RESUMEN
A facile electrochemical approach is proposed for the synchronous determination of acetaminophen (ACP), codeine (COD) and caffeine (CAF) utilizing unmodified screen-printed electrodes (SPEs). The determination of ACP, COD and CAF has been explored across different supporting electrolytes including sulfuric acid (H2SO4), hydrochloric acid (HCl), phosphoric acid (H3PO4) and Briton Robinson (B.R) buffer solutions. It was found that a 0.05 mol L-1 sulfuric acid solution is an optimal supporting electrolyte utilized for voltammetric analysis of ACP, COD, and CAF with improved sensitivity, stability, and reproducibility. The electro-analytical sensing of ACP, COD and CAF was investigated using SPEs within linear concentration ranges of 3.0-35.0 µmol L-1, 10-160 µmol L-1 and 10-160 µmol L-1 and revealed competitively low limits of detection (3S/N) of 0.9, 4.8 and 6.3 µmol L-1 for ACP, COD and CAF, respectively. The results indicated the possibility of such a simple and quick electroanalytical protocol for online monitoring of pharmaceutical formulations comprising ACP, COD, and CAF drugs in human fluids with satisfactory recovery.
Asunto(s)
Acetaminofén , Cafeína , Codeína , Técnicas Electroquímicas , Electrodos , Grafito , Acetaminofén/análisis , Acetaminofén/química , Codeína/análisis , Codeína/química , Cafeína/análisis , Cafeína/química , Humanos , Grafito/química , Técnicas Electroquímicas/métodos , Límite de Detección , Reproducibilidad de los ResultadosRESUMEN
The analytical determination of opiates in biological samples is a critical mission and remains a challenge for almost all judicial and clinical drug testing panels due to their high abuse potential. Based on the high sensitivity of the longitudinal surface plasmon resonance (LSPR) peak of gold nanorods (AuNRs), we successfully developed a novel and simple refractive index sensing platform for detection of morphine (MOR) and codeine (COD) by means of 2-amino-5-mercapto-1,3,4-thiadiazole functionalized gold nanorods (AMTD-AuNRs) in aqueous solution, which is, to the best of our knowledge, the first report on the assay of MOR and COD using AuNRs. AMTD molecules strongly anchor onto the tips of AuNRs via the mercapto group and subsequent hydrogen-bonding interactions between AMTD and the analytes induced end-to-end chain assembly of AuNRs and a consequent decrease of the LSPR absorption band at 850 nm along with a bathochromic shift and emergence of a new hybridized plasmon mode at 1050 nm which was characterized using a Vis-NIR spectrophotometer. After systematic optimization, the absorbance ratio (A1050/A850) was proportional to the concentration of MOR in the ranges of 0.08-5 µM and 0.2-8 µM for COD without any significant effect from possible interferents. Furthermore, detection limits of 40 and 62 nM were achieved for MOR and COD, respectively, which are much lower than the cut-off level of 2000 ng mL-1 for opiates in urine samples set by the Substance and Abuse Mental Health Services Administration (SAMHSA). Eventually, as proof-of-applicability, human urine and blood serum samples spiked with MOR and COD were analyzed and excellent recoveries ranging from 94.4 to 108.9% were obtained, demonstrating the successful applicability of the designed refractive index probe in real biological specimens.
Asunto(s)
Codeína , Oro , Morfina , Nanotubos , Resonancia por Plasmón de Superficie , Codeína/orina , Codeína/sangre , Codeína/análisis , Oro/química , Nanotubos/química , Morfina/orina , Morfina/sangre , Humanos , Resonancia por Plasmón de Superficie/métodos , Técnicas Biosensibles/métodos , Límite de Detección , Espectroscopía Infrarroja Corta/métodosRESUMEN
It is a new approach to identify legal or illegal use of morphine through information on municipal wastewater. However, the sources of morphine in wastewater are complex, and distinguishing the contribution of different sources has become a key issue. A total of 262 influent samples from 61 representative wastewater treatment plants in a typical city were collected from October 2022 to March 2023. The concentrations of morphine, codeine, thebaine, papaverine, noscapine, and monoacetylmorphine were analyzed in wastewater and poppy straws. Combined with the proportion of alkaloids in poppy straws, the source analysis of alkaloids in wastewater was analyzed using the ratio method and positive matrix factorization model (PMF). Only five alkaloids were detected in wastewater, and monoacetylmorphine, a metabolite of heroin, was not detected. The concentrations of morphine and codeine were significantly higher than those of noscapine, papaverine, and thebaine. By constructing the ratios of codeine/(morphine + codeine) and noscapine/(noscapine + codeine), the source of poppy straw could be qualitatively distinguished. The PMF results showed that three sources of morphine for medical use, poppy straw, and codeine contributed 44.9%, 43.7%, and 9.4%, respectively. The different sources varied in these months due to the COVID-19 and influenza A outbreaks, in which the use of drugs containing poppy straws and codeine was the main source, whereas the use of morphine analgesics remained relatively stable. Inventory analysis further demonstrated the reliability of the source contributions from the PMF model, and morphine was not abused in this city.
Asunto(s)
Alcaloides , Noscapina , Papaver , Morfina/análisis , Aguas Residuales , Papaverina/análisis , Tebaína/análisis , Noscapina/análisis , Reproducibilidad de los Resultados , Codeína/análisis , Derivados de la Morfina/análisis , Alcaloides/análisisRESUMEN
Codeine is a common analgesic drug that is a pro-drug of morphine. It also has a high risk of abuse as a recreational drug because of its extensive distribution as an OTC drug. Therefore, sensitive and selective screening methods for codeine are crucial in forensic analytical chemistry. To date, a commercial analytical kit has not been developed for dedicated codeine determination, and there is a need for an analytical method to quantify codeine in the field. In the present work, potential modulation was combined with electrochemiluminescence (ECL) for sensitive determination of codeine. The potential modulated technique involved applying a signal to electrodes by superimposing an AC potential on the DC potential. When tris(2,2'-bipyridine)ruthenium(II) ([Ru(bpy)3]2+) was used as an ECL emitter, ECL activity was confirmed for codeine. A detailed investigation of the electrochemical reaction mechanism suggested a characteristic ECL reaction mechanism involving electrochemical oxidation of the opioid framework. Besides the usual ECL reaction derived from the amine framework, selective detection of codeine was possible under the measurement conditions, with clear luminescence observed in an acidic solution. The sensitivity of codeine detection by potential modulated-ECL was one order of magnitude higher than that obtained with the conventional potential sweep method. The proposed method was applied to codeine determination in actual prescription medications and OTC drug samples. Codeine was selectively determined from other compounds in medications and showed good linearity with a low detection limit (150 ng mL-1).
Asunto(s)
Analgésicos Opioides , Codeína , Aminas , Analgésicos Opioides/análisis , Analgésicos Opioides/química , Codeína/análisis , Codeína/química , Electrodos , Medicamentos sin Prescripción , LuminiscenciaRESUMEN
Insects on corpses could be a useful tool for the detection of exogenous substances such as drugs of abuse. The identification of exogenous substances in carrion insects is critical for proper estimation of the postmortem interval. It also provides information about the deceased person that may prove useful for forensic purposes. High-performance liquid chromatography coupled with Fourier transform mass spectrometry is a highly sensitive analytical technique that can identify substances even at very low concentrations, such as in the case of searching for exogenous substances in larvae. In this paper, a method is proposed for the identification of morphine, codeine, methadone, 6-monoacetylmorphine (6-MAM) and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in the larvae of Lucilia sericata, a common carrion fly widely distributed in temperate areas of the world. The larvae, which were reared on a pig meat substrate, were killed once they reached their third stage by immersion in hot water at 80 °C and aliquoted into 400 mg samples. The samples were fortified with 5 ng of morphine, methadone and codeine. After solid-phase extraction, the samples were processed with a liquid chromatograph coupled to a Fourier transform mass spectrometer. This qualitative method has been validated and tested on larvae from a real case. The results lead to the correct identification of morphine, codeine, methadone and their metabolites. This method could prove useful in cases where toxicological analysis must be conducted on highly decomposed human remains, where biological matrices are very limited. Furthermore, it could help the forensic pathologist to better estimate the time of death, as the growth cycle of carrion insects can undergo changes if exogenous substances are taken.
Asunto(s)
Dípteros , Metadona , Animales , Humanos , Metadona/análisis , Metadona/química , Metadona/metabolismo , Analgésicos Opioides , Codeína/análisis , Morfina/análisis , Larva/metabolismo , Cromatografía Líquida de Alta Presión/métodos , Derivados de la Morfina , Dípteros/químicaRESUMEN
Keratinized matrices, including nails, are among the most resistant matrices that can be analyzed in cases where remains are deeply decomposed and relatively non-invasive for living people. In order to exploit these new matrices in the search for exogenous substances, it is necessary to develop analytical technologies capable of achieving high levels of sensitivity. In this technical note, an easy method is presented for the simultaneous extraction and quantification of three narcotic substances (morphine, codeine and methadone), two benzodiazepines (BDZs) (clonazepam and alprazolam) and an antipsychotic (quetiapine) from nail matrix by analysis in ultra-high-performance liquid chromatography at high-resolution mass spectrometry. The method has been validated following the Standard Practices for Method Validation in Forensic Toxicology of the Scientific Working Group for Forensic Toxicology. Nail specimens from eight authentic postmortem (PM) cases and 13 living donor samples were extracted and analyzed. Of the eight PM samples, five resulted positive for at least one of the three substances searched. Ten of the 13 living donor specimens were positive for at least one of the targeted BDZs or quetiapine.
Asunto(s)
Alprazolam , Codeína , Humanos , Cromatografía Líquida de Alta Presión/métodos , Codeína/análisis , Alprazolam/análisis , Clonazepam , Morfina/análisis , Fumarato de Quetiapina/análisis , Metadona/análisis , Uñas/química , Benzodiazepinas/análisisRESUMEN
Objective: To estimate the consumption level of four drugs in Beijing using wastewater-based epidemiology (WBE). Methods: The primary sludge from one large wastewater treatment plants (WWTPs) was collected in Beijing from July 2020 to February 2021. The concentrations of codeine, methadone, ketamine and morphine in the sludge were detected through solid-phase extraction-liquid chromatography-tandem mass spectrometry. The consumption, prevalence and number of users of four drugs were estimated by using the WBE approach. Results: Among 416 sludge samples, codeine had the highest detection rate (82.93%, n=345) with a concentration [M (Q1, Q3)] of 0.40 (0.22-0.8) ng·g-1, and morphine had the lowest detection rate (28.37%,n=118) with a concentration [M (Q1, Q3)] of 0.13 (0.09, 0.17) ng·g-1. There was no significant difference in the consumption of the four drugs on working days and weekends (all P values>0.05). Drug consumption was significantly higher in winter than that in summer and autumn (all P values <0.05). The consumption [M (Q1, Q3)] of codeine, methadone, ketamine and morphine in winter was 24.9 (15.58, 38.6), 9.39 (4.57, 26.72), 9.84 (5.18, 19.45) and 5.67 (3.57, 13.77) µg·inhabitant-1·day-1, respectively. For these drugs, there was an upward trend in the average drug consumption during summer, autumn and winter (the Z values of the trend test were 3.23, 3.16, 2.19, and 3.32, respectively and all P values<0.05). The prevalence [M (Q1, Q3)] of codeine, methadone, ketamine and morphine were 0.0056% (0.003 4%, 0.009 2%), 0.0148% (0.009 6%, 0.026 7%),0.0333% (0.0210%, 0.0710%) and 0.0072% (0.003 8%, 0.011 7%), respectively. The estimated number of drug users [M (Q1, Q3)] was 918 (549, 1 511), 2 429 (1 578, 4 383), 5 451 (3 444, 11 642) and 1 173 (626, 1 925),respectively. Conclusion: Codeine, methadone, ketamine and morphine have been detected in the sludge of WWTPs in Beijing, and the consumption level of these drugs varies in different seasons.
Asunto(s)
Ketamina , Contaminantes Químicos del Agua , Humanos , Beijing , Monitoreo Epidemiológico Basado en Aguas Residuales , Aguas del Alcantarillado/análisis , Aguas Residuales , Ketamina/análisis , Codeína/análisis , Metadona/uso terapéutico , Metadona/análisis , Contaminantes Químicos del Agua/análisisRESUMEN
Fingerprints are invisible traces that result from a deposition of sweat and sebum present on the papillary ridges. As sweat and sebum contain drugs, fingerprints are promising since collection is rapid, non-invasive and difficult to falsify. Very limited data are available in the literature, and therefore, it seems opportune to study the transfer of xenobiotics onto the items taken in hand via the fingerprints. Two studies were implemented using the ballpoint pen as a model. The objective of the first study was to compare the nicotine concentrations found on the pens of three smokers and three non-smokers. Five pens, belonging to each subject and used regularly, were rubbed with a cotton swab dipped in methanol and analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). The second study was to analyze the transfer via fingerprints of four volunteers, after administration of 30 mg of codeine. The objective was to determine the feasibility of this study and the time corresponding to the highest concentration of codeine. Over a 24-h period, new pens were handled for 5 min by the four volunteers, rubbed with a cotton swab dipped in methanol, and then analyzed by LC-MS-MS. The nicotine study showed a major difference between the nicotine concentrations obtained from smokers (between 6 and 276 ng/pen) and non-smokers (between 2 and 4 ng/pen). After administration of 30 mg of codeine, the analysis of the pens of the four volunteers allowed to demonstrate the presence of codeine up to 24 h between 9 and 544 pg/pen. Normal hygiene practices did not influence the final result. The highest concentration was observed after 2 h. Morphine was also detected (between 19 and 33 pg/pen). These preliminary results should be considered a demonstration of the interest of fingerprints testing to document drug exposure.
Asunto(s)
Metanol , Xenobióticos , Humanos , Nicotina , Codeína/análisis , Espectrometría de Masas en Tándem/métodos , Detección de Abuso de Sustancias/métodosRESUMEN
Objective: To estimate the consumption level of four drugs in Beijing using wastewater-based epidemiology (WBE). Methods: The primary sludge from one large wastewater treatment plants (WWTPs) was collected in Beijing from July 2020 to February 2021. The concentrations of codeine, methadone, ketamine and morphine in the sludge were detected through solid-phase extraction-liquid chromatography-tandem mass spectrometry. The consumption, prevalence and number of users of four drugs were estimated by using the WBE approach. Results: Among 416 sludge samples, codeine had the highest detection rate (82.93%, n=345) with a concentration [M (Q1, Q3)] of 0.40 (0.22-0.8) ng·g-1, and morphine had the lowest detection rate (28.37%,n=118) with a concentration [M (Q1, Q3)] of 0.13 (0.09, 0.17) ng·g-1. There was no significant difference in the consumption of the four drugs on working days and weekends (all P values>0.05). Drug consumption was significantly higher in winter than that in summer and autumn (all P values <0.05). The consumption [M (Q1, Q3)] of codeine, methadone, ketamine and morphine in winter was 24.9 (15.58, 38.6), 9.39 (4.57, 26.72), 9.84 (5.18, 19.45) and 5.67 (3.57, 13.77) μg·inhabitant-1·day-1, respectively. For these drugs, there was an upward trend in the average drug consumption during summer, autumn and winter (the Z values of the trend test were 3.23, 3.16, 2.19, and 3.32, respectively and all P values<0.05). The prevalence [M (Q1, Q3)] of codeine, methadone, ketamine and morphine were 0.0056% (0.003 4%, 0.009 2%), 0.0148% (0.009 6%, 0.026 7%),0.0333% (0.0210%, 0.0710%) and 0.0072% (0.003 8%, 0.011 7%), respectively. The estimated number of drug users [M (Q1, Q3)] was 918 (549, 1 511), 2 429 (1 578, 4 383), 5 451 (3 444, 11 642) and 1 173 (626, 1 925),respectively. Conclusion: Codeine, methadone, ketamine and morphine have been detected in the sludge of WWTPs in Beijing, and the consumption level of these drugs varies in different seasons.
Asunto(s)
Humanos , Beijing , Monitoreo Epidemiológico Basado en Aguas Residuales , Aguas del Alcantarillado/análisis , Aguas Residuales , Ketamina/análisis , Codeína/análisis , Metadona/análisis , Contaminantes Químicos del Agua/análisisRESUMEN
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.
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Nalbufina , Tramadol , Acetonitrilos , Analgésicos Opioides , Codeína/análisis , Dextrometorfano , Cromatografía de Gases y Espectrometría de Masas/métodos , Humanos , Morfina/análisis , Derivados de la Morfina/orina , Extracción en Fase Sólida/métodos , Solventes , Detección de Abuso de Sustancias/métodosRESUMEN
In this study, magnetic pomelo peel-derived biochar composite was fabricated and applied as a low-cost adsorbent for the simultaneous extraction of morphine-like opioids named morphine, codeine, and 6-monoacetylmorphine from wastewaters, prior to their determination via liquid chromatography-mass spectrometry. A total of four biochar products were synthesized under different pyrolytic temperatures of 400, 500, 600, and 700°C, respectively, and the 400°C biochar was found to have the greatest extraction ability, with enrichment factors of 34, 58, and 61 for the three drugs. The primary adsorption mechanism includes π-π interaction and H-bonding. Parameters affecting the extraction of opioids were optimized. Under optimum conditions (such as pH = 7; adsorbent amount = 15 mg; sample volume = 20 ml; eluent solvent, 200 µl of methanol), the method was proved to be linear in the range of 0.05-10.0 µg/L, with coefficients of determination greater than 0.99, and the limits of detection were 0.006-0.010 µg/L. In-batch and inter-batch precisions were 1.8%-6.5% and 4.8%-10.6%, respectively. The method was successfully applied to the determination of the target opioids in the samples of influent and effluent wastewater. The developed method by using magnetic pomelo peel-derived biochar could potentially be applied for the effective estimation of illicit drug consumption.
Asunto(s)
Aguas Residuales , Contaminantes Químicos del Agua , Aguas Residuales/análisis , Analgésicos Opioides , Contaminantes Químicos del Agua/análisis , Cromatografía Liquida/métodos , Espectrometría de Masas , Codeína/análisis , Fenómenos Magnéticos , Extracción en Fase Sólida/métodos , Cromatografía Líquida de Alta Presión/métodosRESUMEN
Wastewater-based epidemiology (WBE) was applied to estimate illicit drugs consumption at a provincial scale in southwest China. A large-scale wastewater sampling campaign was carried out from October to November in 2021 in 156 different wastewater treatment plants (WWTPs). Two 24-h composite influent wastewater samples were collected in each WWTP. Concentrations of 11 illicit drugs or their metabolites were determined using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Benzoylecgonine, cocaine, 6-monoacetylmorphine, norketamine, 3,4-methylenedioxymethamphetamine (MDMA), and MDA were not detected in any of the wastewater samples. Methamphetamine and morphine were detected in >84% of samples, while ketamine was found in about 6% of the samples. The city-specific population-weighted consumption of methamphetamine and ketamine were in the range of 0.6-49.7 and N.D.-7.0 mg 1000 inh-1 day-1, respectively, with provincial population-weighted values of 22.6 and 2.4 mg 1000 inh-1 day-1 in southwest China. The city-specific load of morphine varied from 3.2 to 10.2 mg 1000 inh-1 day-1, with provincial population-weighted load of 6.7 mg 1000 inh-1 day-1. Taking into account therapeutic use of morphine and codeine, the provincial heroin consumption was estimated to be 10.3 mg 1000 inh-1 day-1, ranging from 1.7 to 18.5 mg 1000 inh-1 day-1 in 21 cities. Overall, the patterns of illicit drugs use were similar across southwest China, with high prevalence of methamphetamine and heroin, but relatively low use of ketamine. These findings could provide accurate drugs consumption information for timely identifying potential hotspots of illicit drugs use in southwest China.
Asunto(s)
Cocaína , Drogas Ilícitas , Ketamina , Metanfetamina , N-Metil-3,4-metilenodioxianfetamina , Contaminantes Químicos del Agua , China/epidemiología , Cromatografía Liquida , Ciudades , Cocaína/análisis , Codeína/análisis , Heroína/análisis , Drogas Ilícitas/análisis , Metanfetamina/análisis , Morfina/análisis , Detección de Abuso de Sustancias/métodos , Espectrometría de Masas en Tándem , Aguas Residuales/química , Contaminantes Químicos del Agua/análisisRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Papaveris Pericarpium, which is the dried husk of Papaver somniferum L., has been used as a phytomedicine to relieve cough, diarrhea and pain. The alkaloid codeine contained therein via biotransformation converts to morphine and potentially produces addictive and toxic effects. Due to the healthy concern for a pregnant woman, our hypothesis is that codeine and its metabolites can penetrate the placental barrier to reach the foetus and amniotic fluid, and these processes may be modulated by the transporter. AIM OF THE STUDY: Because codeine is also considered a prodrug of morphine, it has a good analgesic effect. It is often used by pregnant women but may expose the foetus to the risk of morphine harm. The aim of this study is to investigate the metabolic rate, distribution and transplacental transfer mechanism of codeine and its metabolites morphine and morphine-3-glucuronide (M3G) in pregnant rats and to assess the risk of medication for pregnant women. MATERIALS AND METHODS: Ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) combined with a microdialysis system was developed to monitor codeine, morphine and M3G in multiple sites of maternal blood, placenta, foetus and amniotic fluid after codeine administration. A compartmental model was used to calculate the pharmacokinetic parameters of codeine in blood after codeine administration (10 mg/kg, i.v.). The area under the concentration (AUC) ratio of AUCmetabolite/AUCcodeine and AUCtissue/AUCblood was used to represent the metabolic biotransformation ratio and the drug from blood-to-tissue transfer ratio, respectively. RESULTS: The pharmacokinetic results demonstrated that codeine fit well with a two-compartment model and went through rapid metabolism to morphine and M3G in pregnant rats after codeine administration (10 mg/kg, i.v.). The biotransformation ratios of AUCmorphine/AUCcodeine, AUCM3G/AUCmorphine and AUCM3G/AUCcodeine were 0.12 ± 0.03, 54.45 ± 20.61 and 6.53 ± 2.47, respectively, after codeine administration (10 mg/kg, i.v.), which suggested that codeine was easily metabolized into M3G through morphine. The tissue distribution results demonstrated that all of the analytes penetrated into the foetus through the placenta; however, the blood-to-tissue transfer ratio (AUCtissue/AUCblood) of morphine and M3G was relatively lower than that of codeine after codeine administration (10 mg/kg, i.v.), which suggested that the blood-placenta barrier blocks the penetration of morphine and M3G into the foetus. Thus, the tissue transfer of morphine in the placenta and foetus was significantly enhanced by treatment with corticosterone, an inhibitor of organic cation transporter (OCT). CONCLUSION: Based on microdialysis coupled to a validated UHPLC-MS/MS system, the pharmacokinetics and metabolic biotransformation of codeine and its metabolites were analyzed and clarified. The potential mechanism of morphine placental transfer was modulated by OCT transporters.
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Codeína , Papaver , Animales , Codeína/análisis , Femenino , Humanos , Morfina , Derivados de la Morfina/análisis , Derivados de la Morfina/metabolismo , Placenta/química , Placenta/metabolismo , Embarazo , Ratas , Espectrometría de Masas en TándemRESUMEN
Active pharmaceutical ingredient (API) contamination of water sources, including opioid contamination, has become more common in recent years. Although drinking water-treatment plants help mitigate API infiltration, API contamination remains in some drinking water sources. Therefore, the ability to detect APIs at ultratrace concentrations is vital to ensure safe drinking water. A method for the ultratrace determination of fentanyl, hydrocodone, and codeine in drinking water via direct injection and high-performance liquid-chromatography tandem mass spectrometry (HPLC-MS/MS) was developed and validated. Drinking water samples (10 ml) are simply syringe-filtered and then analyzed by HPLC-MS/MS. A wide linear range (0.25-100 ng/L) and ultratrace limits of detection (80, 150, and 500 pg/L for fentanyl, hydrocodone, and codeine, respectively) were features of the method. The method produced excellent aggregate accuracies of 90%-115% and precisions of ≤11% for the three analytes tested. This method was used to test drinking water samples from 53 US locations, with hydrocodone and codeine detected in approximately 40% of the samples tested at concentrations between 0.3 and 20 ng/L. Codeine was detected at higher concentrations than hydrocodone (up to 7.3 times) for each sample containing these APIs. Fentanyl was not detected in any field drinking water sample. The detection of opioids in a large fraction of the US drinking water samples tested is cause for concern, and these levels should continue to be monitored to ensure that they do not become a threat to human health. Environ Toxicol Chem 2022;41:2658-2666. © 2022 SETAC.
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Agua Potable , Humanos , Agua Potable/química , Cromatografía Líquida de Alta Presión , Analgésicos Opioides/análisis , Espectrometría de Masas en Tándem/métodos , Hidrocodona/análisis , Cromatografía Liquida/métodos , Prevalencia , Codeína/análisis , Preparaciones FarmacéuticasRESUMEN
BACKGROUND: Dihydrocodeine (DHC) is considered a 'weak' opioid, but there is evidence of its increasing misuse in overdose deaths. This research aims to analyse trends in DHC-related deaths in England relevant to source and dose of DHC, and decedent demographics. METHODS: Cases from England reported to the National Programme on Substance Abuse Deaths (NPSAD) where DHC was identified at post-mortem and/or implicated in death between 2001 and 2020 were extracted for analysis. RESULTS: 2071 DHC-related deaths were identified. The greatest number of deaths involved illicitly obtained DHC and a significant increase in these deaths was recorded over time (r = 0.5, p = 0.03). However, there was a concurrent decline in the implication rate of DHC in causing death (r = -0.6, p < 0.01). Fatalities were primarily due to accidental overdose (64.8%) and misuse was highly prevalent in combination with additional central nervous system depressants (95.3%), namely illicit heroin/morphine and diazepam. In contrast, when DHC was obtained over-the-counter (OTC) suicide mortality accounted for almost half of the deaths (42.5%). Differences in polysubstance use were also identified, with less heroin/morphine and benzodiazepine co-detection, but increased OTC codeine co-detection. CONCLUSIONS: DHC misuse in England is increasing. The pharmacological consideration of DHC as a 'weak' opioid may be misinterpreted by users, leading to accidental overdosing. There is an urgent need to understand increasing polypharmacy in overdose deaths. Additionally, suicides involving DHC is a potential cause for concern and a review of OTC opioid-paracetamol preparations is necessary to determine whether the benefits of these medications continue to outweigh the risks of intentional overdose.
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Sobredosis de Droga , Trastornos Relacionados con Sustancias , Suicidio , Analgésicos Opioides/efectos adversos , Codeína/efectos adversos , Codeína/análogos & derivados , Codeína/análisis , Inglaterra/epidemiología , Heroína , Humanos , Morfina , Trastornos Relacionados con Sustancias/tratamiento farmacológicoRESUMEN
The forensic analysis of stable isotopes is a valuable tool to geo-source natural or semisynthetic drugs such as cocaine and heroin. The present study describes a novel methodology to isolate morphine from opium for isotopic analysis. Furthermore, this isotopic data from regional sources is corroborated with morphine data obtained from seized heroin (deacetylated to morphine) from the same regions. All five primary alkaloids of opium, namely, morphine, codeine, thebaine, noscapine, and papaverine, were quantified using high performance liquid chromatography with photodiode array (PDA) detector before the preparative experiment to gather a complete major alkaloidal profile. Morphine fractions of authentic opium submissions from Mexico, South America, Southwest Asia, and Southeast Asia were isolated and collected using preparative high performance liquid chromatography, and the collected morphine samples were subsequently analyzed by isotope ratio mass spectrometry. Carbon and nitrogen isotope data are presented. The data demonstrate that nitrogen ratios are capable of differentiating samples from Mexico and South America while carbon ratios are able to distinguish Southwest Asian samples from other source regions. Analogous results have routinely been observed (as part of Heroin Signature Program analysis) for morphine obtained from deacetylated authentic heroin samples from the same source regions. The results suggest that the poppy growing region has a greater influence on the carbon and nitrogen isotope values than the heroin manufacturing processes employed. When utilized in conjunction with existing signature methodologies, carbon and nitrogen isotope ratio data can enhance the ability to geo-source heroin.
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Morfina , Opio , Carbono , Codeína/análisis , Heroína/análisis , Isótopos de Nitrógeno/análisis , Opio/químicaRESUMEN
Considering that the use of psychoactive substances (PSs) is a risk factor to either higher intensity or frequency of suicidal behavior, hair analysis was conducted to investigate the most consumed PSs (opiates, amphetamine stimulants, marijuana, cocaine and heroin) in patients who attempted suicide and received urgent care at emergency service. Hair samples were extracted using methanol and sonicated under heating and then analyzed using liquid chromatography-tandem mass spectrometry. During validation, the method complied with international recommended criteria, with limits of detection between 0.0025 and 0.05 ng/mg and linearity between 0.1 and 4 ng/mg for methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), morphine, amphetamine, 6-acetylmorphine, 3,4-methylenedioxyamphetamine (MDA), fenproporex, diethylpropion and codeine; between 0.025 and 1 ng/mg for tetrahydrocannabinol (THC), benzoylecgonine and cocaethylene and between 0.25 and 10 ng/mg for cocaine and mazindol. A total of 109 hair samples were analyzed and segmented in 404 parts. Among all analyzed samples, 30.3% were positive for at least one PS (n = 33), such as cocaine (90.9%), codeine (12.1%), morphine (3.0%), MDMA (3.0%) and THC (3.0%). In segmental analysis of cocaine positive samples (n = 30), 76.7% of the samples indicated recent exposure to cocaine (<1 month). This same behavior was observed when analyzing codeine (n = 4) and morphine (n = 1). THC positive samples indicated exposure dated â¼4 months prior. In conclusion, the method was validated following international recommendations for the 12 most consumed PSs in Brazil, as well as two of the most common found metabolites.
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Cocaína , N-Metil-3,4-metilenodioxianfetamina , Anfetaminas/análisis , Cromatografía Liquida/métodos , Cocaína/análisis , Codeína/análisis , Dronabinol/análisis , Cabello/química , Humanos , Morfina/análisis , Derivados de la Morfina/análisis , N-Metil-3,4-metilenodioxianfetamina/análisis , Detección de Abuso de Sustancias/métodos , Intento de Suicidio , Espectrometría de Masas en Tándem/métodosRESUMEN
With tightening enforcement and restrictions amid the opioid epidemic, poppy seed tea is consumed as an alternative to mitigate the withdrawal symptoms or as a home remedy to relieve pain and stress. Previously published studies suggested the potential danger of consuming tea brewed with a moderate to a large amount of poppy seed. In this study, the effects of small quantity and repeat brewing on opiate concentrations were evaluated. A dispersive-micro solid phase extraction facilitated by magnetic carbon nanotubes (Mag-CNTs/d-µSPE) was developed, optimized, successfully validated, and applied to ten poppy seed tea samples using gas chromatography-mass spectrometry (GC-MS) analysis. A total of ten poppy seed samples were evaluated in this work. Two grams of bulk poppy seeds were brewed with 6 mL of heated and acidified DI water three times. The brewed tea samples were subjected to the validated Mag-CNTs/d-µSPE/GC-MS analysis. The total mean opiate concentrations obtained from three brews were 1.1-1926, 20.2-311, and 9.0-100 mg/kg for morphine, codeine, and thebaine, respectively. The total opiate yields obtained from the small quantity brewing, i.e., 6 g seed in 18 mL tea, in this study may provide minimal analgesic and euphoric effects. Over 80% of the total opiate yield was extracted in the first brew with acidified deionized water from the 10 min brewing period, and opiate yields from the second and third brew were minimal. However, potential overdose could occur for some tea samples when scaled up to the starter quantity of seed suggested for new users.
Asunto(s)
Nanotubos de Carbono , Papaver , Analgésicos Opioides , Codeína/análisis , Cromatografía de Gases y Espectrometría de Masas , Fenómenos Magnéticos , Morfina/análisis , Extracción en Fase Sólida , Té , Tebaína , AguaRESUMEN
Cocaine is a naturally occurring psychostimulant drug available worldwide. Drug trafficking networks adulterate pure cocaine with cutting agents to increase their earnings. This study presents a descriptive statistical analysis of the cutting agents found in 2118 cocaine samples that were seized in the Northern Region of Colombia (in the period 2015-2017). The data used in this study was drawn from the GC-MS analytical reports of the National Institute of Legal Medicine and Forensic Sciences -Colombia, Northern Region. Results showed diverse cutting agents in seized cocaine samples, from which the most commonly used are caffeine, phenacetin, lidocaine, imidazole and levamisole. In addition, cocaine samples showed different mixtures of the above cutting agents, predominantly caffeine/phenacetin and caffeine/lidocaine/phenacetin mixtures.
Asunto(s)
Cocaína/química , Contaminación de Medicamentos , Tráfico de Drogas/tendencias , Aporfinas/análisis , Cafeína/análisis , Codeína/análisis , Colombia , Humanos , Imidazoles/análisis , Levamisol/análisis , Lidocaína/análisis , Fenacetina/análisis , Análisis Espacio-Temporal , Tetramisol/análisisRESUMEN
The purpose of this investigation was to establish a mathematical model for determining the dissolution of diclofenac sodium and codeine phosphate simultaneously. Based on the dual-wavelength isosbestic point spectrophotometry, the dissolution of diclofenac sodium and codeine phosphate tablets was determined using Fiber-Optic Dissolution Test (FODT) instrument capable of real-time measurement. Dissolution curves showed that the dissolution process of diclofenac sodium was similar to that of codeine phosphate. The dissolution profile of diclofenac sodium and codeine phosphate at 45 min was concordant with that stated in Chinese pharmacopoeia. There was no significant difference between results obtained from FODT and HPLC (p>0.05). A fibre-optic dissolution test system assisted by the mathematical separation model of linear equations was able to detect the dissolution of diclofenac sodium and codeine phosphate simultaneously. The dissolution profiles and overall data, which can directly reflect the dissolution speed at each time point, can provide the basis for establishing standards for the quality evaluation of drugs.