stimulants, and methylphenidate metabolite were detected by TOF mass spectrometry to maximize specificity and sensitivity of these 37 drug analytes. Barbiturates, cannabinoid metabolite, carisoprodol, cocaine metabolite, ethyl glucuronide, methadone, phencyclidine, propoxyphene, and tramadol were detected by HEIAs that performed adequately and/or for which positivity rates were very low. Time to result was significantly reduced compared with the traditional approach. CONCLUSIONS: The hybrid approach to urine drug testing provides a simplified and analytically specific testing process that minimizes the need for secondary confirmation.

Rapid screening for 67 drugs and metabolites in serum or plasma by accurate-mass LC-TOF-MS.

Sixty-seven drugs and metabolites were detected in serum or plasma using a fast (7.5 min) liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS) method. This method was developed as a blood drug screen, with emphasis on the detection of common drugs of abuse and drugs used to manage chronic pain. Qualitative drug detection may identify a drug exposure, assure patient adherence with prescribed therapy and document abstinence from non-prescribed medications. Compound identification is based on chromatographic retention time, mass, isotope spacing and isotope abundance. Data analysis software (Agilent) generates a compound score based on how well these observed criteria matched theoretical and empirical values. The method was validated using fortified samples and 299 residual patient specimens (920 positive results). All results were confirmed by gas chromatography-MS or LC-tandem MS. The accuracy of positive results (samples meeting all qualitative criteria for retention time, mass and compound score) was >90% for drugs and/or metabolites, except for two benzodiazepines. There were 35 false positive results (seven compounds, 3.8%) that could be distinguished by retention time and/or absence of metabolites. The most frequent was 6-acetylmorphine in the absence of morphine. The LC-TOF-MS targeted screening method presented represents a sensitive and specific technology for drug screening of serum or plasma.