Determination of morphine and oxymorphone in exhaled breath condensate samples: Application of microwave enhanced three-component deep eutectic solvent-based air-assisted liquid-liquid microextraction and derivatization prior to gas chromatography-mass spectrometry.

In this work, a microwave-enhanced air-assisted liquid-liquid microextraction method combined with gas chromatography-mass spectrometry has been developed for morphine and oxymorphone assessment in EBC samples. For this purpose, choline chloride-menthol-phenylacetic acid deep eutectic solvent (as an extraction solvent), butyl chloroformate (as a derivatization agent), and picoline (as a catalyst) are used. After performing predetermined extraction cycles in the microextraction method, the obtained cloudy solution is exposed to microwave irradiations to enhance extraction and derivatization efficiencies. The method provided low limits of detection (morphine 2.1 and oxymorphone 1.5 ng mL-1) and quantification (morphine 7.2 and oxymorphone 5.2 ng mL-1) in the EBC samples. The method had proper repeatability, accuracy, and stability expressed as relative standard deviations less than 5.1, 9, and 9%, respectively. The developed method was successfully used to determine morphine and oxymorphone concentrations in the EBC samples of addict patients.

Positivity rates of drugs in patients treated for opioid dependence with buprenorphine: A comparison of oral fluid and urine using paired collections and LC-MS/MS.

BACKGROUND: Drug testing is recommended as part of comprehensive monitoring for medication-assisted treatment. Alternative matrices including oral fluid offer a number of advantages when compared with conventional urine testing but are not as well characterized. This study aims to compare positivity rates of drugs and drug classes in oral fluid and urine as a measure of the clinical utility of oral fluid in the evaluation and treatment of patients with opioid use disorders. METHODS: A retrospective review of paired oral fluid and urine test results from Millennium Health's laboratory database was performed for 2746 patients with reported prescriptions for buprenorphine products used in the treatment of opioid dependence. Specimens were tested using quantitative LC-MS/MS for 34 medications, metabolites and illicit drugs. RESULTS: A number of medications and illicit drugs were detected at comparable or higher rates in oral fluid vs. urine such as cocaine (15.7% vs. 7.9%), opiates (13.4% vs. 10.0%), oxycodone (8.6% vs. 3.7%), hydrocodone (3.0% vs. 1.2%) and others. Lower detection rates were observed in oral fluid vs. urine for benzodiazepines (6.6% vs. 8.7%), cannabinoids (15.5% vs. 19.5%), oxymorphone (1.8% vs. 3.1%) and hydromorphone (0.8% vs. 4.5%). CONCLUSIONS: Clinicians may find oral fluid advantageous for detection of specific drugs and medications in certain clinical situations. Understanding the relative differences between urine and oral fluid can help clinicians carefully select tests best suited for detection in their respective matrix. To our knowledge, this is the largest inter-matrix patient comparison study using paired collections and direct to definitive testing.

Development of a Quantitative LC-MS-MS Assay for Codeine, Morphine, 6-Acetylmorphine, Hydrocodone, Hydromorphone, Oxycodone and Oxymorphone in Neat Oral Fluid.

Recent advances in analytical capabilities allowing for the identification and quantification of drugs and metabolites in small volumes at low concentrations have made oral fluid a viable matrix for drug testing. Oral fluid is an attractive matrix option due to its relative ease of collection, reduced privacy concerns for observed collections and difficulty to adulterate. The work presented here details the development and validation of a liquid chromatography tandem mass spectrometry (LC-MS-MS) method for the quantification of codeine, morphine, 6-acetylmorphine, hydrocodone, hydromorphone, oxycodone and oxymorphone in neat oral fluid. The calibration range is 0.4-150 ng/mL for 6-acetylmorphine and 1.5-350 ng/mL for all other analytes. Within-run and between-run precision were <5% for all analytes except for hydrocodone, which had 6.2 %CV between runs. Matrix effects, while evident, could be controlled using matrix-matched controls and calibrators with deuterated internal standards. The assay was developed in accordance with the proposed mandatory guidelines for opioid confirmation in federally regulated workplace drug testing. The use of neat oral fluid, as opposed to a collection device, enables collection of a single sample that can be split into separate specimens.

The Disposition of Oxycodone and Metabolite in Human Hair.

The disposition of oxycodone (OC) and metabolites in hair remains poorly characterized. We present a case involving a pharmacist in an impaired professionals' monitoring program in whom hair testing yielded OC on two occasions. On both occasions, his hair was negative for the oxymorphone (OM) metabolite at the cutoff concentration of 100 pg/mg. He claimed that, absent the detection of metabolite, the OC necessarily represented external contamination. This prompted a review of the laboratory's OC-positive hair results for the quarter April-June 2014. Overall, 466 specimens contained OC, with a mean (median) concentration of 2,375 (1,060) pg/mg. Of these OC-positive specimens, only 47 (10%) contained detectable OM. When OC was present at or below the mean (median) concentration, only 2.2% (1.3%) of specimens were OM-positive. In the setting of OC administration, the detection of OM in hair is unlikely at a cutoff concentration of 100 pg/mg. More consistent demonstration of OC metabolite(s) in hair will require the validation of methods to detect OM at lower concentrations and/or methods to detect noroxycodone.

Investigation of 4,5-epoxymorphinan degradation during analysis by HPLC.

Compounds of the 4,5-epoxymorphinan series have been shown to degrade in solution to the corresponding 2,2'-dimers when stored in amber glass HPLC vials. A colorant in the glass has been shown to catalyze the degradation. Although amber glass is routinely used to protect solutions from light degradation, it should not be used without evaluating its effect on sample stability.

Estimation of high pressure liquid chromatographic retention indices of narcotic analgetics and related drugs.

A method for the prediction of the retention index of drugs on C18 reversed-phase columns was developed and then applied to a series of drugs that were structurally related to morphine and to a series related to fentanyl. The HPLC retention index (/) of the test compounds was estimated using the equation: / = 200 pi + /ref. where pi was the sum of the Hansch substituent constants for the compound, and /ref. was the index experimentally observed for the reference compound of the series. It was also found that the observed index could be used to assign the stereochemistry of the fentanyl analogues.