Observations on the effects of buprenorphine and methadone on illicit drug use.

OBJECTIVE: To determine if the agonistic effects of buprenorphine and methadone affect drug use. METHOD: Quantitative examination of urine drug concentrations of patients treated with buprenorphine and methadone. RESULTS: Patients on buprenorphine had less opioid and methamphetamine drug use than those on methadone. CONCLUSION: Patients on buprenorphine therapy appear to use less illicit drugs.

Monitoring buprenorphine in patients on medication-assisted treatment.

BACKGROUND: Buprenorphine is used for medication-assisted treatment of opioid dependence. PURPOSE: Monitoring of medication adherence involves testing of urine or oral fluid for the drug or its metabolite. METHODS: Quantitative results using liquid chromatography tandem mass spectrometer testing defined the excretion pattern of the drug and its metabolites. RESULTS: Frequency distribution curves of buprenorphine and norbuprenorphine describe the expected drug concentrations of patients on this medication. CONCLUSION: Urine and oral fluid drug testing can be used to monitor adherence in this population.

Letter to Editor: Observations of Deception in Urine Drug Testing.

OBJECTIVE: Determining deception in urine drug testing. Some of the patients undergoing urine drug tests have not taken the prescribed drug and attempt to deceive the laboratory test by placing the parent drug in the collection cup. METHODS: One of the ways to determine if this is occurring is to monitor the major metabolite of the drug. By using the metabolite/parent drug ratio this attempt at deception can be uncovered. RESULTS: Of the five drugs we examined, oxycodone, hydrocodone, buprenorphine, methadone, and fentanyl, we found buprenorphine to be the most prevalent drug to this type of deception. CONCLUSION: Deception can be identified using the metabolite/parent drug ratio.

Estimates of Drug Metabolism Using Drug Excretion Concentrations.

We propose that quantitative urine drug concentrations from LC-MS/MS measurements can be used to estimate zero and first order pharmacokinetics of the drugs oxycodone, hydrocodone, buprenorphine, methadone, and fentanyl. We observed the ratio of metabolite to parent drug could be used for this estimate. As the amount of observed parent drug increased, the metabolic ratio decreased, indicating a shift from first order to zero order metabolism. After making assumptions of bioavailability, percent of drug excreted into urine, we developed estimates of the saturating dosages for these drugs.

Update: Correlation of Fentanyl Positive Drug Screens with other Medications in Patients from Pain, Rehabilitation and Behavioral Programs.

OBJECTIVE: To monitor fentanyl polydrug use over past six years. METHOD: Calculate percent of fentanyl and other drugs positive in urine drug tests. RESULTS: Percent of fentanyl positive drug tests remained unchanged, but increases in fentanyl/methamphetamine and fentanyl/marijuana were observed. CONCLUSIONS: Fentanyl laced illicit drugs remain a major substance abuse problem.

Reduction of Drug-Drug Interaction Risk; CDC Guidelines Influence on Opiate Benzodiazepine Prescribing.

We examined the results of 1.3 million drug tests performed on patients being monitored for compliance with pain medications and substance abuse rehabilitation to determine if the 2016 CDC prescribing guidelines had any impact on opiate benzodiazepine use. We observed that the combination of the opiate drugs morphine, oxycodone, and hydrocodone with the benzodiazepine metabolites oxazepam, alphahydroxyalprazolam, and 7-aminoclonazepam showed many patients were on a combination of these drugs. This ranged from approximately 9 to 16%. There was considerable variability between opiate drug pairs, but there was a general trend to fewer patients on the combination of opiate-benzodiazepine over the 2016 to 2019 time frame.

Correlation of Fentanyl Positive Drug Screens with Other Medications in Patients from Pain, Rehabilitation and Behavioral Programs.

Fentanyl has been associated with many drug overdose deaths; its presence in many street drugs has been postulated to be increasing. We examined 1.3 million urine drug tests from April 2016 to April 2019 for fentanyl and other drugs. The highest relationship was observed with heroin. Approximately 30%-40% of the drug tests positive for the heroin metabolite 6-monacetylmorphine (6-MAM) were also positive for fentanyl. There was a large variance over time, but the percent positive in 2016 and 2019 were similar. In contrast, there was a definite increase in the presence of fentanyl with cocaine and methamphetamine. There was not a large increase over time associated with methadone, buprenorphine, and marijuana.

Lower Cutoffs for LC-MS/MS Urine Drug Testing Indicates Better Patient Compliance.

BACKGROUND: Urine drug testing is used by health care providers to determine a patient's compliance to their prescribed regimen and to detect non-prescribed medications and illicit drugs. However, the cutoff levels used by clinical labs are often arbitrarily set and may not reflect the urine drug concentrations of compliant patients. OBJECTIVES: Our aim was to test the hypothesis that commonly used cutoffs for many prescribed and illicit drugs were set too high, and methods using these cutoffs may yield a considerable number of false-negative results. The goals of this study were to outline the way to analyze patient results and estimate a more appropriate cutoff, develop and validate a high sensitivity analytical method capable of quantitating drugs and metabolites at lower than the commonly used cutoffs, and determine the number of true positive results that would have been missed when using the common cutoffs. STUDY DESIGN: This was a retrospective study of urine specimens submitted for urine drug testing as part of the monitoring of prescription drug compliance described in chronic opioid therapy treatment guidelines. SETTING: The study was set in a clinical toxicology laboratory, using specimens submitted for routine analysis by health care providers in the normal course of business. METHODS: Lognormal distributions of test results were generated and fitted with a trendline to estimate the required cutoff level necessary to capture the normal distributions of each drug for the patient population study. A validated laboratory derived liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis capable of achieving the required cutoff levels was developed for each drug and/or metabolite. RESULTS: The study shows that a lognormal distribution of patient urine test results fitted with a trendline is appropriate for estimating the required cutoff levels needed to assess medication adherence. The study showed a wide variation in the false-negative rate, ranging from 1.5% to 94.3% across a range of prescribed and illicit drugs. LIMITATIONS: The patient specimens were largely sourced from patients in either a long-term pain management program or in treatment for substance use disorder in the US. These specimens may not be representative of patients in other types of treatment or in countries with different approaches to these issues. CONCLUSIONS: The high-sensitivity method reduces false-negative results which could negatively impact patient care. Clinicians using less sensitive methods for detecting and quantifying drugs and metabolites in urine should exercise caution in assessing patient adherence using and changing the treatment plan based on those results. KEY WORDS: Urine drug testing, patient adherence, clinical toxicology, immunoassay, LC-MS, definitive drug testing, REMS, negative test results, false negative.

A sensitive assay for urinary cocaine metabolite benzoylecgonine shows more positive results and longer half-lives than those using traditional cut-offs.

Cocaine is a common drug of abuse. To detect its use, a screening detection concentration for the cocaine metabolite benzoylecgonine is commonly set at 150 ng/mL and its confirmatory cut-off is set at 100 ng/mL. Studies have suggested that these cut-offs may be set too high, allowing some patients with this substance abuse problem to be missed or improperly monitored. With the advent of liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology it is possible to reliably detect and quantify lower concentrations of its metabolite benzoylecgonine as part of a larger drug panel. One purpose of the study was to establish if there was a significant increase in detection of cocaine use with a ten-fold more sensitive cut-off. A very sensitive dilute and shoot assay for benzoylecgonine was developed with a lower limit of quantitation of 5 ng/mL. Validation of the 5 ng/mL cut-off was achieved by plotting all the positive cocaine observations as a frequency distribution on a logarithmic scale. The number of positive results with measurable concentrations below the typical industry 100 ng/mL cut-off level but above the high sensitivity 5 ng/mL cut-off level was observed to be 51.9% of the observed positives. The lower cut-off also allowed a re-evaluation of the window of detection after cessation of use. It was observed to be between 17 and 22 days. © 2016 Precision Diagnostics, LLC. Drug Testing and Analysis published by John Wiley & Sons, Ltd.

Simultaneous determination of Maillard reaction impurities in memantine tablets using HPLC with charged aerosol detector.

A gradient high performance liquid chromatographic (HPLC) method using charged aerosol detection (CAD) was developed for the simultaneous determination of impurities formed by the Maillard reaction in memantine tablets. These impurities were a memantine-lactose adduct (ML), a memantine-dimethylamino glycine adduct (DMAG), a memantine-galactose adduct (MGAL), and a memantine-glucose adduct (MGLU). The chromatographic separation was performed on a Synergy Hydro RP column (100 mm×3 mm, 2.5 µm particles) from Phenomenex with gradient elution using mobile phases consisting of 0.6% (v/v) of heptafluorobuturic acid (HFBA) in two acetonitrile-isopropyl alcohol-water mixtures. The method validation for the impurities included linearity, accuracy by spike recovery, precision, limits of detection and quantitation, and robustness. The method was sensitive for these non-chromophoric impurities down to 0.4-0.6 µg/mL (0.02-0.03% of the memantine drug substance). The effect of mobile phase HFBA concentration on chromatographic resolution and peak shape was investigated, and the effect of sample diluent acidification on method accuracy via spike recovery was studied. The operational simplicity of the CAD detector for routine quality control has been demonstrated.