Dispersive solid-phase extraction of buprenorphine from biological fluids using metal-organic frameworks and its determination by ultra-performance liquid chromatography.

In this work, various types of metal-organic frameworks were synthesized, and their affinities toward buprenorphine were evaluated using dispersive solid-phase extraction. The extracted buprenorphine was determined by ultra high performance liquid chromatography-ultraviolet detection system. The highest extraction recovery was observed by employing zeolitic imidazole framework-67. Then, a facile and fast extraction method was designed for the extraction and purification of the target drug. Optimization of the extraction method was carried out by the design of experiment approach. A linearity range of 1-1000 µg/L with the limit of detection of 0.15 µg/L and relative standard deviations (50 µg/L, n = 5) of 3.4% was obtained for standard sample analysis. Under optimized experimental and instrumental conditions, the relative recoveries were in the range of 95 to 111%. Eventually, zeolitic imidazole framework-67 was successfully employed for the extraction and determination of buprenorphine in the biological fluids with satisfactory results.

Buprenorphine Treatment for Opioid Use Disorder in Community-Based Settings: Outcome Related to Intensity of Services and Urine Drug Test Results.

BACKGROUND AND OBJECTIVES: Variables contributing to the outcome of buprenorphine treatment for opiate use disorder have been studied, including patient characteristics and the treatment approach applied. It is also valuable to study the types of clinical facilities that can affect outcome. METHODS: We evaluated patients (N = 20 993) in 573 facilities where buprenorphine was prescribed. Urine drug test results were analyzed for those (N = 13 281) who had buprenorphine prescribed at least twice in the period January 2015 through June 2017. Facilities were divided into three categories: medication management (MM) only, limited psychosocial (LP) therapy, and recovery-oriented (with more extensive counseling and a 12-step orientation) (RO). RESULTS: Urine drug tests negative for other opioids at the time of the second buprenorphine prescription were 34% for MM, 56% for LP, and 62% for RO (P < .001). A comparison was made between the most recent and the established patients at the facilities. The decrement in urinalyses positive for other opioids in this latter comparison was 3% for MM, 7% for LP, and 23% for RO (P < .001). DISCUSSION AND CONCLUSIONS: In a large sample of community settings, buprenorphine patients' urinalyses positive for opioids can vary considerably across treatment facilities, and more intensive recovery orientation may yield a better outcome in terms of secondary opioid use. SCIENTIFIC SIGNIFICANCE: The majority of buprenorphine patients are treated in community facilities. It is important that research be done by facility type in such settings in order to plan for optimal treatment. (© 2020 The Authors. The American Journal on Addictions published by Wiley Periodicals, Inc.;00:00-00).

High Prevalence of Buprenorphine in Prenatal Drug Screens in an Appalachian City.

OBJECTIVES: To define the magnitude of buprenorphine presence in the urine drug screens of pregnant women and to assess the presence of illicit buprenorphine use versus the presence of prescribed buprenorphine use. METHODS: Initial prenatal drug screen results for all pregnant patients in our practice for a 1-year period were analyzed and tabulated. RESULTS: Buprenorphine was found in the urine drug screens of 16% of pregnant patients. The presence of buprenorphine was by far the highest for any substance associated with neonatal abstinence syndrome (NAS). We estimate that the exposure to buprenorphine of approximately one-third of individuals in our population is associated with illicit buprenorphine use. CONCLUSIONS: The high rate of NAS in our region is primarily associated with both illicit and prescribed buprenorphine rather than other substances. Buprenorphine usage at the time that prenatal care is initiated, rather than opiate use at the onset of prenatal care, is the underlying factor that must be addressed if our region is to successfully combat our high rates of NAS.

Highly selective extraction and voltammetric determination of the opioid drug buprenorphine via a carbon paste electrode impregnated with nano-sized molecularly imprinted polymer.

An electrochemical sensor for the opioid drug buprenorphine (BUP) is described. Molecularly imprinted polymer nanoparticles (nanoMIP) were prepared and used to modify a carbon paste electrode (CPE). The BUP-imprinted polymer was synthesized using precipitation polymerization. The resulting polymer along with multiwalled carbon nanotubes (MWCNT) was used to fabricate the modified CPE which exhibited an anodic peak at about +0.73 V (vs. Ag/AgCl) for BUP. The MIP on the CPE functions as selective recognition element with an imprinting factor of 5.6. The assay consists of two-steps, viz. analyte extraction at the electrode surface and differential pulse voltammetric determination of BUP. The effects of various parameters on the electrochemical signal were optimized, and the selectivity of the modified CPE over cross reactants was studied. At optimum experimental conditions, the response is linear in the 1 nM to 50 µM BUP concentration range, and the detection limit is 0.6 nM (at S/N = 3). This method was applied to the determination of BUP in spiked urine with acceptable relative standard deviations (3.2-4.4%). Graphical abstract Schematic representation of buprenorphine (BUP) recognition and voltammetric determination at the surface of carbon paste electrode modified with imprinted polymer and carbon nanotubes.

Definitive urine drug testing in office-based opioid treatment: a literature review.

Individuals who receive buprenorphine treatment for opioid use disorder in office-based settings may be at risk for, or have a history of, polysubstance use. Urine drug testing is an important clinical tool for monitoring medication adherence and patient stability; and screening for illicit drug use and dangerous drug-drug interactions. This article is intended to educate practitioners in office-based opioid treatment settings on selecting appropriate substances for a definitive drug testing panel that are known to be used concurrently, sequentially, or in combination with buprenorphine for opioid use disorder. It is also intended to educate such practitioners on selecting appropriate testing technology to reduce risks to the health and safety of patients prescribed buprenorphine for opioid use disorder. In developing this article, the author conducted a search from May 2018 through December 2017 of peer-reviewed and government-supported articles in electronic databases. The literature showed that several common substances are often abused in conjunction with certain other substances, increasing the risk of serious adverse events, including death. Whether used on their own, concurrently, sequentially, or in combination, substances of abuse carry significant health risks. Definitive urine drug testing, given its high specificity and sensitivity, can accurately identify the use of specific prescription medications and illicit substances that, especially when taken with buprenorphine or other substances, may cause harm to a patient. When testing for buprenorphine and other opioids; sedatives, hypnotics, and anxiolytics; cocaine; amphetamines; and PCP and other club drugs, providers in office-based opioid treatment settings are strongly advised to use definitive urine drug tests as the primary testing methodology. In addition, practitioners must be able to identify all other substances that a patient may be consuming, taking into consideration the patient's historical and current drugs of choice, given that concurrent use with buprenorphine or other substances may cause serious adverse events. This article highlights the pressing market demand for comprehensive, definitive urine drug testing at a more reasonable cost.

Computer-aided design and synthesis of a highly selective molecularly imprinted polymer for the extraction and determination of buprenorphine in biological fluids.

Buprenorphine is widely used to aid the cessation of opioids in addicted patients. To the best of our knowledge, there is no selective extraction method for buprenorphine from biological fluids. Here, we describe the synthesis of a molecularly imprinted polymer with the aid of computational design and its application for selective extraction of buprenorphine from plasma and urine. Computational design was used to study intermolecular interactions in the pre-polymerization mixture by the comparison of the binding energy between buprenorphine (template) and functional monomers. The largest interaction energy of template-monomers was obtained at ratio of 1:5 buprenorphine/acrylic acid monomers. Afterwards, the molecularly imprinted polymer was synthesized through precipitation polymerization technique and was employed for selective extraction of buprenorphine. Optimization of various parameters of the molecularly imprinted polymer solid-phase extraction of buprenorphine was carried out by a design of experiment approach using a central composite design and the analyte was determined by employing high-performance liquid chromatography with UV detection. Equilibrium isotherms were studied, and results revealed that the sorption process was in adoption with Langmuir model. Maximum enrichment capacity and Langmuir constant were calculated as 18.2 mg/g and 0.797 L/mg, respectively. Kinetic studies indicated the sorption process followed a pseudo-second-order model.

Quantitative testing of buprenorphine and norbuprenorphine to identify urine sample spiking during office-based opioid treatment.

BACKGROUND: Patients may spike urine samples with buprenorphine during office-based opioid treatment to simulate adherence to prescribed buprenorphine, potentially to conceal diversion of medications. However, routine immunoassay screens do not detect instances of spiking, as these would simply result in a positive result. The aim of this study was to report on the experience of using quantitative urine testing for buprenorphine and norbuprenorphine to facilitate the identification of urine spiking. METHODS: This is a retrospective chart review of 168 consecutive patients enrolled in outpatient buprenorphine treatment at an urban academic medical setting between May 2013 and August 2014. All urine samples submitted were subjected to quantitative urine toxicology testing for buprenorphine and norbuprenorphine. Norbuprenorphine-to-buprenorphine ratio of less than 0.02 were further examined for possible spiking. Demographic and clinical variables were also extracted from medical records. Clinical and demographic variables of those who did and did not spike their urines were compared. Statistically significant variables from the univariate testing were entered as predictors of spiking in a regression analysis. RESULTS: A total of 168 patients were included, submitting a total of 2275 urine samples. Patients provided on average 13.6 (SD = 9.9) samples, and were in treatment for an average 153.1 days (SD = 142.2). In total, 8 samples (0.35%) from 8 patients (4.8%) were deemed to be spiked. All of the samples suspected of spiking contained buprenorphine levels greater than 2000 ng/mL, with a mean norbuprenorphine level of 11.9 ng/mL. Spiked samples were submitted by 6 patients (75.0%) during the intensive outpatient (IOP) phase of treatment, 2 patients (25.0%) during the weekly phase, and none from the monthly phase. Regression analysis indicated that history of intravenous drug use and submission of cocaine-positive urine samples at baseline were significant predictors of urine spiking. CONCLUSIONS: Even though only a small number of patients were identified to have spiked their urine samples, quantitative testing may help identify urine spiking during office-based opioid treatment with buprenorphine.

Interpretation of urine drug testing results in patients using transdermal buprenorphine preparations for the treatment of chronic noncancer pain.

OBJECTIVE: To determine whether the prevailing liquid chromatography and tandem mass spectroscopy assay (LC-MS/MS) assay designed to monitor buprenorphine compliance of the sublingual formulation used in the substance abuse treatment setting can be extrapolated to the transdermal formulation used in the chronic pain treatment setting, which is 1000-fold less concentrated. DESIGN: Retrospective chart review. SUBJECTS: Self-reported compliant patients using the transdermal or sublingual formulations of buprenorhphine. Transdermal patch application was also visually confirmed during clinic visits. METHODS: Urine drug test results from a LC-MS/MS were compared between samples from transdermal and sublingual patients. RESULTS: While all sublingual patients tested positive for at least one metabolite of buprenorphine, only 69% of the transdermal patients did so. In addition, the most abundant metabolite in the transdermal patients was buprenorphine-glucuronide, as compared with norbuprenorphine-glucuronide in sublingual patients. CONCLUSIONS: These data suggest that currently available urine drug tests for buprenorphine, including the more expensive LC-MS/MS based assays, may not be sufficiently sensitive to detect the metabolites from transdermal buprenorphine patients. This study highlights the need to evaluate the value and sensitivity of urine drug tests given the wide range of buprenorphine dosing in clinical practice. These results underscore the need for additional cost benefit analyses comparing different confirmatory drug testing techniques including many commercially available drug testing options. © 2014 Wiley Periodicals, Inc.

Application of drug testing using exhaled breath for compliance monitoring of drug addicts in treatment.

AIM: Exhaled breath has recently been identified as a possible matrix for drug testing. This study explored the potential of this new method for compliance monitoring of patients being treated for dependence disorders. METHODS: Outpatients in treatment programs were recruited for this study. Urine was collected as part of clinical routine and a breath sample was collected in parallel together with a questionnaire about their views of the testing procedure. Urine was analyzed for amphetamines, benzodiazepines, cannabis, cocaine, buprenorphine, methadone and opiates using CEDIA immunochemical screening and mass spectrometry confirmation. The exhaled breath was collected using the SensAbues device and analyzed by mass spectrometry for amphetamine, methamphetamine, diazepam, oxazepam, tetrahydrocannabinol, cocaine, benzoylecgonine, buprenorphine, methadone, morphine, codeine and 6-acetylmorphine. RESULTS: A total of 122 cases with parallel urine and breath samples were collected; 34 of these were negative both in urine and breath. Out of 88 cases with positive urine samples 51 (58%) were also positive in breath. Among the patients on methadone treatment, all were positive for methadone in urine and 83% were positive in breath. Among patients in treatment with buprenorphine, 92% were positive in urine and among those 80% were also positive in breath. The questionnaire response documented that in general, patients accepted drug testing well and that the breath sampling procedure was preferred. CONCLUSION: Compliance testing for the intake of prescribed and unprescribed drugs among patients in treatment for dependence disorders using the exhaled breath sampling technique is a viable method and deserves future attention.

Laboratory and clinical evaluation of on-site urine drug testing.

AIM: Products for on-site urine drug testing offer the possibility to perform screening for drugs of abuse directly at the point-of-care. This is a well-established routine in emergency and dependency clinics but further evaluation of performance is needed due to inherent limitations with the available products. METHODS: Urine drug testing by an on-site product was compared with routine laboratory methods. First, on-site testing was performed at the laboratory in addition to the routine method. Second, the on-site testing was performed at a dependency clinic and urine samples were subsequently sent to the laboratory for additional analytical investigation. RESULTS: The on-site testing products did not perform with assigned cut-off levels. The subjective reading between the presence of a spot (i.e. negative test result) being present or no spot (positive result) was difficult in 3.2% of the cases, and occurred for all parameters. The tests performed more accurately in drug negative samples (specificity 96%) but less accurately for detecting positives (sensitivity 79%). Of all incorrect results by the on-site test the proportion of false negatives was 42%. The overall agreement between on-site and laboratory testing was 95% in the laboratory study and 98% in the clinical study. CONCLUSION: Although a high degree of agreement was observed between on-site and routine laboratory urine drug testing, the performance of on-site testing was not acceptable due to significant number of false negative results. The limited sensitivity of on-site testing compared to laboratory testing reduces the applicability of these tests.

Longitudinal missing data strategies for substance use clinical trials using generalized estimating equations: an example with a buprenorphine trial.

OBJECTIVE: A review of substance use clinical trials indicates that sub-optimal methods are the most commonly used procedures to deal with longitudinal missing information. METHODS: Listwise deletion (i.e., using complete cases only), positive urine analysis (UA) imputation, and multiple imputation (MI) were used to evaluate the effect of baseline substance use and buprenorphine/naloxone tapering schedule (7 or 28 days) on the probability of a positive UA (UA+) across the 4-week treatment period. RESULTS: The listwise deletion generalized estimating equations (GEE) model demonstrated that those in the 28-day taper group were less likely to submit a UA+ for opioids during the treatment period (odds ratios (OR) = 0.57, 95% confidence interval (CI): 0.39-0.83), as did the positive UA imputation model (OR = 0.43, CI: 0.34-0.55). The MI model also demonstrated a similar effect of taper group (OR = 0.57, CI: 0.42-0.77), but the effect size was more similar to that of the listwise deletion model. CONCLUSIONS: Future researchers may find utilization of the MI procedure in conjunction with the common method of GEE analysis as a helpful analytic approach when the missing at random assumption is justifiable.

[Study on the distribution of buprenorphione in the bodies of the rabbits].

OBJECTIVE: To investigate the distribution of buprenorphione in the bodies of rabbits. METHODS: Buprenorphione was administrated to rabbits orally or by intravenous injection (0.04 mg/kg buprenorphione). Two hours after administration, rabbits were killed and their blood, urine, liver, kidney, lung, stomach, brain, heart, stomach content and feces were collected. The concentrations of buprenorphione in these body fluids and tissues were determined by liquid chromatography-mass spectrometry (LC-MS). RESULTS: The results show the distribution of buprenorphione in rabbit's body: urine>stomach content>brain >heart >stomach>lung> kidney > liver > blood> feces. CONCLUSION: The method developed can be used for the detection of buprenorphione in biological fluids and tissues in forensic practice. Urine is the preferred sample for screening for buprenorphione abuse.

An Opioid Hiding in Plain Sight: Loperamide-Induced False-Positive Fentanyl and Buprenorphine Immunoassay Results.

BACKGROUND: Loperamide (Imodium®), a commonly used anti-diarrheal, is a mu opioid receptor agonist that, like all opioids, reduces gastrointestinal tract peristalsis. Loperamide is considered to have low abuse potential as it does not produce an analgesic or euphoric effect due to low bioavailability and first-pass metabolism. However, reports of individuals misusing loperamide through the use of super-therapeutic doses, alone or in combination with P-glycoprotein and/or CYP450 enzyme inhibitors, is increasing. We hypothesized that loperamide could potentially cross-react with laboratory immunoassay drug screens. METHODS: Drug-free urine was spiked with loperamide or its principal metabolite, N-desmethyl loperamide (dLop), and assayed on multiple fentanyl and buprenorphine assays. Fentanyl immunoassay screen-positive results at one institution were examined by high-resolution mass spectrometry (MS) for the presence of loperamide and quantified by liquid chromatography- tandem MS when positive. RESULTS: Loperamide produced positive results on the Thermo DRI Fentanyl and Immunalysis Fentanyl assays at concentrations greater than 5.72 mg/L and 23.7 mg/L. dLop generated positive results for the Thermo DRI and Immunalysis fentanyl assays at concentrations exceeding 6.9 mg/L and 35.7 mg/L. dLop also produced positive buprenorphine results on the Thermo CEDIA buprenorphine assay at concentrations exceeding 12.2 mg/L. High-resolution MS analysis of 225 fentanyl immunoassay positives (Thermo DRI) yielded 5 specimens containing loperamide and/or dLop, 4 of which contained measurable quantities of fentanyl in addition to loperamide/dLop. CONCLUSIONS: Laboratories using these assays should be aware of the potential for false-positive screening results due to the presence of high concentrations of loperamide and its metabolite dLop.

Investigation of buprenorphine-related deaths using urinary metabolite concentrations.

Quantitative analysis of postmortem urine, instead of blood, for buprenorphine and metabolites may provide additional evidence for the diagnosis of fatal buprenorphine poisoning. In this study, 247 autopsy urine samples, previously testing positive for buprenorphine or norbuprenorphine, were quantitatively reanalysed with a recently developed liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for unconjugated buprenorphine (BUP), norbuprenorphine (NBUP), naloxone (NAL), and their respective conjugated metabolites, buprenorphine glucuronide (BUPG), norbuprenorphine glucuronide (NBUPG), and naloxone glucuronide (NALG). The cases were divided, according to medical examiners' decision, to buprenorphine poisonings and other causes of death. The groups were compared for urinary concentrations and metabolite concentration ratios of the six analytes. All median concentrations were higher in the buprenorphine poisoning group. The median concentration of BUPG was significantly higher and the median metabolite ratios NBUP/BUP, NBUPG/BUPG, and NBUPtotal/BUPtotal were significantly lower in poisonings than in other causes of death. Naloxone-related concentrations and ratios were not significantly different between the groups.

Norbuprenorphine Interferences in Urine Drug Testing LC-MS-MS Confirmation Methods from Quetiapine Metabolites.

Norbuprenorphine interferences were observed in urine drug testing LC-MS-MS confirmation methods used to assess patient compliance with prescribed buprenorphine for chronic pain and opioid use disorder. The interferences were observed in the norbuprenorphine MS-MS transitions, m/z 414.4/83.1 and 414.4/187.2, at and near the norbuprenorphine retention time at multiple laboratories using different sample preparation procedures and chromatographic conditions. When the interferences were present, a norbuprenorphine result could not be reported. Upon investigation, the interferences were correlated with prescribed quetiapine (Seroquel, Seroquel XR), a second-generation antipsychotic medication approved for the treatment of schizophrenia, bipolar disorder and more recently as an adjunct treatment for major depressive disorder. In addition to the approved indications, quetiapine is prescribed off-label for other conditions including insomnia and anxiety disorders. Off-label prescribing has increased in recent years, thereby exacerbating this analytical issue. Here, we present the study of four quetiapine metabolites found to have significant direct or potential interferences in norbuprenorphine quantitation. The four metabolites were putatively identified as two hydroxyquetiapine acids differing in the site of hydroxylation and a quetiapine sulfoxide acid diastereomer pair. As a result of this study, interference-free norbuprenorphine MS-MS transitions, m/z 414.4/340.2 and 414.4/326.1, were found that were selective for norbuprenorphine while maintaining an acceptable 10 ng/mL lower limit of quantitation.

Preliminary buprenorphine sublingual tablet pharmacokinetic data in plasma, oral fluid, and sweat during treatment of opioid-dependent pregnant women.

BACKGROUND: Buprenorphine is currently under investigation as a pharmacotherapy to treat pregnant women for opioid dependence. This research evaluates buprenorphine (BUP), norbuprenophine (NBUP), buprenorphine-glucuronide (BUP-Gluc), and norbuprenorphine-glucuronide (NBUP-Gluc) pharmacokinetics after high-dose (14-20 mg) BUP sublingual tablet administration in three opioid-dependent pregnant women. METHODS: Oral fluid and sweat specimens were collected in addition to plasma specimens for 24 hours during gestation weeks 28 or 29 and 34, and 2 months after delivery. Time to maximum concentration was not affected by pregnancy; however, BUP and NBUP maximum concentration and area under the curve at 0 to 24 hours tended to be lower during pregnancy compared with postpartum levels. RESULTS: Statistically significant but weak positive correlations were found for BUP plasma and OF concentrations and BUP/NBUP ratios in plasma and oral fluid. Statistically significant negative correlations were observed for times of specimen collection and BUP and NBUP oral fluid/plasma ratios. BUP-Gluc and NBUP-Gluc were detected in only 5% of oral fluid specimens. In sweat, BUP and NBUP were detected in only four of 25 (12 or 24 hours) specimens in low concentrations (less than 2.4 ng/patch). CONCLUSION: These preliminary data describe BUP and metabolite pharmacokinetics in pregnant women and suggest that, like methadone, upward dose adjustments may be needed with advancing gestation.

Fast GC-MS method for the simultaneous screening of THC-COOH, cocaine, opiates and analogues including buprenorphine and fentanyl, and their metabolites in urine.

A fast gas chromatography (GC)-MS method has been developed and validated for the simultaneous screening of different classes of drugs of abuse in urine. Tetrahydrocannabinol metabolite, cocaine, opiates such as morphine, O-6-monoacetylmorphine (O-6-MAM), codeine, opioids such as buprenorphine, methadone, pentazocine, fentanyl and analogues and their main metabolites can be detected and quantified after a simple liquid-liquid extraction in alkaline conditions and derivatisation to obtain the corresponding trimethylsilyl derivatives. The chromatographic separation is performed in a total time of 6 min, using a short GC column (5% phenyl methyl silicone, 10-m length × 0.18-mm internal diameter). The Limits of Detection are satisfactory for forensic purposes for all the substances; the repeatability of concentrations (percent coefficients of variation) are always lower than 15% at high and low concentration levels, and accuracy, intended as % error on the true value, is always lower than 15% for all the analytes. The method can successfully be applied for screening analyses in many fields of forensic toxicology.

Unusual false-positive case of urinary screening for buprenorphine.

Buprenorphine is a centrally acting analgesic drug that is administered for the management of opioid dependence and as an analgesic drug for the treatment of chronic pain. The growing use of this substance has determined an increased need for laboratory testing for either detection and confirmation of the illicit use or monitoring compliance as a substitution therapy for opioid dependence. We describe here the case of urinary sample adulteration with exogenous buprenorphine (6,952 ng/ml), which has led to afalse-positive immunoassay test result (14.9 ng/ml) on a subsequent sample due to a phenomenon of instrumental carry-over. This unusual case confirms the importance to take into account adulteration when screening urines for buprenorphine in patients undergoing substitution therapy for opioid dependence, routinely perform a confirmation assay on positive samples, and rule out instrumental carry-over.

Determination of buprenorphine, norbuprenorphine, naloxone, and their glucuronides in urine by liquid chromatography-tandem mass spectrometry.

A liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of buprenorphine (BUP), norbuprenorphine (NBUP), naloxone (NAL), and their glucuronide conjugates BUP-G, NBUP-G, and NAL-G in urine samples was developed. The method, omitting a hydrolysis step, involved non-polar solid-phase extraction, liquid chromatography on a C18 column, electrospray positive ionization, and mass analysis by multiple reaction monitoring. Quantification was based on the corresponding deuterium-labelled internal standards for each of the six analytes. The limit of quantification was 0.5 µg/L for BUP and NAL, 1 µg/L for NAL-G, and 3 µg/L for NBUP, BUP-G, and NBUP-G. Using the developed method, 72 urine samples from buprenorphine-dependent patients were analysed to cover the concentration ranges encountered in a clinical setting. The median (maximum) concentration was 4.2 µg/L (102 µg/L) for BUP, 74.7 µg/L (580 µg/L) for NBUP, 0.9 µg/L (85.5 µg/L) for NAL, 159.5 µg/L (1370 µg/L) for BUP-G, 307.5 µg/L (1970 µg/L) for NBUP-G, and 79.6 µg/L (2310 µg/L) for NAL-G.

Are point-of-care urine drug testing devices suitable for antenatal drug screening? A study verifying the Alere® Drug Screen Test Cup for the detection of six classes of drug in a pregnant population.

BACKGROUND: Currently, there are no national guidelines for antenatal drug testing. At Colchester Hospital, we use a strategy of screen-only using point-of-care testing to detect illicit drug use in pregnancy. To determine the suitability of this approach, we have compared the results of urine analysis by point-of-care testing with another NHS specialist clinical toxicology service that uses confirmation mass spectrometry. METHODS: A total of 482 anonymized random urine specimens from antenatal clinics were tested for six drug classes: amphetamine, benzodiazepines, buprenorphine, cocaine, methadone and opiates using the Alere™ Drug Screen Urine Test Cup. The manufacturer's claims for positive cut-off and result stability were verified using spiked blank urine. Confirmatory testing was performed using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) for detection of 26 individual drugs. RESULTS: Of 473 urine samples with adequate volume for point-of-care screening, 4.4% tested positive: 19 opiate and 2 cocaine. Concordance between point-of-care screening and UPLC-MS/MS confirmation was 97.9% for all drugs and 78.9% for opiates. Using spiked urine, only positive results for opiates were stable when read up to the manufacturer's recommended time of 60 min. CONCLUSIONS: The key advantages of using point-of-care devices to detect drug use in pregnancy are that is convenient and cheap. However, the clinical utility of point-of-care testing is limited by its poor sensitivity. Best practice is to confirm results using a more specific and sensitive method. As a result of this study, we are now reviewing our own procedures to consider introducing routine confirmation by mass spectrometry.