Urine drug screening: A guide to monitoring Tx with controlled substances.

Avoid error by ordering the appropriate test at a risk-based frequency. Be alert to sources of false-positives and adulteration. Be careful not to overreact to unexpected results.

Systematic Error for Extraction of Controlled Substances from Plant/Fungal Materials.

The aim of this work was to investigate the applicability of a mathematical model developed for the description of supercritical fluid extraction (SFE) of cannabinoids from marijuana and hashish for liquid extraction of other substances. The mentioned model is applicable for dynamic SFE whose implementation is analogous to liquid-solid extraction in quasi-counter current mode. According to this model, quasi-counter current liquid-solid extractions were designed by calculation of component transport constants for extractions of psilocin from hallucinogenic mushroom, mescaline from hallucinogenic cactus, harmine from tropical lyan and salvinorin A from hallucinogenic sage. The mentioned model was found to be suitable for the determination of extraction time needed to reach a predefined extraction recovery for quasi-counter current liquid-solid extractions, as well, which allows the elimination of systematic error caused by the non-extracted part. The calculated component transport constants predict the expectable velocity of the extraction, i.e., the higher the component transport constant is, the higher the extraction velocity is. For mushrooms, it could be stated that preliminary treatment of mushrooms with liquid nitrogen significantly increases the extractability of psilocin.

Evaluation of the exposure prediction component of Control of Substances Hazardous to Health Essentials.

The exposure prediction component of the Control of Substances Hazardous to Health (COSHH) Essentials model (paper version) was evaluated using field measurements from National Institute of Occupational Safety and Health (NIOSH) Health Hazard Evaluation (HHE) reports. Overall 757 measured exposures for 94 similar exposure groups (SEGs) were compared with the COSHH Essentials predicted exposure range (PER). The SEGs were stratified based on the magnitude of measured exposures (high, medium, or low) and physical state of the substance (vapor or particulate). The majority of measured exposures observed involved low-level exposure to vapors; thus, overall findings from the current study are limited to low-level vapor exposure scenarios. Overall, the exposure prediction component of COSHH Essentials vastly overestimated low-level exposures to vapors. This study went beyond the scope of previous studies and investigated which model components led to the overestimation. It was concluded that COSHH Essential's tendency to overestimate was due to multiple complex interactions among model components. Overall, the magnitude of overestimation seems to increase exponentially as values for predictor variables increase. This is likely due to the log-based scale used by the model to allocate concentration ranges. In addition, the current banding scheme used to allocate volatility appears to play a role in the overestimation of low-level exposures to vapors.

Evaluation of Suspected Counterfeit Pharmaceutical Tablets Declared to Contain Controlled Substances Using Handheld Raman Spectrometers.

This study describes the performance of handheld Raman devices for determining whether suspect pharmaceutical tablets declared to contain controlled substances were consistent with authentic (CWA) or not consistent with authentic (NCWA) tablets using a simple, rapid, field-friendly method capable of being used by nonexperts. Twenty-five authentic products and 84 known NCWA tablets were examined using three "parent" devices for a total of 327 analyses. On average, the parent devices yielded a true pass rate of 100%, a true fail rate of 98.4%, a false pass rate of 1.6%, and a false fail rate of 0%. The methods/libraries were then transferred to 13 identical "daughter" devices, which were used to examine 10 suspect finished dosage forms in duplicate (six known NCWA tablets and four authentic tablets) for a total of 260 measurements. On average, the daughter devices had a true pass rate of 100%, a true fail rate of 95.5%, a false pass rate of 4.5%, and a false fail rate of 0.0%. These data demonstrate that the parent-daughter electronic transfer method was successful, which permits the ability to develop methods in the laboratory that can be seamlessly pushed out to field devices. The methods can then be used to (i) prioritize samples for additional testing using other more time-consuming laboratory-based techniques needed to detect and quantify active ingredients and (ii) help support the interdiction of dangerous tablets at ports of entry, thereby preventing them from reaching the supply chain.

Forensic Toxicology Perspectives of Methadone-associated Deaths in Tehran, Iran, a 7-year Overview.

Methadone has a long history of pain relief and successful substitute for maintenance treatment in heroin and narcotic addiction. The aim of the study was to assess the trends of methadone-associated deaths in Tehran, Iran, in 2009-2015, from a forensic toxicology point of view. All methadone-associated deaths during this 7-year study period were evaluated according to demographic parameters and forensic toxicology analysis results. Results showed that 1274 cases of methadone-associated deaths were investigated during the study period. The incidence rate of methadone-associated deaths had risen 7.7 times in 2015 in comparison with 2009 (p < 0.05). The majority of cases were men (90.35%), aged from 20 to 40 years. About 80% of cases had shown positive results for other drugs and poisons in combination with methadone. Methamphetamine and tramadol were the most drugs detected in post-mortem samples. Death rates among methadone users in Tehran, Iran, increased year by year during 2009-2015. These findings raise the attention to the concomitant use of drugs with the need for changes in regulation and regulatory policy to restrict access and use of controlled drugs.

Opioid Prescribing Patterns and Patient Outcomes by Prescriber Type in the Oregon Prescription Drug Monitoring Program.

Objective: Prescription drug monitoring programs (PDMPs) were created to facilitate responsible use of controlled substances. In Oregon, physicians, physician's assistants (MDs/DOs/PAs), dentists, nurse practitioners (NPs), and naturopathic physicians (NDs) may prescribe opioids, but differences in prescribing practices, patient mix, and patient outcomes among prescriber types have not been characterized. Methods: De-identified Oregon PDMP data from October 2011 through October 2014 were linked with vital records and a statewide hospital discharge registry. The disciplines of registered prescribers were identified by board affiliations. Prescription profiles associated with opioid overdose risk were tabulated for patients with at least one registered prescriber. Opioid-related hospitalizations and deaths were identified using ICD-9 and ICD-10 codes. Results: There were 5,935 prescribers registered during the study period. Patients of NPs or NDs received more high-risk opioid prescriptions than patients of MDs/DOs/PAs. For example, they received greater proportions of high-dose prescriptions (NP 12.9%, ND 15%, MD/DO/PA 11.1%), and had greater opioid-related hospitalization (NP 1.7%, ND 3.1%, MD/DO/PA 1.2%; P < 0.005 for all). However, patients of NPs or NDs were also more likely to have four or more prescribers (NP 45.3%, ND 58.5%, MD/DO/PA 27.1%), and most of their patients' high-risk opioid prescriptions came from prescribers in other disciplines. Conclusion: Our analysis suggests significant differences in opioid prescription profiles and opioid-related hospitalization and mortality among patients receiving opioid prescriptions from nurse practitioners, naturopathic physicians, or medical clinicians in Oregon. However, these differences appear largely due to differences in patient mix between provider types rather than discipline-specific prescribing practices.

Developing an App by Exploiting Web-Based Mobile Technology to Inspect Controlled Substances in Patient Care Units.

We selected iOS in this study as the App operation system, Objective-C as the programming language, and Oracle as the database to develop an App to inspect controlled substances in patient care units. Using a web-enabled smartphone, pharmacist inspection can be performed on site and the inspection result can be directly recorded into HIS through the Internet, so human error of data translation can be minimized and the work efficiency and data processing can be improved. This system not only is fast and convenient compared to the conventional paperwork, but also provides data security and accuracy. In addition, there are several features to increase inspecting quality: (1) accuracy of drug appearance, (2) foolproof mechanism to avoid input errors or miss, (3) automatic data conversion without human judgments, (4) online alarm of expiry date, and (5) instant inspection result to show not meted items. This study has successfully turned paper-based medication inspection into inspection using a web-based mobile device.

Colour quantitation for chemical spot tests for a controlled substances presumptive test database.

Crime scene investigators (CSIs) often encounter unknown powders, capsules, tablets, and liquids at crime scenes, many of which are controlled substances. Because most drugs are white powders, however, visual determination of the chemical identity is difficult. Colourimetric tests are a well-established method of presumptive drug identification. Positive tests are often reported differently, however, because two analysts may perceive colour or record colourimetric results in different ways. In addition to perceiving colour differently, it is very common for there to be poor visibility conditions (e.g. rain, darkness) while performing these tests, further obscuring the results. In order to address these concerns and to create uniformity in the reporting of on-site colourimetric test results, this study has evaluated two of the state-of-the-art apps (ColorAssist® and Colorimeter®) for reporting the colour test results quantitatively in red-green-blue (RGB) format. The compiled library database of presumptive test results contains over 3300 data points including over 800 unique drug/test combinations. Variations observed between test replicates, from performing a test on different days, recording with a different device type (e.g. iPod Touch, iPhone models 4, 5c, 5s, or 6), and using different quantities of drug are discussed. Overall, the least variation in Euclidian norm was observed using ColorAssist® with the camera light (25.1±22.1) while the variation between replicates and data recorded using different devices was similar. The resulting library is uploaded to a smartphone application aimed to aid in identifying and interpreting suspected controlled substance evidence. Copyright © 2016 John Wiley & Sons, Ltd.

Controlled Substance Lock-In Programs: Examining An Unintended Consequence Of A Prescription Drug Abuse Policy.

Controlled substance lock-in programs are garnering increased attention from payers and policy makers seeking to combat the epidemic of opioid misuse. These programs require high-risk patients to visit a single prescriber and pharmacy for coverage of controlled substance medication services. Despite high prevalence of the programs in Medicaid, we know little about their effects on patients' behavior and outcomes aside from reducing controlled substance-related claims. Our study was the first rigorous investigation of lock-in programs' effects on out-of-pocket controlled substance prescription fills, which circumvent the programs' restrictions and mitigate their potential public health benefits. We linked claims data and prescription drug monitoring program data for the period 2009-12 for 1,647 enrollees in North Carolina Medicaid's lock-in program and found that enrollment was associated with a roughly fourfold increase in the likelihood and frequency of out-of-pocket controlled substance prescription fills. This finding illuminates weaknesses of lock-in programs and highlights the need for further scrutiny of the appropriate role, optimal design, and potential unintended consequences of the programs as tools to prevent opioid abuse.

Ultrafast capillary electrophoresis/mass spectrometry of controlled substances with optical isomer separation in about a minute.

RATIONALE: Analysis of forensic evidence by information-rich technologies such as mass spectrometry (MS) is one of the fastest growing areas in forensic analysis. To provide more accurate identification of forensic evidence, in the past few years there has been a growing interest in moving this technology to the field for on-site, real-time analysis. To this end, several portable mass spectrometers have been introduced; however, the analysis of controlled substances could be complicated by the existence of various isomers including optical isomers in which sentencing may depend on the identification of the isomer. To date very few portable separation devices are capable of separating and identifying the optical isomers. METHODS: In this study, the application of the portable ultrafast capillary electrophoresis (UFCE) to the separation of controlled substances is presented and the results are compared with the results obtained from a bench-top CE system. Both a nominal mass ion trap mass spectrometer and an accurate mass orbitrap mass spectrometer were interfaced with CE using a porous tip capillary. RESULTS: A mixture of several controlled substances can be separated and detected using UFCE/MS in about a minute using field strengths of ≥1000 V/cm. Furthermore, separation and detection of underivatized optical isomers of amphetamine, cathinone, nor-mephedrone, and pregabalin using UFCE/MS can be achieved with an analysis time of less than two minutes. Resolutions of 1.3, 3.7 and 3.8 were achieved for pregabalin, cathinone and nor-mephedrone, respectively, under UFCE/MS conditions. CONCLUSIONS: Amphetamine, cathinone, nor-mephedrone and pregabalin were separated and detected in about a minute, demonstrating the utility of the portable CE instrument for the analysis of controlled substances and their optical isomers. Copyright © 2016 John Wiley & Sons, Ltd.

High temperature mass detection using a carbon nanotube bilayer modified quartz crystal microbalance as a GC detector.

A small, portable gas chromatograph (GC) was assembled for the trace detection of controlled substances using a novel quartz crystal microbalance sensor (QCM). The QCM crystal surface was modified with a variety of sorption materials to increase adsorption thereby amplifying mass detection. Single polymer thin film coatings increased the QCM response by 1-2 orders of magnitude, while operating at over 100 °C. Adding a layer of carbonaceous nanomaterial (graphene or carbon nanotubes) above such a film dramatically increased sensitivity by up to 3 orders of magnitude compared to uncoated crystals. Separation and detection of submicrogram quantities of controlled substances was carried out within minutes by employing a GC column and detector temperature ramp up to 220 °C. An additional 10-fold enhancement in sensitivity was achieved by mechanical abrasion of the sample swabs used in the sample introduction process. This study demonstrated a novel use of a polymer composite modified QCM as a chemical sensor at high temperatures.

Investigation into the functionality of controlled drug denaturing/destruction kits.

CONTEXT: Throughout the UK a large amount of unwanted, expired or patient returned controlled drugs are disposed of every day, in community and hospital pharmacies, veterinary surgeries, hospices, private hospitals and industrial settings. This is mostly achieved through the use of commercially available controlled drug destruction/denaturing kits, but what do these kits actually do to the drug within them? OBJECTIVE: The primary aim of this study was to investigate the effect of six commercially available kits on morphine, a chosen model controlled drug. The secondary aim was to establish if the kits could be adapted to chemically destroy any drug disposed within it. MATERIALS AND METHODS: Morphine was dispensed in to six commercially available controlled drug destruction kits at a known concentration. The instructions on the kits were followed and after 48 h the amount of drug remaining was determined by HPLC. In addition a new kit containing sodium perborate was tested in the same way. RESULTS: Between 78 and 111% of the parent drug was found to still be present in the commercial kits tested after 48 h. In the sodium perborate 5% kit this level fell to 22%. DISCUSSION AND CONCLUSIONS: In conclusion all the commercially available CD denaturing kits tested do not destroy the controlled drug (morphine) tested but simply encapsulated it in gel. This means the parent form of the drug is still present and could potentially be recovered and abused. The new kit containing sodium perborate was much more effective in chemically destroying the parent drug but care must be taken in its use.

Prevalence and sunlight photolysis of controlled and chemotherapeutic drugs in aqueous environments.

This study addresses the occurrences and natural fates of chemotherapeutics and controlled drugs when found together in hospital effluents and surface waters. The results revealed the presence of 11 out of 16 drugs in hospital effluents, and the maximum detected concentrations were at the µg L(-1) level in the hospital effluents and the ng L(-1) level in surface waters. The highest concentrations corresponded to meperidine, morphine, 5-fluorouracil and cyclophosphamide. The sunlight photolysis of the target compounds was investigated, and the results indicated that morphine and codeine can be significantly attenuated, with half-lives of 0.27 and 2.5 h, respectively, in natural waters. Photolysis can lower the detected environmental concentrations, also lowering the estimated environmental risks of the target drugs to human health. Nevertheless, 5-fluorouracil and codeine were found to have a high risk quotient (RQ), demonstrating the high risks of directly releasing hospital wastewater into the environment.

Enantiomeric separations of illicit drugs and controlled substances using cyclofructan-based (LARIHC) and cyclobond I 2000 RSP HPLC chiral stationary phases.

Recently a novel class of chiral stationary phases (CSPs) based on cyclofructan (CF) has been developed. Cyclofructans are cyclic oligosaccharides that possess a crown ether core and pendent fructofuranose moieties. Herein, we evaluate the applicability of these novel CSPs for the enantiomeric separation of chiral illicit drugs and controlled substances directly without any derivatization. A set of 20 racemic compounds were used to evaluate these columns including 8 primary amines, 5 secondary amines, and 7 tertiary amines. Of the new cyclofructan-based LARIHC columns, 14 enantiomeric separations were obtained including 7 baseline and 7 partial separations. The LARIHC CF6-P column proved to be the most useful in separating illicit drugs and controlled substances accounting for 11 of the 14 optimized separations. The polar organic mode containing small amounts of methanol in acetonitrile was the most useful solvent system for the LARIHC CF6-P CSP. Furthermore, the LARIHC CF7-DMP CSP proved to be valuable for the separation of the tested chiral drugs resulting in four of the optimized enantiomeric separations, whereas the CF6-RN did not yield any optimum separations. The broad selectivity of the LARIHC CF7-DMP CSP is evident as it separated primary, secondary and tertiary amine containing chiral drugs. The compounds that were partially or un-separated using the cyclofructan based columns were screened with a Cyclobond I 2000 RSP column. This CSP provided three baseline and six partial separations.

Determination of drugs and drug-like compounds in different samples with direct analysis in real time mass spectrometry.

Direct analysis in real time (DART), a relatively new ionization source for mass spectrometry, ionizes small-molecule components from different kinds of samples without any sample preparation and chromatographic separation. The current paper reviews the published data available on the determination of drugs and drug-like compounds in different matrices with DART-MS, including identification and quantitation issues. Parameters that affect ionization efficiency and mass spectra composition are also discussed.