A proposed approach to confirm heroin administration - Regional differences in heroin purity is a major factor.

In forensic toxicology, a marker of street heroin use is urgent especially in the absence of urinary 6-monoacetylmorphine. ATM4G, the Glucuronide of Acetylated product of Thebaine compound 4 Metabolite (ATM4), arising from byproducts of street heroin synthesis has been considered as a useful marker in some European studies. However, whether ATM4G is a universal marker particularly in Southeast Asia due to 'street' heroin with high purity, it's still unclear. To investigate putative markers for different regions, ATM4G and other metabolites including the Acetylated product of Thebaine compound 3 Metabolite (ATM3) and thebaol, also originated from thebaine were detected in 552 urine samples from heroin users in Taiwan. Results were compared with that from samples collected in the UK and Germany. Only a sulfo-conjugate of ATM4, ATM4S, was detected in 28 Taiwanese users using a sensitive MS3 method whilst out of 351 samples from the UK and Germany, ATM4G was present in 91. Thebaol-glucuronide was first time detected in 118. No markers were detected in urine following herbal medicine use or poppy seed ingestion. The presence of ATM4S/ATM4G might be affected by ethnicities and heroin supplied in regions. Thebaol-glucuronide is another putative marker with ATM4G and ATM4S for street heroin use.

Using Urine Drug Testing to Estimate the Prevalence of Drug Use : Lessons Learned From the New York City Health and Nutrition Examination Survey, 2013-2014.

OBJECTIVES: Estimating the prevalence of drug use in the general population is important given its potential health consequences but is challenging. Self-reported surveys on drug use have inherent limitations that underestimate drug use. We evaluated the performance of linking urine drug testing with a local, representative health examination survey in estimating the prevalence of drug use in New York City (NYC). METHODS: We used urine drug testing from the NYC Health and Nutrition Examination Survey (NYC HANES) to estimate the prevalence of drug use (benzodiazepines, cocaine, heroin, and opioid analgesics) among the study sample and compare the findings with self-reported responses to questions about past-12-month drug use from the same survey. RESULTS: Of 1527 respondents to NYC HANES, urine drug testing was performed on 1297 (84.9%) participants who provided urine and consented to future studies. Self-reported responses gave past-12-month weighted estimates for heroin, cocaine, or any prescription drug misuse of 13.8% (95% CI, 11.6%-16.3%), for prescription drug misuse of 9.9% (95% CI, 8.1%-12.1%), and for heroin or cocaine use of 6.1% (95% CI, 4.7%-7.9%). Urine drug testing gave past-12-month weighted estimates for any drug use of 4.3% (95% CI, 3.0%-6.0%), for use of any prescription drug of 2.8% (95% CI, 1.9%-4.1%), and for heroin or cocaine use of 2.0% (95% CI, 1.2%-3.6%). CONCLUSION: Urine drug testing provided underestimates for the prevalence of drug use at a population level compared with self-report. Researchers should use other methods to estimate the prevalence of drug use on a population level.

Identification of characteristic heroin metabolites in urine based on data-mining technology and multivariate statistics analysis combined with a targeted verification approach for distinguishing heroin abusers.

A common phenomenon shows that ingestion of opium poppy shell-containing drugs can result in a "false-positive" urinalysis test result for mandatory or workplace heroin abuse screening. Owing to the short detection window (8 h in urine) of the characteristic heroin metabolite 6-monoacetylmorphine (6-MAM) confirmation or exclusion of heroin abusers still presents major challenges for toxicologists. In this work, we developed an ultra-performance liquid chromatography-time-of-flight mass spectrometry method (UPLC-TOF-MS) with online data acquisition and multiple post-data-mining technologies combined with a multivariate statistical and batch validation analysis workflow to assess the characteristic urine metabolites of heroin abusers. Based on the proposed methods, 28 characteristic metabolites were structurally identified, and their fragmentation patterns and metabolite pathways were also summarized. Correlation analysis was used to investigate the internal relationship and similarities among the identified metabolites, and seven representative metabolites were selected as "Target-metabolites". Multi-batch urine of samples of heroin abusers were certified based on the UPLC-MS/MS method for further validation of the practicability of using this method for routine analysis. Overall, the target-metabolites can be utilized as assistant "biomarkers" in workplace or mandatory drug screenings. This approach encourages further studies on the development of the "false-positive" identification system.

Effect of positive urine fentanyl screen on attitudes toward heroin use.

BACKGROUND: It is unknown if targeted risk reduction counseling in the health care setting, after documented exposure to fentanyl, can affect behavior change to reduce risks and increase utilization of evidence-based overdose prevention strategies. METHODS: We conducted a retrospective analysis of results (7/2018-6/2019) from questionnaire-facilitated counseling by recovery coaches in the emergency department (ED) and primary care settings following disclosure of a urine toxicology positive for fentanyl. RESULTS: Seventy-five percent of N = 101 respondents were neither aware of nor expecting fentanyl in their substances of use. Fifty-three (70 %) of those initially unaware answered that learning about exposure to and the risks from fentanyl changed their thoughts about reducing or abstaining from use. A greater proportion of patients seen in the ED expressed desire to stop or reduce opioid use as compared to ambulatory clinic patients (91 % vs. 46 %, p < 0.001). Of those not already engaged in treatment, 18 % and 15 % were interested in medication and behavioural health treatment, respectively, and each of them indicated a change in thought based on the counseling. Forty-five percent of individuals not yet receiving naloxone endorsed interest in receiving it, and 22 % of all respondents were somewhat or very interested in access to safe consumption sites. CONCLUSION: This study suggests a novel clinical utility in toxicology screens to inform behavior in the setting of illicit fentanyl exposure. In addition to linkages to evidence-based treatment, linkages to harm-mitigating strategies associated with ongoing substance use may be critical to a comprehensive overdose prevention strategy in the clinical setting.

The effects of extended-release injectable naltrexone and incentives for opiate abstinence in heroin-dependent adults in a model therapeutic workplace: A randomized trial.

AIM: To determine whether extended-release injectable naltrexone (XR-NTX), incentives for opiate abstinence, and their combination reduce opiate use compared to a usual care control and whether the combination reduces opiate use compared to either treatment alone. DESIGN: Randomized 2 × 2 single-site controlled trial conducted from November 2012 through May 2016. After a detoxification and oral naltrexone induction, participants were assigned to a Usual Care, Abstinence Incentives, XR-NTX, or XR-NTX plus Abstinence Incentives group for a six-month intervention period. SETTING: A model therapeutic workplace where participants could work on automated computer programs that targeted job-skills training for 4 h every weekday for 24 weeks and earn about $10 per hour. PARTICIPANTS: 84 heroin-dependent adults who were unemployed and medically approved for naltrexone. Most participants were male (71.4%), African American (80.1%), and cocaine dependent (71.4%). MEASUREMENTS: The primary outcome measure was the percentage of urine samples negative for opiates that were collected at once weekly assessments (24 per participant) that were not part of the intervention and for which participants were paid $10 for completing. INTERVENTION: Participants who attended the workplace provided thrice-weekly urine samples. Abstinence Incentives participants had to provide opiate-free urine samples to maintain maximum pay. XR-NTX participants received one injection every 4 weeks and were required to take injections in order to work and to maintain maximum pay. Usual Care participants were not offered XR-NTX and opiate urinalysis results did not affect pay. FINDINGS: A large percentage (65 of 149; 43.6%) of individuals failed the induction protocol required for randomization and to be eligible to receive XR-NTX. When missing urine samples were considered positive, there was no significant interaction between XR-NTX and Abstinence Incentives. XR-NTX plus Abstinence Incentives participants provided significantly more opiate-negative samples (81.3%, SD 39.0%) than XR-NTX participants (64.5%, SD 47.9%; aOR 10.4, 95% CI 1.3-85.5; P = .030). When urine samples were not replaced, there was a significant interaction between XR-NTX and Abstinence Incentives (aOR 77.0, 95% CI 1.3-4432;P = 0.036); XR-NTX plus Abstinence Incentives participants provided significantly more opiate-negative samples (99.6%, SD 0.1%) than XR-NTX participants (85.0%, SD 35.7%; aOR 147.6, 95% CI 6.3-3472; P = 0.002), Abstinence Incentives participants (91.9%, SD 27.3%; aOR 121.7, 95% CI 4.8-3067; P =0.004), and Usual Care participants (78.7%, SD 41.0%; aOR 233.4, 95% CI 9.4-5814; P <.001). No other group differences were significant. CONCLUSION: XR-NTX plus incentives for opiate abstinence increased opiate abstinence, but XR-NTX alone did not. XR-NTX can promote opiate abstinence when it is combined with incentives for opiate abstinence in a model therapeutic workplace.

Urine drug screening for early detection of unwitting use of fentanyl and its analogues among people who inject heroin in Sydney, Australia.

INTRODUCTION AND AIMS: North America has witnessed a dramatic rise in fatal opioid overdoses due to the unwitting consumption of non-pharmaceutical fentanyl and its analogues. While some of the drivers of this crisis-including profitability and access to high-potency opioids through internet sources-also apply in Australia, to our knowledge, there have been no ongoing surveillance studies of local populations. Therefore, this pilot study aimed to detect unintentional fentanyl consumption among people who inject heroin through instant urine screening, and determine the feasibility and acceptability of voluntary urinalysis of clients at the Medically Supervised Injecting Centre, Kings Cross, Sydney. DESIGN AND METHODS: Brief surveys and urine drug screens were conducted with 67 participants in Wave 1 (October 2017) and 51 participants in Wave 2 (March 2018). Urine samples were tested with BTNX Rapid Response™ fentanyl urine strip test at a detection level of 20 ng/mL norfentanyl. These strips also cross-react to numerous fentanyl analogues. RESULTS: There were no cases where positive urine tests suggested unwitting fentanyl use detected in this study. DISCUSSION AND CONCLUSIONS: These negative findings contrast sharply with similar Canadian studies. While no cases of fentanyl-laced heroin use have been detected so far, we have demonstrated that this surveillance design is low-cost, feasible and scalable approach to monitoring the considerable public-health threat of undetected fentanyl and its analogues in Australia. Further validation of cross-reactivity of test strips would strengthen this method.

Influence of social network on drug use among clients of methadone maintenance treatment centers in Kunming, China.

AIMS: To examine drug use behavior of clients attending Methadone Maintenance Treatment (MMT) programs and its relationship with the clients' social network characteristics. DESIGN: Cross-sectional study. SETTING: Four MMT clinics in Kunming, Yunnan province, China. PARTICIPANTS: 324 consecutive MMT clients. MEASUREMENTS: A structured, self-completed questionnaire on background characteristics and existing social network. Current drug use was assessed by urine test for opiate metabolites. ANALYSIS: The association between client's social network characteristics and their own current drug use behavior is analysed using multiple logistic regression adjusting for socio-demographic characteristics. Adjusted odds ratios (AOR) with 95% confidence intervals (CI) are obtained to give the strength of the associations. FINDINGS: MMT clients were more likely to concurrently use heroin while attending MMT if their social network had any of the following characteristics: more than half of the members were older than them (AOR = 1.03, 95% CI = 1.00,1.06), any member had a high level of influence on them (AOR = 6.47, 95% CI = 2.86,14.65) and any member joined them in using drugs (AOR = 1.94, 95% CI = 1.04,3.63). Having a social network member who could provide emotional support (AOR = 0.11, 95% CI = 0.03,0.35), having a spouse and/or child in their social network (AOR = 0.44, 95% CI = 0.24,0.81) and having a social network member with a high level of closeness (AOR = 0.28, 95% CI = 0.09,0.90) were associated with a decreased odds of heroin use. CONCLUSION: Social networks who could provide MMT clients with emotional support and a close relationship were significant factors for reducing the risk of concurrent drug use among clients attending MMT clinics in Kunming, China. Behavioral interventions should address the role of family and social network members in providing support to these clients.

Metabolites of Heroin in Several Different Post-mortem Matrices.

In some forensic autopsies blood is not available, and other matrices are sampled for toxicological analysis. The aims of the present study were to examine whether heroin metabolites can be detected in different post-mortem matrices, and investigate whether analyses in other matrices can give useful information about concentrations in peripheral blood. Effects of ethanol on the metabolism and distribution of heroin metabolites were also investigated. We included 45 forensic autopsies where morphine was detected in peripheral blood, concomitantly with 6-acetylmorphine (6-AM) detected in any matrix. Samples were collected from peripheral blood, cardiac blood, pericardial fluid, psoas muscle, lateral vastus muscle, vitreous humor and urine. Opioid analysis included 6-AM, morphine, codeine, and morphine glucuronides. The 6-AM was most often detected in urine (n = 39) and vitreous humor (n = 38). The median morphine concentration ratio relative to peripheral blood was 1.3 (range 0-3.6) for cardiac blood, 1.4 (range 0.07-5.3) for pericardial fluid, 1.2 (range 0-19.2) for psoas muscle, 1.1 (range 0-1.7) for lateral vastus muscle and 0.4 (range 0.2-3.2) for vitreous humor. The number of 6-AM positive cases was significantly higher (P = 0.03) in the ethanol positive group (n = 6; 86%) compared to the ethanol negative group (n = 14; 37%) in peripheral blood. The distribution of heroin metabolites to the different matrices was not significantly different between the ethanol positive and the ethanol negative group. This study shows that toxicological analyses of several matrices could be useful in heroin-related deaths. Urine and vitreous humor are superior for detection of 6-AM, while concentrations of morphine could be assessed from peripheral or cardiac blood, pericardial fluid, psoas muscle and lateral vastus muscle.

Predictors of induction onto extended-release naltrexone among unemployed heroin-dependent adults.

BACKGROUND AND AIM: Extended-release naltrexone (XR-NTX) blocks the effects of opioids for 4weeks; however, starting treatment can be challenging because it requires 7 to 10days of abstinence from all opioids. In the present study we identified patient and treatment characteristics that were associated with successful induction onto XR-NTX. METHODS: 144 unemployed heroin-dependent adults who had recently undergone opioid detoxification completed self-report measures and behavioral tasks before starting an outpatient XR-NTX induction procedure. Employment-based reinforcement was used to promote opioid abstinence and adherence to oral naltrexone during the induction. Participants were invited to attend a therapeutic workplace where they earned wages for completing jobs skills training. Participants who had used opioids recently were initially invited to attend the workplace for a 7-day washout period. Then those participants were required to provide opioid-negative urine samples and then take scheduled doses of oral naltrexone to work and earn wages. Participants who had not recently used opioids could begin oral naltrexone immediately. After stabilization on oral naltrexone, participants were eligible to receive XR-NTX and were randomized into one of four treatment groups, two of which were offered XR-NTX. Binary and multiple logistic regressions were used to identify characteristics at intake that were associated with successfully completing the XR-NTX induction. RESULTS: 58.3% of participants completed the XR-NTX induction. Those who could begin oral naltrexone immediately were more likely to complete the induction than those who could not (79.5% vs. 25.0%). Of 15 characteristics, 2 were independently associated with XR-NTX induction success: legal status and recent opioid detoxification type. Participants who were not on parole or probation (vs. on parole or probation) were more likely to complete the induction (OR [95% CI]=2.5 [1.1-5.7], p=0.034), as were those who had come from a longer-term detoxification program (≥21days) (vs. a shorter-term [<21days]) (OR [95% CI]=7.0 [3.0-16.6], p<0.001). CONCLUSIONS: Our analyses suggest that individuals recently leaving longer-term opioid detoxification programs are more likely to complete XR-NTX induction. Individuals on parole or probation are less likely to complete XR-NTX induction and may need additional supports or modifications to induction procedures to be successful.

Urinary Kinetics of Heroin Metabolites in Pigs Shortly After Intake.

In previous experimental studies on heroin metabolites excretion in urine, the first sample was often collected a few hours after intake. In forensic cases, it is sometimes questioned if a positive urine result is expected e.g., 30 min after intake. The aim of this study was to investigate urinary excretion of heroin metabolites (morphine, 6-monoacetylmorphine (6-MAM) and morphine-3-glucuronide (M3G)) every 30 min until 330 min after injection of a 20 mg heroin dose in six pigs. Samples were analyzed using a previously published, fully validated liquid chromatography-tandem mass spectrometry method. All metabolites were detected after 30 min in all pigs. The time to maximum concentration (Tmax) median (range) for 6-MAM and morphine was 30 min (first sample) (30-120), and 90 min (30-330) for M3G. In four of the six pigs, the Tmax of 6-MAM and morphine was reached within 30 min. All analytes were still detectable at the end of study. This study showed that positive results in urine are expected to be seen shortly after use of heroin in pigs. Detection times were longer than previously indicated, especially for 6-MAM, but previous studies used lower doses. As the physiology of these animals resembles that of the humans, transferability to man is expected.

Urinary excretion study following consumption of various poppy seed products and investigation of the new potential street heroin marker ATM4G.

Discrimination between street heroin consumption and poppy seed ingestion represents a major toxicological challenge in daily routine work. Several difficulties associated with conventional street heroin markers originate from their versatile occurrence in various poppy seed products and medications, respectively, as well as to small windows of detection. A novel opportunity to overcome these hindrances is represented by the new potential street heroin marker acetylated-thebaine-4-metabolite glucuronide (ATM4G), originating from thebaine during street heroin synthesis followed by metabolic reactions after administration. In this study, urine samples after consumption of different German poppy seed products and urine samples from subjects with suspicion of preceding heroin consumption were tested for ATM4G, 6-AC (6-acetylcodeine), papaverine, noscapine, 6-MAM (6-monoacetylmorphine), morphine, and codeine. Neither 6-AC and 6-MAM nor ATM4G but morphine and codeine could be detected in urine samples following poppy seed ingestion. As well, neither papaverine nor noscapine could be observed even after consumption of poppy seeds containing up to 37 µg noscapine and up to 9.8 µg papaverine, respectively. Concerning the urine samples with suspicion of preceding heroin consumption, ATM4G could be detected in 9 of 43 cases. By contrast, evidence of 6-AC and 6-MAM, respectively, could only be seen in 7 urine samples. In conclusion, ATM4G should be measured additionally in cases requiring discrimination of street heroin consumption from poppy seed intake. Copyright © 2016 John Wiley & Sons, Ltd.

Clinical and Forensic Diagnosis of Very Recent Heroin Intake by 6-acetylmorphine Immunoassay Test and LC-MS/MS Analysis in Urine and Blood.

AIM: The study evaluates the suitability of a specific immunoassay screening test for 6-acetylmorphine (6-AM) in the setting of suspected very recent heroin consumption for forensic and clinical purposes. MATERIAL AND METHOD: The EMIT® II Plus 6-AM immunoassay was applied in 65 cases that had already tested positive for morphine in urine or blood. Biological samples (n.65 urine and n.53 blood) were obtained from workplace drug tests (WDT n. 5), tests for driving under the influence of drugs (DUID n. 30), vehicle accidents (n. 10), overdoses (n. 12) and heroin-related deaths (n. 8) cases. The 6-AM screening assay results were confirmed with the LC-MS/MS analysis in relation to the cut-off set at 10 ng/mL for both urine and blood. RESULTS: Among the 65 urine samples (all morphine-positive), 38 samples were 6-AM-positive and 27 were 6-AM-negative with 100% agreement between the positive/negative results of the two assays. Among the 53 blood samples (34 positive and 19 negative for the morphine), 16 were 6-AM positive and 37 were negative. Only one of the blood samples, positive for 6-AM by LC-MS/MS at 10.3 ng/mL, was negative by the immunoassay test. Based on the concordance between the results of the 6-AM immunoassay versus the LC-MS/MS, the sensitivity of the 6-AM assay was calculated as 100% and 95% for urine and blood respectively, with a specificity and accuracy of 100% for both biological samples. In addition, the study demonstrated that the 6-AM assay test, originally developed for urine, is also sufficiently sensitive to identify 6-AM in blood. Therefore, it could be applied in cases of vehicle accidents or overdose to distinguish rapidly between very recent heroin use and the intake of other opiates for therapeutic purposes.

Aberrant default-mode functional and structural connectivity in heroin-dependent individuals.

BACKGROUND: Little is known about connectivity within the default mode network (DMN) in heroin-dependent individuals (HDIs). In the current study, diffusion-tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) were combined to investigate both structural and functional connectivity within the DMN in HDIs. METHODS: Fourteen HDIs and 14 controls participated in the study. Structural (path length, tracts count, (fractional anisotropy) FA and (mean diffusivity) MD derived from DTI tractography)and functional (temporal correlation coefficient derived from rs-fMRI) DMN connectivity changes were examined in HDIs. Pearson correlation analysis was performed to compare the structural/functional indices and duration of heroin use/Iowa gambling task(IGT) performance in HDIs. RESULTS: HDIs had lower FA and higher MD in the tract connecting the posterior cingulate cortex/precuneus (PCC/PCUN) to right parahippocampal gyrus (PHG), compared to the controls. HDIs also had decreased FA and track count in the tract connecting the PCC/PCUN and medial prefrontal cortex (MPFC), as well as decreased functional connectivity between the PCC/PCUN and bilateral PHG and MPFC, compared to controls. FA values for the tract connecting PCC/PCUN to the right PHG and connecting PCC/PCUN to the MPFC were negatively correlated to the duration of heroin use. The temporal correlation coefficients between the PCC/PCUN and the MPFC, and the FA values for the tract connecting the PCC/PCUN to the MPFC were positively correlated to IGT performance in HDIs. CONCLUSIONS: Structural and functional connectivity within the DMN are both disturbed in HDIs. This disturbance progresses as duration of heroin use increases and is related to deficits in decision making in HDIs.

Prevalence of heroin markers in urine for pain management patients.

Surveys of current trends indicate heroin abuse is associated with nonmedical use of pain relievers. Consequently, there is an interest in evaluating the presence of heroin-specific markers in chronic pain patients who are prescribed controlled substances. A total of 926,084 urine specimens from chronic pain patients were tested for heroin/diacetylmorphine (DAM), 6-acetylmorphine (6AM), 6-acetylcodeine (6AC), codeine (COD), and morphine (MOR). Heroin and markers were analyzed using liquid chromatography tandem mass spectrometry (LC-MS-MS). Opiates were analyzed following hydrolysis using LC-MS-MS. The prevalence of heroin use was 0.31%, as 2871 were positive for one or more heroin-specific markers including DAM, 6AM, or 6AC (a known contaminant of illicit heroin). Of these, 1884 were additionally tested for the following markers of illicit drug use: 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), methamphetamine (MAMP), 11-nor-9-carboxy-Δ(9)-tetracannabinol (THCCOOH), and benzoylecgonine (BZE); 654 (34.7%) had positive findings for one or more of these analytes. The overall prevalence of heroin markers were as follows: DAM 1203 (41.9%), 6AM 2570 (89.5%), 6AC 1082 (37.7%). MOR was present in 2194 (76.4%) and absent (

The poppy seed defense: a novel solution.

A major toxicological challenge is distinguishing whether morphine in urine, in the absence of 6-monoacetylmorphine (6-MAM), originates from 'street' heroin use or poppy seed ingestion. Manufacturing byproducts from the synthesis of illicit heroin include those that originate from the reaction of acetic anhydride with the alkaloid impurity, thebaine, which undergoes skeletal rearrangement, resulting in compounds with a 2-(N-methylacetamido)ethyl side-chain. The hypothesis that the tertiary amide in this side-chain is resistant to endogenous hydrolysis was supported from in-vitro experiments; a glucuronide metabolite (designated 'ATM4G') was identified that may be used as a marker of 'street' heroin administration. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis for this metabolite was then performed on selected urine specimens from 22 known heroin users, these being negative on routine testing for 6-MAM by gas chromatography-mass spectrometry (GC-MS), using the generally applied reporting threshold of 10 ng/mL, but positive for the presence of morphine. Peaks corresponding to the retention time for the metabolite marker were clearly observed for 16 of the 22 samples, with variations of the ratios of its three dependent ions being within ± 30% of that produced in vitro. Conversely, 6-MAM was detected in only 3 samples, but at concentrations <1 ng/mL. Such a high frequency for the presence of the metabolite marker in urine, in the absence of 6-MAM, is noteworthy and suggests that detection of this metabolite may offer an important advance in forensic toxicology, allowing the development of a new and more definitive test for heroin abuse and thus a potential solution to the so-called 'poppy seed defense'.

Distinguishing heroin abuse from codeine administration in the urine of Chinese people by UPLC-MS-MS.

Heroin is a highly addictive drug, and heroin abuse is considered to be a serious criminal act. The major metabolite of heroin, morphine, can usually be detected as evidence of heroin abuse. However, it is difficult to determine heroin use when morphine and codeine are both detected, because codeine use will also result in the presence of morphine in urine. Therefore, it is important to distinguish heroin abuse from codeine administration. In this study, urine samples from 21 volunteers with various ingestion patterns of a compound codeine phosphate oral solution were used as negative controls, and urine samples from 89 alleged heroin users were used as positive controls. Urine from single and multiple doses of codeine administration were collected at different time points for a systematic comparison. After protein precipitation, the urine samples were analyzed for the presence of free morphine, free codeine and their metabolites by ultra-performance liquid chromatography-tandem mass spectrometry. The method of percentiles, with median and standard interquartile ranges, was used to describe and analyze the data based on the normality of the distribution. The ratios of concentration of morphine and morphine to codeine were found to be the possible criteria to distinguish heroin users from codeine users in Chinese people.

Stability of pain-related medications, metabolites, and illicit substances in urine.

BACKGROUND: Effective urine drug testing requires an understanding of the stability of medications, metabolites and other substances excreted in the urine matrix. When the testing results do not fit the clinical picture, physicians frequently request repeat testing of the original specimen in order to corroborate the results. We determined the stability in urine of various medications, metabolites, and illicit substances commonly requested for testing by physicians treating patients with pain and pain-related disorders. METHODS: Quantitative analyses of urine specimens were performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Two replicates at a high and low concentration were analyzed at time 0, and after 2, 3 and 6 months following storage at +4 °C and -20 °C. At each time interval, the percent difference from time 0 for each analyte was calculated and averaged for each storage condition. RESULTS: For the majority of medications, the percent differences were within 20% of the original measurement for all 3 storage conditions. All were within 30% of the original measurement after 2, 3 and 6 months in all storage conditions, except for 7-amino-clonazepam, and carboxy-tetrahydrocannabinol. CONCLUSIONS: The findings from the current study confirm that the majority of medications, metabolites, and illicit substances commonly requested for testing by physicians treating patients with pain and pain-related disorders are stable within 20% of the original concentration when stored refrigerated or frozen for up to 6 months. Thus, delayed testing, repeat testing, and add-on testing of urine specimens can yield reliable results for up to 6 months following the urine collection date.

Retrospective study of outcomes, for patients admitted to a drug treatment centre board.

Retrospective study of urinary heroin outcomes of a cohort (123) of patients commenced on a methadone treatment program. Significantly poorer outcomes were associated with urines positive for cocaine (OR 0.69 CI 0.59-0.81) benzodiazepines (OR 0.7 CI 0.53-0.93) with prescribing of low dose methadone (OR 0.65 CI 0.48-0.87), with urines positive for heroin at time of admission (OR 0.74 CI 0.56-0.97) and with behavioural sanctions (OR 0.8, CI 0.65-0.98). Improved outcomes were associated with granting of take away methadone (OR 1.34 CI 1.1-1.62). with an indication of improved outcomes associated with alcohol positive urines (OR 1.34 CI 0.95-1.9) and increased duration of clinic attendance (OR 1.21 CI 0.99-1.47). On multiple regression analysis low dose methadone (0.07 CI 0.01-0.33) prescribing remained negatively associated with urine heroin outcomes.

Tetrodotoxin alleviates acute heroin withdrawal syndrome: a multicentre, randomized, double-blind, placebo-controlled study.

1. Tetrodotoxin (TTX) is a powerful sodium channel blocker extracted from the puffer fish. The efficacy and safety of TTX as monotherapy for the treatment of acute heroin withdrawal syndrome were evaluated in the present study. This 7-day, multicentre, randomized, double-blind, placebo-controlled study was carried out between December 2008 and October 2009. In total, 216 patients who met the Diagnostic and Statistical Manual of Mental Disorders IV diagnosis of heroin addiction were recruited. After providing written informed consent, subjects were randomly assigned to double-blind treatment in one of the following groups: 5 µg TTX group (group 1), 10 µg TTX group (group 2) or the placebo group (group 3). 2. Evidence suggests that both 5 and 10 µg TTX significantly reduced withdrawal symptoms by day 3 compared with placebo, and there was no significant difference in the incidence of adverse events in the three groups. 3. In conclusion, this clinical trial shows that TTX (5 and 10 µg given t.i.d.) is effective in alleviating opiate withdrawal symptoms with few side-effects.