Codeine Research Articles

Experimental, Modeling and Molecular Dynamics Simulation of Codeine Phosphate Dissolution in N-Methyl-2-pyrrolidone + Ethanol

Background: There is only limited data for solubility of codeine phosphate in binary systems available, which comes with uncertainties about the prediction accuracy of common thermodynamic models. Methods: This study investigated the codeine phosphate dissolution in N-methyl-2-pyrrolidone(NMP) and ethanol system using shake-flask method and mathematically described generated data by different thermodynamic models. The density as another property was also determined and fitted to the results of the Jouyban-Acree equation. The mean relative deviations were obtained to confirm the model’s accuracy. Moreover, ΔHº, ΔSº, and ΔGº of the dissolution of codeine phosphate in the NMP and ethanol system were calculated using the desired equations at Thm. Results: The dissolution process of codeine phosphate was identified as endotherm, the solubility in the binary mixtures was best at higher mass fractions of NMP and finally, the model predictions were deemed as excellent based on a mean relative deviation that was generally below eight percent. Conclusion: The results of this study could expand the available solubility database for codeine phosphate.

Evaluation of Antitussive, Expectorant and Analgesic Activities of Aqueous Extracts of Di-herbal Formulation of Whole Plant of Euphobia hirta and Lactuca virosa Leaf on Rodents

Euphorbia hirta and lactuca virosa are used to treat various ailment traditionally. This study aims at evaluating the antitussive, expectorant and analgesic effects of aqueous extracts of di-herbal formulation of Euphobia hirta and Lactuca virosa leaf. Citric acid induced, ammonia induced cough and phenol red dye secretion models were used. Hot plate and acetic acid induced writhing were used for analgesia. Combined 100mg/kg Euphorbia hirta and 50mg/kg lactuca virosa, 100mg/kg Euphorbia hirta and 100mg/kg lactuca virosa, 100mg/kg lactuca virosa only and 25 mg/kg of codeine phosphate reduces the number of cough bouts in the citric acid induced cough (P<0.05) compared to control. Combined 50mg/kg Euphorbia hirta and 100mg/kg lactuca virosa,100mg/kg Euphorbia hirta, 100mg/kg lactuca virosa and codeine phosphate reduces the number of cough bouts in the ammonia induced cough (P<0.001; P<0.0001) compared to the control. Combined 50mg/kg Euphorbia hirta and 100mg/kg lactuca virosa, 100mg/kg Euphorbia hirta and 50mg/kg lactuca virosa, 100mg/kg Euphorbia hirta and 100mg/kg lactuca virosa and 15mg/kg of Bromo-hexane increases the secretion of dye (P<0.0001; p<0.05) compared to control in phenol red dye secretion in mice. 100mg/kg Euphorbia hirta and 50mg/kg lactuca virosa,100mg/kg of Euphorbia hirta and 100mg/kg lactuca virosa and 3mg/kg Pentazocin increases the latency of pain threshold of mice (P<0.05). All the doses of the extract including 3mg/kg pentazocin increases the latency to pain threshold in the mice (P<0.001) after 2 hours. All the doses of the extract including aspirin reduces number of writhing (P<0.01). Euphorbia hirta and lactuca virosa has antitussive, expectorant and analgesic properties.

Modulatory effects of Cannabis sativa co-administration with tramadol and codeine on cognitive function in male rats

Most teenagers mix up various psychoactive cocktail substances in combinations to get intoxicated. The role of the mixture combination of codeine (CDE), tramadol (TMD), and Cannabis sativa (CNB) on brain cognition, purinergic, cholinergic, and antioxidant enzyme activities remains unknown. This study sought to assess the mechanism of action of combinations of CDE+ TMD+ CNB on the function and activities of the brain of male Wistar rats. Forty-eight male Wistar rats were divided into 8 groups, n = 6. Group 1 served as a control, groups 2, 3, and 4 were exposed to CDE (2 mg/kg bw), TMD (10 mg/kg bw), and CNB (200 mg/kg bw), while groups 5, 6, 7, and 8 were co-administered with CDE+TMD, CNB+ TMD, CNB+CDE, and CNB+TMD+CDE orally for 28 days. This study revealed the effect of prolonged administration of CNB, TMD, and CDE on the suppression of cognitive function, acetyl-cholinesterase (AChE), butyl-cholinesterase (BChE), monoamine oxidase (MAO) enzyme activities, and antioxidant enzyme activities in rats’ brains when compared against control rats (P < 0.05). However, the activities of ectonucleosides (NTPdase), adenosine deaminase (ADA), and malondialdehyde levels produced in the brain of rats were significantly elevated (P < 0.05). This study reported the mechanism behind the neurotoxicity of CNB, TMD, and CDE on rats’ cognitive, cholinergic, purinergic, and antioxidant enzymes as a consequence of the drastic reduction in cholinesterase enzyme activities leading to neurotransmitter poisoning.

Study analgesic effects of basil extracts (Ocimum basilicum L.) on mice

Objectives: To study analgesic effects of basil extracts (Ocimum basilicum L.) on mice. Subjects and methods: The experiments were conducted according to heat stimulation (hot plate) and needle slide methods. In each experiment, mice were divided into 4 groups of 10 each, in which the negative control group was given distilled water, the positive one took the control drug, and the others were treated with basil extracts at the doses of 2.4 and 7.2 g/kg/day for 7 consecutive days. Mice in the control groups were drunk codeine phosphate 20 mg/kg or aspirin at a dose of 150 mg/kg depending on being in the hot plate or the needle pricking methods, respectively. The research indicators including response time to heat, pain force and pain response time of an individual mouse before and after drug administration were recorded. This study was conducted between October and November 2021 at Hanoi Medical University, Vietnam. Results: At oral doses of 2.4 and 7.2 g/kg/day x 7 days, basil extract showed better central analgesic effects in the treated groups than that in the control group (p &lt; 0.001), but these pain relief levels were lower than that of codeine phosphate at a dose of 20 mg/kg/day (p &lt; 0.001). In addition, basil extract had better effects on peripheral analgesia in the treated group than that in the control group (p &lt; 0.05 and p &lt; 0.01) and these effects were equivalent to those of aspirin at a dose of 150 mg/kg/day. Conclusions: The aqueous extract of basil has both central and peripheral analgesic effects in white mice at the dose regimens of 2.4 and 7.2 g/kg/day×7 consecutive days.

In five wastewater treatment plants in Xinjiang, China: Removal processes for illicit drugs, their occurrence in receiving river waters, and ecological risk assessment

Residues of illicit drugs are frequently detected in wastewater, but data on their removal efficiency by wastewater treatment plants (WWTPs) and the ecological risks to the aquatic environment are lacking in this study. The research evaluates the residues, mass load, drug removal efficiency, and risk assessment of illicit drugs in WWTPs and aquatic environments (lakes) in Xinjiang, China. Initially, the concentration (incidence) and mass load of 10 selected illicit drugs were analyzed through wastewater analysis. The detected substances included methamphetamine (METH), morphine (MOR), 3,4-methylenedioxy methamphetamine (MDMA), methadone (MTD), cocaine (COC), benzoylecgonine (BE), ketamine (KET), and codeine (COD), with concentrations ranging from 0.11 ± 0.01 ng/L (methadone) to 48.26 ± 25.05 ng/L (morphine). Notably, morphine (59.74 ± 5.82 g/day) and methamphetamine (41.81 ± 4.91 g/day) contributed significantly to the WWTPs. Next, the drug removal efficiency by different sewage treatment processes was ranked as follows: Anaerobic-Oxic (A/O) combined Membrane Bio-Reactor (MBR) treatment process > Oxidation ditch treatment process > Anaerobic-Anoxic-Oxic (A2/O) treatment process > Anaerobic-Anoxic-Oxic combined Membrane Bio-Reactor treatment process. Finally, the research reviewed the concentration and toxicity assessments of these substances in the aquatic environment (lakes). The results indicated that Lake1 presented a medium risk level concerning the impact of illicit drugs on the aquatic environment, whereas the other lakes exhibited a low risk level. As a result, it is recommended to conduct long-term monitoring and source analysis of illicit drugs, specifically in Lake1, for further investigation. In conclusion, to enhance the understanding of the effects of illicit drugs on the environment, future research should expand the list of target analytes.

Fabrication of molecularly imprinted electrochemical sensors for sensitive codeine detection

Codeine (COD) is a natural opiate alkaloid obtained from hashish or prepared by methylation from morphine, widely used as an analgesic, antitussive, and antidiarrheal drug. A sensitive and selective electrochemical sensor based on molecular imprinting polymer (MIP) was developed to detect COD in tablet form and biological fluid samples. The polymeric thin film on the glassy carbon electrode (GCE) surface was formed using template molecule COD, a functional monomer based on amino acid N-methacryloyl-L-tryptophan (MA-Trp), basic monomer 2-hydroxyethyl methacrylate (HEMA), cross-linker ethylene glycol dimethacrylate (EGDMA), and the pore-making sacrificial material zinc oxide (ZnO). The developed MIP-based electrochemical sensor (MA-Trp@MIP/GCE) was characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) methods. The electrochemical properties of the sensor were examined using differential pulse voltammetry (DPV). Under optimum experimental conditions, the dynamic linear range of the developed sensor was calculated as 0.1–1.0 pM and the detection limit of 0.0150 pM. The current electrochemical sensor technique also demonstrated outstanding recovery in human urine, synthetic serum samples, and tablet form, with relatively high recoveries of 98.5%, 101.4%, and 101.5%, respectively. Moreover, the MA-Trp@MIP/GCE sensor exhibited good reproducibility, repeatability, stability, and fast response time for the electrochemical analysis of COD. The presented sensor successfully determined COD in tablet and biological fluid samples.

SOLUBILITY AND THERMODYNAMIC PROPERTIES OF CODEINE PHOSPHATE IN THE MIXTURES OF POLYETH- YLENE GLYCOL 400 AND ETHANOL AT DIFFERENT TEM- PERATURES

In the present work, the solubility values of codeine phosphate in the binary mixtures of polyeth- ylene glycol 400 and ethanol are determined via a shake-flask method followed by spectrophotometry in the temperature range of 293.2–313.2 K. The attained solubility values of codeine phosphate are correlated with some linear and non-linear co-solvency models. Additionally, the density of saturated mixtures is also presented by the Jouyban-Acree model at various temperatures. The accuracy of each used model is validated by the mean relative deviations (MRD %) of the back-calculated solubility and density data. The apparent thermodynamic properties of codeine phosphate dissolution are also calcu- lated using the van't Hoff and Gibbs equations.

Simultaneous determination of paracetamol and codeine phosphate in pharmaceuticals using molecular absorption spectroscopy and classical least squares method

In this article, a combined method of molecular absorption spectroscopy and classical least squares is used to simultaneously determine paracetamol (PAR) and codeine phosphate (COP) in pharmaceutical samples without the need for prior separation or extraction steps. The absorption spectra of standard solutions and samples were measured in the wavelength range of 210 to 290 nm with a step size of 0.5 nm. The concentrations of PAR and COP in the sample solutions were calculated using a self-made program written in Microsoft Excel 2016 and Visual Basic for Applications (VBA). The reliability of the method was verified through the accuracy and reproducibility of the measurements when analyzing PAR and COP in Effer-Paralmax® Codeine tablets, and comparing the average values of their concentrations in the samples with the standard HPLC method.

Efficacy of compound pholcodine syrup and compound codeine phosphate oral solution on lung cancer-related cough

Objective: To assess the clinical efficacy of compound pholcodine syrup and compound codeine phosphate oral solution on lung cancer-related cough. Methods: A total of 60 patients diagnosed with middle-advanced stage lung cancer and had lung cancer-related cough in the Department of Geriatric Oncology of Chongqing University Cancer Hospital from January to May 2022 were prospectively enrolled. According to the random number table method, the patients were divided into two groups: observation group and control group. The observation group [n=30, with 21 males and 9 females, and aged (62.3±10.4) years] received compound pholcodine syrup treatment, while the control group [n=30, with 21 males and 9 females, and aged (62.0±8.1) years] received compound codeine phosphate oral solution treatment. The dosage of the two drugs was 15 ml each time, 3 times a day, and the treatment course was 5 days. The antitussive effectiveness, cough severity and quality of life (Leicester Cough Questionnaire in Mandarin-Chinese scale) were observed and compared between the two groups 3 days and 5 days after the treatment. Results: All 60 patients completed the study. Both regimens were effective in controlling lung cancer-related cough. After 3 days treatment, the antitussive effective rate of the observation group and the control group was 83.3% (25/30) and 73.3% (22/30), respectively, with no statistically significant difference (P=0.347). Likewise, after 5 days treatment, the antitussive effective rate of observation group and control group was 90.0% (27/30) and 86.6% (26/30), respectively, with no statistically significant difference (P=0.687). There was no statistically significant difference in the cough severity between observation group [moderate and severe cough: 56.7% (17/30)] and control group [moderate and severe cough: 67.7% (20/30)] (P=0.414). After 3 days treatment, cough symptoms were relieved in both groups. Patients with mild cough accounted for 73.3% (22/30) in the observation group and 56.7% (17/30) in the control group, and the difference was not statistically significant (P=0.331). Moreover, after 5 days treatment, there was also no significant difference in mild cough between observation group [86.7% (26/30)] and control group [66.7% (20/30)] (P=0.067). Meanwhile, there were no significant differences in the physiological score, psychological score, social score and total score of the Leicester Cough Questionnaire in Mandarin-Chinese scale before the treatment, after 3 days and 5 days treatment between the two groups (all P>0.05). The incidence of both xerostomia and constipation in the observation group was 0, which was lower than those of the control group [20.0% (6/30) and 20.0% (6/30)] (both P<0.05). Conclusions: Both compound pholcodine syrup and compound codeine phosphate oral solution are effective in treating lung cancer-related cough with similar antitussive effectiveness. Compound pholcodine syrup has a lower incidence of xerostomia and constipation than control group, with a better safety profile.

Accumulation and risk prioritization of psychoactive substances in the critically endangered Yangtze finless porpoise.

Psychoactive substances have been identified as a kind of emerging contaminants in aquatic environment and pose potential adverse effects on aquatic animals. Yangtze finless porpoise, a critically endangered species in China, is also facing the threat of psychoactive substances. In this study, the accumulation characteristics and risk prioritization of psychoactive substances were investigated in Yangtze finless porpoise collected from Poyang Lake (PYL) and Tian-E-Zhou Oxbow (TZO) in Yangtze River basin. The levels of psychoactive substances were detected in the range of below method detection limits (MDLs) to 98.4ng/mL in the serum of Yangtze finless porpoise. Codeine (COD) and methamphetamine were identified as the major substances due to the highest residual levels with a median concentration of 0.72ng/mL and 0.33ng/mL, respectively. The total concentrations of psychoactive substances in the porpoise collected from TZO was significantly higher than those from PYL. Risk analysis based on effect ratio derived from the ratio of steady-state psychoactive substance serum concentration in the porpoise and human therapeutic plasma concentration revealed that COD was the substance with the highest risk among the psychoactive substances detected, followed by lysergic acid diethylamide (LSD), morphine, alprazolam (ALPZ) and lormetazepam. Location-specific risk prioritization of psychoactive substances found that the top 3 substances are LSD, lorazepam (LORZ) and ALPZ in PYL, and COD, LSD and LORZ in TZO. The results disclose the accumulation of psychoactive substances in Yangtze finless porpoise and suggest that the potential adverse effects should be concerned.

Evaluation of the safety and efficacy of codeine phosphate and chlorpheniramine maleate in a fixed dose composition for the management of dry cough in adults: an open label phase IV clinical trial

Background: Dry cough is one of the most common symptoms for which patients seek medical attention. It not only causes discomfort in patients, but also hampers their daily work and routine. Since there is no specific underlying cause for dry cough, a definitive treatment is still not available. Several cough suppressants have been used for the treatment of dry cough including codeine which reduces discomfort. However, some reports suggest that use of codeine at high doses leads to sedation and drowsiness. To evaluate the safety and efficacy of codeine, a clinical trial for fixed dose composition of codeine phosphate and chlorpheniramine maleate was conducted.Methods: The trial was conducted on 219 adults with prior symptoms of dry cough. Safety was evaluated on the basis of the change in patient’s vital parameters, any adverse event or severe adverse event that occurred during the course of study. Efficacy was assessed on the basis of cough severity scores, number of night awakenings due to cough, and overall decline in cough.Results: According to the investigator's evaluation the product was safe to use as no significant changes in the patient’s vital parameters were observed during the course of study. Also, no severe adverse events were reported. Administration of the investigation product significantly decreased cough severity and frequency at the 7th day of the study.Conclusions: This study suggests, FDC of codeine phosphate 10 mg and chlorpheniramine maleate 4 mg per 5 ml oral syrup is safe and efficacious for the treatment of dry cough.

What are dietitians prescribing? An evaluation of the prescribing practice of a nutrition support dietitian

Background In 2016, registered dietitians in the UK were granted supplementary prescribing rights. There is currently little published data on the prescribing practices of dietitians. Aim The prescribing practice of a nutrition support dietitian specialising in intestinal rehabilitation was evaluated. Methods Over a six-month period, the dietitian collected data on her prescribing practice using the hospital proforma and then transferred the information to Excel. Findings Over a 6 month period, the dietitian prescribed for 24 patients. The most common prescriptions included parenteral nutrition, intravenous fluids and electrolytes, oral rehydration solutions and micronutrients. Medications deprescribed included codeine phosphate, loperamide, lansoprazole, forceval and folic acid. Conclusion The evaluation demonstrated that a nutrition support dietitian was able to prescribe a range of different medications related to the nutritional management of patients with intestinal failure. Further work is required to assess patient satisfaction, economic impact and attitude of other healthcare professionals.

Simultaneous determination of some opioid drugs using Cu-hemin MOF@MWCNTs as an electrochemical sensor

Due to its toxicological and pharmacological activity, the misuse and overuse of morphine (MO), codeine (CO), and heroine have attracted attention in the medical and forensic toxicology fields. This study proposed a new electrochemical sensor with an acceptable detection limit, linear range, and selectivity for simultaneous determination of MO and CO. This sensor is based on Cu-Hemin metal-organic framework (CHM) and multiwall carbon nanotubes (MWCNTs). First, a facile chemical method was chosen to synthesize CHM and then composite it with MWCNTs. Afterward, the structure of CHM@MWCNTs was verified by XRD, FT-IR, Raman spectroscopy, UV–vis, ICP-OES, FE-SEM, EDX, and elemental mapping. In the next step, under optimal conditions, this electrochemical sensor can sensitive simultaneous determination of MO and CO, showing a dynamic concentration range from 0.09 to 30 μM for both species and a low detection limit of 9.2 nM and 11.2 nM for MO and CO, respectively. Moreover, the applicability in real samples was confirmed by the simultaneous determination of MO and CO in human urine and MO injection. This work reveals a trustable sensor based on MOF and MWCNTs to simultaneously determine opioid drugs in clinical application.

A novel self-aggregated gold nanoparticles based on sensitive immunochromatographic assays for highly detection of opium poppy in herbal teas

Opium poppy abused in food has aroused public concerns due to its serious side effects. Effective monitoring is essential to fight the abuse crisis. Herein, we synthesized an easily prepared, affordable, accessible highly aggregated gold nanoparticles (AGNPs) performing in lateral flow immunoassay (LFIA) for detection opium poppy in herbal teas. Simultaneously, a LFIA based ontime-resolved fluorescent microspheres (TRFMs) was developed as contrastive method. In this study, morphine (MOR), codeine (COD) and thebaine (THE) were as the specific recognition markers of opium poppy. Results demonstrated the quantitative limits of detection were 0.0049/0.0053/0.084, 0.034/0.037/0.37 ng mL−1 for AGNPs/TRFMs-LFIA, respectively. The recoveries were 95%-107.5%/91%-106.7% with coefficient of variation was 1.6%-6.6%/1.8%-7.2%, indicating excellent accuracy and precision. Parallel experiments among AGNPs/TRFMs-LFIA and LC-MS/MS analysis showed good correlation. Overall, AGNPs-LFIA executed quantitative analysis within 15 min on the basis of simple treatment while providing a rapid and sensitive analysis strategy for illegal drugs abused.

Investigation of pharmaceutical compounds (Metronidazole, Rosuvastatin and Codeine phosphate) removal by Synechocystis sp. PCC6803 microalga

The uncontrolled entry of pharmaceutical compounds (PCs) into water sources causes irreversible damages to microorganisms. This study aimed to evaluate the capability of Synechocystis sp. PCC6803 microalga to remove three PCs, namely Metronidazole in 1, 3, and 5 mg/L, Rosuvastatin in 200, 400, and 600 mg/L, and Codeine phosphate in 50, 150, and 250 mg/L. These PCs have not been effectively removed by chemical and physical wastewater treatment methods. Adding Metronidazole to the culture medium resulted in a 70% reduction in biomass production; while the amount of protein produced at the concentration of 5 mg/L increased about 3 times compared to the control culture. The culture medium containing 600 mg/L Rosuvastatin increased the total lipid production by more than 50%. The biomass and protein produced in culture medium containing Codeine phosphate were not significantly different compared with the control. Moreover, the drugs removal efficiency of Synechocystis was 80% for Metronidazole and almost 100% for Rosuvastatin and Codeine Phosphate. Metronidazole, which is a lipophilic drug, bonds to the cell surface of microalgae through the formation of chemical bonds between its aromatic rings and functional groups on the surface of extracellular substrates. However, Rosuvastatin and Codeine phosphate which are hydrophilic drugs can enter the cells, where they are degraded by intra-cellular enzymatic mechanism; thus, they were removed by cell biodegradation mechanism in cells. The findings of this study can be potentially used in e.g., hospital wastewater treatment sustainably and economically using microalgae in the future.

Analgesia and Side Effects of Codeine Phosphate Associated with Paracetamol Versus Oxycodone After the Extraction of Mandibular Third Molars: A Randomized Double-Blind Clinical Trial Using the Split-Mouth Model.

To assess the analgesia and side effects of 10mg oxycodone as compared to 30mg of codeine phosphate associated with 500mg of paracetamol after bilateral lower third molar extraction. This is a prospective, randomized, double-blind study applied to a sample of 16 patients. They were evaluated for seven days postoperatively, and the mean score of the visual analogue scale (VAS) of pain between test and control medications was assessed by the Wilcoxon distribution. The side effects of these medications were assessed by the Q Cochran test. A p value of < .05 was considered statistically significant. The mean score of the VAS of pain was higher in the oxycodone side, where few patients reported the use of rescue analgesic. There was no report of rescue medication in codeine phosphate associated with paracetamol side. The most common side effects reported in both groups, predominantly in patients using the oxycodone, were drowsiness, dizziness, and headache. The use of codeine phosphate associated with paracetamol after the extraction of impacted mandibular third molars is a better choice than oxycodone for controlling postoperative pain. RBR-8ntwmyq 07/07/2021.

Antitussive effect of granule formulation on SO gas-induced cough in experimental animals

All over world cough is a common symptom in respiratory disease. When cough becomes severe, opioids act as a potent drug, but they have various side effects like sedation, constipation, etc. Therefore, there is a need to have an effective antitussive formulation, which doesn’t have respiratory depressant activity. The present study was carried out to evaluate the antitussive activity of granules containing extract using a cough model induced by Sulphur dioxide gas in experimental mice. The antitussive effect of granule formulation on SO gas induced cough in experimental animals, which compared to standard codeine sulphate and the result was determined by statistical analysis. The antitussive activity of the granules tested in control, standard and test animal group respectively, it was compared to standard codeine sulphate (10, 15, 20 mg/kg body weight). Codeine sulphate as a standard drug for suppression of cough, act as potent antitussive agent, which produced 25.29%, 33.33%, 47.13% inhibition in cough at a dose of 10mg/kg, 15mg/kg and 20mg/kg respectively, whereas, codeine sulphate (20mg/kg) showed a maximum inhibition of 47.13% (p&amp;#60;0.01) after 60 min. of experiment. The test group of mice was showed 41.17%, inhibition, in cough on treatment with granules after 60 min. of an experiment. This is very significant or nearly equal to a maximum dose of codeine sulphate (20mg/kg). Statistical analysis shows very significant antitussive effects of granules at the level of p&amp;#60;0.01 in inhibiting the cough reflex at 200 mg/kg body wt. in comparison to the control group.

Synthesis of a novel polydopamine and C18 dual-functionalized magnetic core-shell mesoporous nanocomposite for enrichment and analysis of widely abused illegal drugs in urine samples on site and in the laboratory

In this study, a novel polydopamine and C18 dual-functionalized magnetic core-shell mesoporous silica (Fe3O4@nSiO2@mSiO2@PDA-C18) nanocomposite was designed and synthesized, which was employed as an adsorbent to extract illegal drugs from urine samples by magnetic solid-phase extraction (MSPE) procedures. The as-prepared nanocomposite was fully characterized and combined with ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to monitor 12 trace illegal drugs and metabolites, including 6-monoacetylmorphine (6-MAM), morphine (MOR), codeine (COD), amphetamine (AMP), methamphetamine (MAMP), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), ketamine (KET), norketamine (NK), cocaine (COC), benzoylecgonine (BZE) and methcathinone (MC). Optimal MSPE procedures were achieved by fully investigating parameters of activation, adsorption, washing and desorption steps. The MSPE-UHPLC-MS/MS method offered high sensitivity with limit of detection (LOD) range of 0.005–0.05 ng mL-1 and good linearity with the concentration of 0.01–1000 ng mL-1. Also, the intra- and inter-day recovery respectively ranged in 90.2–105.0% and 89.8–107.4%, and the intra- and inter-day precision was in the range of 0.5–14.0% and 1.2–10.0%, respectively. By application to real urine samples, the proposed method could not only be equally sensitive for quantifying 12 illegal drugs in urine but also significantly reduce the pretreatment time when comparing with methods based on solid-phase extraction. Furthermore, the designed dual-functionalized adsorbents could also be applied for on-site determination of MAMP in urine coupled with urine test kit, and the detection threshold of MAMP urine test kit remarkably reduced from 1000 ng mL-1 to 50 ng mL-1. Therefore, the present method was a convenient, economic and sensitive approach for determining illegal drugs in urine samples both on site and in the laboratory.

Stability of Cocaine, Opiates, and Metabolites in Dried Saliva Spots.

Drug abuse still represents a global problem, and it is associated with an increased risk of diseases, injuries, and deaths. Cocaine (COC) and opiates are the most abused drugs and account for a significant number of fatalities. Therefore, it is important to develop methods capable of effectively identifying and quantifying these substances. The present study aims to evaluate the long-term stability of COC, ecgonine methylester (EME), benzoylecgonine (BEG), cocaethylene (COET), norcocaine (NCOC), morphine (MOR), codeine (COD) and 6-monoacetylmorphine (6-MAM) in oral fluid samples. The analytes of interest were isolated from the matrix (50 µL) using the dried saliva spots (DSS) sampling approach and were subsequently analyzed by gas chromatography coupled with tandem mass spectrometry (GC–MS/MS). The parameters that could influence the stability of the target compounds were studied, and these were storage temperature, light, use of preservatives (and respective concentrations), and time. The effects of each parameter were evaluated using the design of experiments (DOE) approach. The stability of the target analytes was improved when the DSS were stored at room temperature, in the presence of light and using 1% sodium fluoride. The best conditions were then adopted for the DSS storage and long-term stability was assessed. COD was only stable for 1 day, EME was stable for 3 days, COC, COET, NCOC and 6-MAM were stable for 7 days, MOR for 14 days and BEG remained stable throughout the study (136 days). This is the first study that evaluates the stability of these compounds in oral fluid samples after application in DSS cards, and optimizes the conditions in order to improve their stability.

Synthesis and Introducing Au-Cu Alloy Nanoparticles/Porous Silicon as a Novel Modifier of Screen Printed Carbon Electrode in Simultaneous Electrocatalytic Detection of Codeine and Acetaminophen

In the present study, a bimetallic nanostructure of gold-copper (Au-CuNPs) was decorated on the surface of porous silicon (PSi) using an easy galvanic replacement reaction between metal ions and PSi in the presence of 0.1 M hydrofluoric acid solution. The morphology and structures of the Au-CuNPs@PSi nanocomposite were characterized using X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscopy (FE-SEM), fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) energy-dispersive X-ray spectroscopy (EDX) and cyclic voltammetry (CV) techniques. Then, prepared nanocomposite was used as a modifier in screen-printed carbon electrode (SPCE) for the highly sensitive simultaneous determination of codeine (COD) and acetaminophen (ACE). The combination of PSi and metals nanoparticles provide a porous and high surface area with excellent electrical conductivity which leads to reduce the peak potentials and enhance the oxidation peak currents of COD and ACE at the surface of the Au-CuNPs@PSi/SPCE nanosensor. The dynamic linear ranges were obtained from 0.06 to 0.6 μM for both COD and ACE and the detection limits (3.0 S/N) estimated 0.35 μM for COD and 0.30 μM for ACE, respectively. Moreover, recovery tests were carried out in real samples such as urine, human blood plasma, and tablets.