Assessment of mass spectrometry-based pain management testing in clinical laboratories across North America.

BACKGROUND: Urine drug testing (UDT) is a useful tool in monitoring compliance to prescribed medication and can also help identify behaviors of drug misuse, abuse, and diversion. Mass spectrometry (MS)-based screening is recommended as the first-line of UDT for pain management patients; however, this testing comes with an inherent lack of standardization in methodologies and various analytical challenges. The objective of this study was to assess the current state of UDT for pain management in a cross-section of clinical laboratories in North America. MATERIALS AND METHODS: A total of 10 blinded urine samples were sent to 6 laboratories across the United States and Canada. Urine samples containing drugs and/or metabolites of interest were included to represent different clinical scenarios commonly seen in pain management settings. Assessment was based on the ability of the laboratories to correctly identify drugs and provide a meaningful interpretation of the findings (when offered by the performing laboratory). RESULTS: Across the laboratories involved in the study, 85% of tests correctly identified and appropriately reported the drugs present in the urine samples. Similarly, 84% of samples were considered to have an accurate interpretation included in the UDT report. Out of the total number of drugs included in the samples, 11% were not offered on every test menu. CONCLUSIONS: This study revealed the lack of standardization in pain management UDT performed in a limited cross-section of clinical laboratories across North America.

Anodyne by Design; Measuring the Prevalence of Esoteric Designer Opioids in Pain Management Patients.

The recent increase in illicit opioids sold on the black market, cut into heroin and masqueraded as prescription pills prompts a significant public health concern. Most designer opioids possess unknown potencies and unknown pharmacokinetics and their unregulated, variable dosages lead to rashes of overdoses. Additionally, many of the designer opioids, especially the fentanyl analogs are significantly more potent than heroin. High-profile cases involving overdoses of U-47700 and carfentanil have been reported in the media; however, the true prevalence of these and other designer opioids is unknown. Independent LC-MS-MS screen and confirmation methods have been developed and validated to identify and quantify fentanyl, and 18 designer opioids and their metabolites; methods were then exercised on urine specimens from contract pain management clients. Assuming patients in a pain management program may have a higher probability to seek out self-medication, samples from pain management patients were investigated for designer opioids. Similarly, pain management patients identified as using heroin may be more likely to experiment with or be accidentally exposed to designer opioids, specimens screening positive for the heroin metabolite 6-acetylmorphine were specifically chosen for designer opioid screening. Within this small group of pain management and heroin-positive samples, nine designer opioids were detected at a total prevalence of 25%. When screening random pain management samples not positive for heroin, a considerably lower percentage of samples (<1%) were identified as positive for designer opioids. Furanyl fentanyl, fluorobutyryl fentanyl and acetylfentanyl were the most prevalent designer opioids detected in both test groups.

Quantification of a methadone metabolite (EDDP) in urine: assessment of compliance.

OBJECTIVE: To investigate the possibility of utilizing the ratio of the methadone metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), to urine creatinine to develop a regression model that would predict drug adherence in patients prescribed methadone for either pain management or drug addiction. DESIGN: Retrospective study. SETTING: Marshfield Clinic-Lakeland Center, one of 41 regional centers that make up Marshfield Clinic, a large, private, multi-specialty healthcare institution in central Wisconsin. PARTICIPANTS: Patients receiving methadone treatment for substance abuse or chronic pain. Group 1 was an initial pilot group consisting of 7 patients who were followed for a 4-month period. Group 2 consisted of 33 patients who were followed over a 28-month period. METHODS: Age, gender, weight, height, methadone dosage, quantitative urine creatinine and EDDP levels, reported compliance/non-compliance, and relevant clinical cofactors were retrospectively abstracted from the patients' medical records. Log-log regression analyses were used to model EDDP and the EDDP/creatinine ratio from urine screening results as functions of methadone dose, and in the larger cohort (group 2), body size, gender and age. The coefficient of determination adjusted for the number of predictor terms (R(adj)(2)) was reported as a measure of model fit. RESULTS: For group 1 data, there was a significant positive relation (P<0.001) but also substantial variability (R(adj)(2) = 0.49). Adjustment for creatinine through the EDDP/creatinine ratio provided a tighter relation (R(adj)(2) = 0.95). Similarly, for group 2 data, there was a significant positive relation (P=0.001) and substantial variability (R(adj)(2) = 0.53). Adjustment for creatinine through EDDP/creatinine ratios provided a substantially stronger relation (R(adj)(2) = 0.73). Gender and age showed no evidence of association with the EDDP/creatinine ratio (P=0.60 and P=0.51, respectively). Body size was significant in the model, both when measured by body surface area and by lean body weight, and improved the prediction when added to our model (R(adj)(2) = 0.80). CONCLUSION: For the first time, urine analyses may be used to monitor methadone over- or under-use in a clinical setting, regardless of the state of patient hydration or the manipulation of a sample by addition of another substance, such as bleach, soap, or even methadone, which could render an appropriate sample inappropriate or an inappropriate sample appropriate. A similar approach may prove useful for other drug treatments, allowing for more accurate monitoring of commonly abused prescription medications.

Does random urine drug testing reduce illicit drug use in chronic pain patients receiving opioids?

BACKGROUND: Prescription drug abuse and illicit drug use are common in chronic pain patients. Adherence monitoring with screening tests, and urine drug testing, periodic monitoring with prescription monitoring programs, has become a common practice in recent years. Random drug testing for appropriate use of opioids and use of illicit drugs is often used in pain management practices. Thus, it is expected that random urine drug testing will deter use of illicit drugs, and also improve compliance. OBJECTIVES: To study the prevalence of illicit drug use in patients receiving opioids for chronic pain management and to compare the results of illicit drug use with the results from a previous study. DESIGN: A prospective, consecutive study. SETTING: Interventional pain management practice setting in the United States. METHODS: A total of 500 consecutive patients on opioids, considered to be receiving stable doses of opioids supplemental to their interventional techniques, were studied by random drug testing. Testing was performed by rapid drug screen. Results were considered positive if one or more of the monitored illicit drugs including cocaine, marijuana (THC), methamphetamine or amphetamines were present. RESULTS: Illicit drug use was evident in 80 patients, or 16%, with marijuana in 11%, cocaine in 5%, and methamphetamine and/or amphetamines in 2%. When compared with previous data, the overall illicit drug use was significantly less. Illicit drug use in elderly patients was absent. CONCLUSION: The prevalence of illicit drug abuse in patients with chronic pain receiving opioids continues to be a common occurence. This study showed significant reductions in overall illicit drug use with adherence monitoring combined with random urine drug testing.