-
Molecules (Basel, Switzerland) Oct 2022Common methodologies such as liquid-liquid extraction and solid-phase extraction are applied for the extraction of opioids from biological specimens i.e., blood and...
Common methodologies such as liquid-liquid extraction and solid-phase extraction are applied for the extraction of opioids from biological specimens i.e., blood and urine. Techniques including LC-MS/LC-MSMS, GC-MS, etc. are used for qualitative or quantitative determination of opioids. The goal of the present work is to design a green, economic, rugged, and simple extraction technique for famous opioids in human blood and urine and their simultaneous quantification by GC-MS equipped with an inert plus electron impact (EI) ionization source at SIM mode to produce reproducible and efficient results. Morphine, codeine, 6-acetylmorphine, nalbuphine, tramadol and dextromethorphan were selected as target opioids. Anhydrous Epsom salt was applied for dSPE of opioids from blood and urine into acetonitrile extraction solvent with the addition of sodium phosphate buffer (pH 6) and n-hexane was added to remove non-polar interfering species from samples. BSTFA was used as a derivatizing agent for GC-MS. Following method validation, the LOD/LLOQ and ULOQ were determined for morphine, codeine, nal-buphine, tramadol, and dextromethorphan at 10 ng/mL and 1500 ng/mL, respectively, while the LOD/LLOQ and ULOQ were determined for 6-acetylmorphine at 5 ng/mL and 150 ng/mL, respectively. This method was applied to real blood and urine samples of opioid abusers and the results were found to be reproducible with true quantification.
Topics: Acetonitriles; Analgesics, Opioid; Codeine; Dextromethorphan; Gas Chromatography-Mass Spectrometry; Humans; Morphine; Morphine Derivatives; Nalbuphine; Solid Phase Extraction; Solvents; Substance Abuse Detection; Tramadol
PubMed: 36235294
DOI: 10.3390/molecules27196761 -
Frontiers in Public Health 2022Impulsivity, affective instability, and neglect of oneself and other people's safety as symptoms of personality dysfunction are associated with risky behaviors regarding...
BACKGROUND
Impulsivity, affective instability, and neglect of oneself and other people's safety as symptoms of personality dysfunction are associated with risky behaviors regarding the transmission of infectious diseases either sexually or by intravenous drug abuse.
OBJECTIVE
The aim of this study was to analyze the association between hepatitis C virus (HCV) infection and personality dysfunction in opiate addicts on opioid substitution treatment.
METHODS
This was a cross-sectional, observational investigation of patients over 18 years of age who were actively participating in opioid substitution treatment at five centers in Bosnia and Herzegovina. The occurrence of HCV infection was the primary study outcome, and personality functioning, the main independent variable, was assessed using the Severity Indices of Personality Problems (SIPP-118) questionnaire. The association between scores of personality functioning domains items and HCV infection status was determined by binary logistic regression analysis.
RESULTS
Patients on opioid substitution therapy with HCV infection more frequently had personality disorders (OR 2.168, 95% CI 1.161-4.05) and were treated longer than patients without HCV infection (OR 1.076, 95% CI 1.015-1.14). HCV infection was associated with lower self-respect (OR 0.946, 95% CI 0.906-0.988), decreased capacity to have enduring relationships with other people (OR 0.878, 95% CI 0.797-0.966), and lower capability to cooperate with others (OR 0.933, 95%CI 0.888-0.98). On the other hand, except for self-respect, other elements of the Identity Integration domain (enjoyment, purposefulness, stable self-image, and self-reflexive functioning), when more functional, increased the risk of HCV infection.
CONCLUSIONS
Our study demonstrates that opiate addicts on opioid substitution treatment have a higher risk of HCV infection if their personality is dysfunctional, especially in the aspects of self-respect, enduring relationships, and cooperativity. The risk is even higher in addicts who have an established diagnosis of any kind of personality disorder.
Topics: Adolescent; Adult; Cross-Sectional Studies; Hepacivirus; Hepatitis C; Humans; Opiate Alkaloids; Opiate Substitution Treatment; Opioid-Related Disorders; Personality; Personality Disorders
PubMed: 36159261
DOI: 10.3389/fpubh.2022.1009413 -
Yakugaku Zasshi : Journal of the... 2023Sinomenine (SIN) is a major component contained in extracts of the Chinese medicinal herb Sinomenium acutum. SIN has various pharmacological properties, including...
Sinomenine (SIN) is a major component contained in extracts of the Chinese medicinal herb Sinomenium acutum. SIN has various pharmacological properties, including cytoprotection, immunosuppression and anti-inflammation effects. Furthermore, recent studies have reported that SIN has anti-tumor and antidepressant effects, which has created a strong need for SIN kinetic studies. This paper reports a simple and sensitive competitive enzyme-linked immunosorbent assay (ELISA) for the pharmacokinetic evaluation of SIN. Anti-SIN serum was obtained by immunizing mice with an antigen conjugated with bovine serum albumin and carboxylic modified SIN using the N-succinimidyl ester method. Enzyme labeling of SIN with horseradish peroxidase was similarly performed using carboxylic modified SIN. Under optimized conditions, this ELISA shows a linear detection range from 40 to 5000 pg/mL, and a limit of detection of 12.1 pg/mL for 50-µL samples. This assay was specific for SIN and showed very slight cross-reactivity with dextromethorphan (0.45%), dimemorfan (0.22%) and codeine (0.01%), but no cross-reactivity with 2-methoxycyclohex-2-enone (<0.001%). Using this ELISA, SIN levels were easily determined in the blood of mice after oral administration of Kampo medicine, Boiogito. The ELISA may be a valuable tool for studies of the biological and pharmacological properties of SIN.
Topics: Mice; Animals; Kinetics; Enzyme-Linked Immunosorbent Assay; Morphinans; Antigens
PubMed: 36724928
DOI: 10.1248/yakushi.22-00164 -
International Journal of Molecular... Aug 2020Opioids and their antagonists alter vitamin C metabolism. Morphine binds to glutathione (l-γ-glutamyl-l-cysteinyl-glycine), an intracellular ascorbic acid recycling...
Glutathione and Glutathione-Like Sequences of Opioid and Aminergic Receptors Bind Ascorbic Acid, Adrenergic and Opioid Drugs Mediating Antioxidant Function: Relevance for Anesthesia and Abuse.
Opioids and their antagonists alter vitamin C metabolism. Morphine binds to glutathione (l-γ-glutamyl-l-cysteinyl-glycine), an intracellular ascorbic acid recycling molecule with a wide range of additional activities. The morphine metabolite morphinone reacts with glutathione to form a covalent adduct that is then excreted in urine. Morphine also binds to adrenergic and histaminergic receptors in their extracellular loop regions, enhancing aminergic agonist activity. The first and second extracellular loops of adrenergic and histaminergic receptors are, like glutathione, characterized by the presence of cysteines and/or methionines, and recycle ascorbic acid with similar efficiency. Conversely, adrenergic drugs bind to extracellular loops of opioid receptors, enhancing their activity. These observations suggest functional interactions among opioids and amines, their receptors, and glutathione. We therefore explored the relative binding affinities of ascorbic acid, dehydroascorbic acid, opioid and adrenergic compounds, as well as various control compounds, to glutathione and glutathione-like peptides derived from the extracellular loop regions of the human beta 2-adrenergic, dopamine D1, histamine H1, and mu opioid receptors, as well as controls. Some cysteine-containing peptides derived from these receptors do bind ascorbic acid and/or dehydroascorbic acid and the same peptides generally bind opioid compounds. Glutathione binds not only morphine but also naloxone, methadone, and methionine enkephalin. Some adrenergic drugs also bind to glutathione and glutathione-like receptor regions. These sets of interactions provide a novel basis for understanding some ways that adrenergic, opioid and antioxidant systems interact during anesthesia and drug abuse and may have utility for understanding drug interactions.
Topics: Analgesics, Opioid; Ascorbic Acid; Dehydroascorbic Acid; Enkephalin, Methionine; Glutathione; Humans; Hydromorphone; Methadone; Morphine; Naloxone; Peptides; Receptors, Adrenergic, beta-2; Receptors, Dopamine D1; Receptors, Histamine H1; Receptors, Opioid; Receptors, Opioid, mu
PubMed: 32872204
DOI: 10.3390/ijms21176230 -
Epidemiologic Reviews Jan 2020The volatile opioid epidemic is associated with higher levels of opioid use disorder (OUD) and negative health outcomes in adolescents and young adults. Medications for...
The volatile opioid epidemic is associated with higher levels of opioid use disorder (OUD) and negative health outcomes in adolescents and young adults. Medications for opioid use disorder (MOUD) demonstrate the best evidence for treating OUD. Adherence to and retention in MOUD, defined as continuous engagement in treatment, among adolescents and young adults, however, is incompletely understood. We examined the state of the literature regarding the association of age with adherence to and retention in MOUD using methadone, buprenorphine, or naltrexone among persons aged 10-24 years, along with related facilitators and barriers. All studies of MOUD were searched for that examined adherence, retention, or related concepts as an outcome variable and included adolescents or young adults. Search criteria generated 10,229 records; after removing duplicates and screening titles and abstracts, 587 studies were identified for full-text review. Ultimately, 52 articles met inclusion criteria for abstraction and 17 were selected for qualitative coding and analysis. Younger age was consistently associated with shorter retention, although the overall quality of included studies was low. Several factors at the individual, interpersonal, and institutional levels, such as concurrent substance use, MOUD adherence, family conflict, and MOUD dosage and flexibility, appeared to have roles in MOUD retention among adolescents and young adults. Ways MOUD providers can tailor treatment to increase retention of adolescents and young adults are highlighted, as is the need for more research explaining MOUD adherence and retention disparities in this age group.
Topics: Adolescent; Buprenorphine; Child; Humans; Methadone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Young Adult
PubMed: 32239206
DOI: 10.1093/epirev/mxaa001 -
The Journal of Pharmacology and... Aug 2020δ-Opioid receptor (-receptor) agonists produce antihyperalgesia, antidepressant-like effects, and convulsions in animals. However, the role of agonist efficacy in...
δ-Opioid receptor (-receptor) agonists produce antihyperalgesia, antidepressant-like effects, and convulsions in animals. However, the role of agonist efficacy in generating different -receptor-mediated behaviors has not been thoroughly investigated. To this end, efficacy requirements for -receptor-mediated antihyperalgesia, antidepressant-like effects, and convulsions were evaluated by comparing the effects of the partial agonist BU48 and the full agonist SNC80 and changes in the potency of SNC80 after -receptor elimination. Antihyperalgesia was measured in a nitroglycerin-induced thermal hyperalgesia assay. An antidepressant-like effect was evaluated in the forced swim test. Mice were observed for convulsions after treatment with SNC80 or the -opioid receptor partial agonist BU48. Ligand-induced G protein activation was measured by [S]guanosine 5'-O-[-thio]triphosphate binding in mouse forebrain tissue, and -receptor number was measured by [H]D-Pen-enkephalin saturation binding. BU48 produced antidepressant-like effects and convulsions but antagonized SNC80-induced antihyperalgesia and G protein activation. The potency of SNC80 was shifted to the right in -receptor heterozygous knockout mice and naltrindole-5'-isothiocyanate-treated mice, and the magnitude of potency shift differed across assays, with the largest shift occurring in the thermal hyperalgesia assay, followed by the forced swim test and then convulsion observation. Naltrindole antagonized these SNC80-induced behaviors with similar potencies, suggesting that these effects are mediated by the same type of -receptor. These data suggest that -receptor-mediated behaviors display a rank order of efficacy requirement, with antihyperalgesia having the highest requirement, followed by antidepressant-like effects and then convulsions. These findings further our understanding of the pharmacological mechanisms mediating the in vivo effects of -opioid receptor agonists. SIGNIFICANCE STATEMENT: -Opioid receptor (δ-receptor) agonists produce antihyperalgesia, antidepressant-like effects, and convulsions in animal models. This study evaluates pharmacological properties, specifically the role of agonist efficacy and receptor reserve, underlying these δ-receptor-mediated behaviors. These data suggest that δ-receptor-mediated behaviors display a rank order of efficacy requirement, with antihyperalgesia having the highest requirement, followed by antidepressant-like effects and then convulsions.
Topics: Animals; Behavior, Animal; Benzamides; Buprenorphine; Drug Partial Agonism; Mice; Naltrexone; Piperazines; Receptors, Opioid, delta
PubMed: 32467352
DOI: 10.1124/jpet.119.262717 -
The American Journal of Drug and... Jan 2023Accurate drug use identification through subjective self-report and toxicological biosample (hair) analysis are necessary to determine substance use sequelae in youth....
Accurate drug use identification through subjective self-report and toxicological biosample (hair) analysis are necessary to determine substance use sequelae in youth. Yet consistency between self-reported substance use and robust, toxicological analysis in a large sample of youth is understudied. We aim to assess concordance between self-reported substance use and hair toxicological analysis in community-based adolescents. Hair results by LC-MS/MS and GC-MS/MS and self-reported past-year substance use from an Adolescent Brain Cognitive Development (ABCD) Study subsample ( = 1,390; ages 9-13; 48% female) were compared. The participants were selected for hair selection through two methods: high scores on a substance risk algorithm selected 93%; 7% were low-risk, randomly selected participants. Kappa coefficients the examined concordance between self-report and hair results. 10% of youth self-reported any past-year substance use (e.g. alcohol, cannabis, nicotine, and opiates), while a mostly non-overlapping 10% had hair results indicating recent substance use (cannabis, alcohol, non-prescription amphetamines, cocaine, nicotine, opiates, and fentanyl). In randomly selected low-risk cases, 7% were confirmed positive in hair. Combining methods, 19% of the sample self-reported substance use and/or had a positive hair sample. Kappa coefficient of concordance between self-report and hair results was low (kappa = 0.07; = .007). Hair toxicology identified substance use in high-risk and low-risk ABCD cohort subsamples. Given low concordance between hair results and self-report, reliance on either method alone would incorrectly categorize 9% as non-users. Multiple methods for characterizing substance use history in youth improves accuracy. Larger representative samples are needed to assess the prevalence of substance use in youth.
Topics: Humans; Adolescent; Female; Child; Male; Self Report; Hair Analysis; Nicotine; Tandem Mass Spectrometry; Chromatography, Liquid; Substance Abuse Detection; Substance-Related Disorders; Opiate Alkaloids
PubMed: 36812240
DOI: 10.1080/00952990.2023.2164931 -
American Journal of Veterinary Research Jan 2023To investigate the cytotoxic effects of 2 different concentrations of buprenorphine and compare them with bupivacaine and morphine on healthy equine chondrocytes in...
OBJECTIVE
To investigate the cytotoxic effects of 2 different concentrations of buprenorphine and compare them with bupivacaine and morphine on healthy equine chondrocytes in vitro.
SAMPLE
Primary cultured equine articular chondrocytes from 3 healthy adult horses.
PROCEDURES
Chondrocytes were exposed for 0 and 2 hours to the following treatments: media (CON; negative control); bupivacaine at 2.2 mg/mL (BUPI; positive control); morphine at 2.85 mg/mL (MOR); buprenorphine at 0.12 mg/mL (HBUPRE); or buprenorphine at 0.05 mg/mL (LBUPRE). Chondrocyte viability was assessed using live/dead staining, water-soluble tetrazolium salt-8 (WST-8) cytotoxic assay, LDH assay, and flow cytometry. All continuous variables were evaluated with a mixed ANOVA with treatment, time, and their interactions as the fixed effects and each horse as the random effect.
RESULTS
Buprenorphine showed a concentration-dependent chondrotoxic effect. The viability of chondrocytes was significantly decreased with exposure to HBUPRE and BUPI compared to CON, MOR, and LBUPRE.
CLINICAL RELEVANCE
Negligible chondrotoxic effects were observed in healthy cultured equine chondrocytes exposed to 0.05 mg/mL of buprenorphine, whereas higher concentrations (0.12 mg/mL) showed a marked cytotoxic effect. Based on these results, low concentrations of buprenorphine appear to be safe for intra-articular administration. Further evaluation of this dose in vivo is needed before recommending its clinical use.
Topics: Horses; Animals; Chondrocytes; Anesthetics, Local; Buprenorphine; Bupivacaine; Antineoplastic Agents; Morphine Derivatives; Cartilage, Articular
PubMed: 36662607
DOI: 10.2460/ajvr.22.08.0143 -
The International Journal on Drug Policy Mar 2022Buprenorphine-naloxone (BUP-NX) is a first-line treatment for opioid use disorder and has a superior safety profile compared to other forms of opioid agonist therapy. In...
BACKGROUND
Buprenorphine-naloxone (BUP-NX) is a first-line treatment for opioid use disorder and has a superior safety profile compared to other forms of opioid agonist therapy. In Canada, restrictions on BUP-NX prescribing were relaxed in 2016, which may have had an effect on rates of diversion and non-prescribed use. We sought to longitudinally examine the reported availability and use of non-prescribed BUP-NX among people who use drugs (PWUD) in an urban Canadian setting.
METHODS
We collected data from two linked prospective cohorts of PWUD in Vancouver, Canada, and examined self-reported availability and use of non-prescribed BUP-NX over time. We used a multivariable generalized estimating equations model to identify trends and factors associated with the immediate availability (i.e., within 10 min) of non-prescribed BUP-NX.
RESULTS
Among 1617 participants between 2014 and 2020, the immediate availability of non-prescribed BUP-NX increased from 16% to 63% (p<0.001). In the multivariable analysis, factors independently associated with immediate BUP-NX availability included calendar year (adjusted odds ratio = 1.19, 95% confidence interval: 1.15-1.23), along with a number of other variables suggestive of more severe substance use disorders. Only 17 participants ever reported use of non-prescribed BUP-NX.
CONCLUSIONS
We observed that BUP-NX has become increasingly available in the unregulated drug supply in recent years but its use has remained infrequent in this setting. These results suggest that relaxed restrictions on BUP-NX prescribing have not been a major driver of increased non-prescribed use in this population.
Topics: Buprenorphine; Buprenorphine, Naloxone Drug Combination; Canada; Humans; Naloxone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Prospective Studies
PubMed: 34875527
DOI: 10.1016/j.drugpo.2021.103545 -
Pharmacological Reports : PR 2012Aim of the study was to assess dihydrocodeine (DHC) and metabolites concentrations and their correlations with DHC analgesia in cancer patients with pain. Thirty... (Clinical Trial)
Clinical Trial
Aim of the study was to assess dihydrocodeine (DHC) and metabolites concentrations and their correlations with DHC analgesia in cancer patients with pain. Thirty opioid-naive patients with nociceptive pain intensity assessed by VAS (visual analogue scale) > 40 received controlled-release DHC as the first (15 patients, 7 days) or as the second opioid (15 patients, 7 days). Blood samples were taken on day 2, 4 and 7 at each study period. DHC and its metabolites were assayed by HPLC. DHC provided satisfactory analgesia when administered as the first or the second opioid superior to that of tramadol. When DHC was the first opioid administered, DHC and dihydrocodeine-6-glucuronide (DHC-6-G) concentrations increased in the second and the third comparing to the first assay. A trend of nordihydromorphine (NDHM) level fall between the first and the third assay was noted; trends of dihydromorphine (DHM) level increase in the second relative to the first determination and decrease in the third compared to the second assay were observed. When DHC followed tramadol treatment a trend of DHC concentration increase in the second relative to the first assay was noted. DHC-6-G level increased in the second and in the third comparing to the first determination; NDHM and DHM concentrations were stable. DHC and DHC-6-G concentrations increased similarly during both treatment periods which suggest their prominent role in DHC analgesia. Few significant correlations were found between DHC dose, DHC and metabolites serum concentrations with analgesia suggesting the individual DHC dose titration.
Topics: Aged; Aged, 80 and over; Analgesia; Analgesics, Opioid; Codeine; Dihydromorphine; Female; Humans; Male; Middle Aged; Neoplasms; Nociceptive Pain; Pain Management; Pain Measurement
PubMed: 22580524
DOI: 10.1016/s1734-1140(12)70734-x