An assessment of qualitative and quantitative cannabinoids analysis in selected commercially available cannabis oils in Argentina.

In recent years, the therapeutic use of cannabis products, especially cannabis oils, has increased significantly, due to the pharmacological potential of their cannabinoids, for the treatment of conditions, such as pain management, cancer, and epilepsy. In Argentina, patients with medical prescriptions can access to cannabis oil, through self-cultivation, a third-person (grower or importer), or a civil organization authorized for that purpose. However, these products remain largely unregulated in Argentina, and information available regarding labeling accuracy, especially cannabidiol (CBD)/ Δ9-tetrahydrocannabinol (Δ9-THC) concentrations are inconsistent or nonexistent, nor long-term product stability, and lot to lot variability. Understanding these properties is fundamental if these products are to be used in patients with a determinate pathology. Therefore, we analyzed commercially available cannabis oils (n: 500) in Argentina for qualitative and quantitative cannabinoids content. In order to provide a detailed overview of their cannabinoids profiles, and determine Δ9-THC, CBD, and cannabinol (CBN) concentrations, samples were diluted and analyzed by gas chromatography- mass spectrometry (GC/MS). Most of the samples tested positive for cannabinoids (n: 469) with Δ9-THC and CBD as the predominant cannabinoids. Among products tested, only 29.8% (n: 149) gave specific CBD label claims, and testing indicated a CBD tested positive of 70.5% (n: 105). For products (n: 17) with a THC-free label claim, testing indicated 76.5% (n: 13) of Δ9-THC positive, and cannabinoids were not detected in four products. Δ9-THC concentrations ranged from 0.1 to 143.0 mg/mL, CBD concentrations from 0.1 to 125.3 mg/mL, and CBN concentrations from 0.04 to 60.10 mg/mL; CBN/ Δ9-THC ratios ranged from 0.0012 to 2.31, and CBD/ Δ9-THC ratios from 0.0008 to 178.87. Furthermore, the (Δ9-THC + CBN)/CBD ratio of most samples was greater than one. In summary, our results indicate that cannabis oil products show wide variability in cannabinoids content, purity, and labeling.

Optimization and validation of simultaneous analyses of ecgonine, cocaine, and seven metabolites in human urine by gas chromatography-mass spectrometry using a one-step solid-phase extraction.

The presence of ecgonine in urine has been proposed as an appropriate marker of cocaine use. Only a few methods have been published for their determination along with cocaine and the rest of its metabolites. Due to their high polarity and consequent solubility in water, these have low recoveries, which is why it is necessary to increase the sensitivity, by the formation of hydrochloric salts or multiderivatization of the analytes or by performing two solid-phase extractions (SPEs), considerably increasing the time and cost of the analysis. This work describes a fast and fully validated procedure for the simultaneous detection and quantification of ecgonine, ecgonine-methyl-ester, benzoylecgonine, nor-benzoylecgonine, m-hydroxybenzoylecgonine, cocaethylene, cocaine, norcocaine, and norcocaethylene in human urine (500 µL) using one SPE and simple derivatization. Separation and quantification were achieved by gas chromatography-electron ionization-mass spectrometry (GC-EI-MS) in selected-ion monitoring mode. Quantification was performed by the addition of deuterated analogs as internal standards. Calibration curves were linear in the adopted ranges, with determination coefficients higher than 0.99. The lower limits of quantification ranged from 2.5 to 10 ng/mL. The intra- and inter-day precision, calculated in terms of relative standard deviation, were 1.2%-14.9% and 1.8%-17.9%, respectively. The accuracy, in terms of relative error, was within a ± 16.4% interval. Extraction efficiency ranged from 84% to 103%. Compared with existing methods, the procedure described herein is fast, since only one SPE is required, and cost-effective. In addition, this method provides a high recovery for ecgonine, resulting in a better alternative to the previously published methods.

Dextrophropoxyphene effects on QTc-interval prolongation: Frequency and characteristics in relation to plasma levels.

OBJECTIVE: To evaluate frequency and risk factors for dextropropoxypheneinduced QT-interval prolongation in the clinical setting. DESIGN: Prospective, noninterventional, observational, longitudinal cohort approach. Electrocardiograms were blindly evaluated by independent professionals. SETTING: General ward of a public hospital of metropolitan Buenos Aires. PATIENTS, PARTICIPANTS: Ninety-two patients with indication of receiving dextropropoxyphene for analgesic purposes were included consecutively. All patients finished the study. INTERVENTIONS: All patients were monitored with electrocardiographic controls (previous to drug administration and during steady state) to diagnose and quantify changes in the duration of the QTc interval. MAIN OUTCOME MEASURE: Frequency of drug-induced QTc interval prolongation, QTc interval correlation with plasma drug, and metabolite levels. RESULTS: Ninety-two patients were studied (50 percent males). All patients received a (mean ± SD [range]) dextropropoxyphene dose of 125 ± 25[100-150] mg/d. Dextropropoxyphene and norpropoxyphene concentrations were 112 ± 38[45-199] and 65 ± 33[13-129] ng/mL, respectively. The intra-treatment QTc interval was >450 ms in only one patient (only with the Hodge correction). There were no cases of QTc > 500 ms, and there were no significant differences in the results considering different correction formulas (Bazzet, Fridericia, Framingham, Hodges). Dextropropoxyphene concentrations correlated with QTc (R > 0.45) interval and ΔQTc (R 0.52-0.87), whereas norpropoxyphene correlation was even greater for QTc (R > 0.40-0.64) and ΔQTc (R > 0.47-0.92). Depending on the QTc correction formula, eight patients presented ΔQTc > 30 ms and one patient with ΔQTc > 60 ms. No patient presented arrhythmia during the study. CONCLUSIONS: The authors did not observe a relationship between dextropropoxyphene and QTc interval prolongation at the therapeutic doses used in Argentina.

Simultaneous quantitation of meperidine, normeperidine, tramadol, propoxyphene and norpropoxyphene in human plasma using solid-phase extraction and gas chromatography/mass spectrometry: Method validation and application to cardiovascular safety of therapeutic doses.

RATIONALE: Several opioid analgesics have been related to the prolongation of cardiac repolarization, a condition which can be fatal. In order to establish a correct estimation of the risk/benefit balance of therapeutic doses of meperidine, normeperidine, tramadol, propoxyphene and norpropoxyphene, it was necessary to develop an analytical method to determinate plasma concentrations of these opioids. METHODS: Here we describe a method which incorporates strong alkaline treatment to obtain norpropoxyphene amide followed by a one-elution step solid-phase extraction, and without further derivatization. Separation and quantification were achieved by gas chromatography/electron ionization mass spectrometry (GC/EI-MS) in selected-ion monitoring mode. Quantification was performed with 500 µL of plasma by the addition of deuterated analogues as internal standards. RESULTS: The proposed method has been validated in the linearity range of 25-1000 ng/mL for all the analytes, with correlation coefficients higher than 0.990. The lower limit of quantification was 25 ng/mL. The intra- and inter-day precision, calculated in terms of relative standard deviation, were 2.0-12.0% and 6.0-15.0%, respectively. The accuracy, in terms of relative error, was within a ± 10% interval. The absolute recovery and extraction efficiency ranged from 81.0 to 111.0% and 81.0 to 105.0%, respectively. CONCLUSIONS: A GC/MS method for the rapid and simultaneous determination of meperidine, normeperidine, tramadol, propoxyphene and norpropoxyphene in human plasma was developed, optimized and validated. This procedure was shown to be sensitive and specific using small specimen amounts, suitable for application in routine analysis for forensic purposes and therapeutic monitoring. To our knowledge, this is the first full validation of the simultaneous determination of these opioids and their metabolites in plasma samples.

Meperidine-induced QTc-interval prolongation: prevalence, risk factors, and correlation to plasma drug and metabolite concentrations
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A prolongation of the QTc-interval has been described for several opioids, including pethidine (meperidine). OBJECTIVE: To evaluate in the clinical setting the frequency and risk factors associated with the QT-interval prolongation induced by meperidine. RESEARCH DESIGN AND METHODS: We recruited patients requiring meperidine administration and recorded their medical history and comorbidities predisposing to QT-interval prolongation. Ionograms and electrocardiograms (ECGs) were performed at baseline and during treatment; QT was corrected using the Bazzet, Fridericia, Framinghan, and Hogdes formulas. We measured meperidine and normeperidine by gas chromatography. Values are expressed as mean ± SD (range). RESULTS: 58 patients were studied (43.1% males). All patients received meperidine at a dose of 304 ± 133 (120 - 480) mg/day. Meperidine and normeperidine concentrations were 369 ± 60 (265 - 519) and 49 ± 17 (15 - 78) ng/mL, respectively. Intratreatment control found QTcB 370 ± 30 (305 - 433), QTcFri 353 ± 35 (281 - 429), QTcFra 360 ± 30 (299 - 429), QTcH 359 ± 27 (304 - 427), ΔQTcB +9 ± 42 (-90 to +136), ΔQTcFri +4 ± 45 (-86 to +137), ΔQTcFra +5 ± 40 (-77 to +129), and ΔQTcH +7 ± 40 (-76 to +129) ms. Meperidine concentration correlated with QTc-interval (R > 0.36) and ΔQTc (R > 0.69) but the correlation was even better for normeperidine concentration, QTc (R > 0.52) and ΔQTc (R > 0.81). Depending on the QTc correction formula used, 13 - 15 patients (22.41 - 25.86%) presented ΔQTc values > 30 ms, and 7 - 8 patients (12.07- 13.79%) showed ΔQTc values > 60 ms. Renal failure was associated with risk for ΔQTc > 30 ms of 3.74 (IC95% 1.73 - 8.10) and for ΔQTc > 60 ms of 4.27 (IC 95% 1.26 - 14.48). No patient developed arrhythmias during the study. CONCLUSIONS: Meperidine treatment causes ECG changes (QTc-interval prolongation) in high correlation with normeperidine plasma concentration. Renal failure increases the risk.
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Perfil de consumo de cocaína, cannabis y opiáceos en el laboratorio toxicológico CENATOXA / Profile of consumption of cocaine, cannabis and opiates in the toxicology laboratory CENATOXA

Con el propósito de conocer, en la población que concurre al laboratorio del CENATOXA, qué droga de abuso se consume más, cuál es la modalidad de consumo y el perfil de la consulta, se realizó un estudio retrospectivo de 2.635 casos a los que durante el período 1995-2006 se les solicitó investigación en orina de cannabis, cocaína y opiáceos. Los análisis se realizaron utilizando pruebas inmunológicas, cromatografía en capa delgada normalizada y cromatografía gaseosa-espectrometría de masas. El 20% de las muestras (n=529) resultaron positivas, correspondiendo el 50,66% a cannabis, el 37,43% a cocaína, el 2,08% a opiáceos y el 9,83% a la combinación cannabis-cocaína. Los varones constituyeron el 62% de los casos positivos. El mayor consumo de cannabis se observó entre los 11 y 30 años, el de cocaína entre los 21 y 40 años y la combinación de ambas drogas entre los 11 y 30 años. Los motivos de la solicitud de análisis correspondieron mayoritariamente y en proporciones similares al control de la adicción (31,1%) y a la sospecha de consumo (29,67%). El cannabis fue la droga ilegal más usada, predominó el monoconsumo, los principales usuarios fueron varones y los más comprometidos fueron los menores de 30 años.

A study was conducted in order to know what drugs of abuse are most commonly consumed by the population that comes to CENATOXA, as well as which the consumption patterns and consultation profiles are. A retrospective study was conducted in 2,635 cases for which, during 1995 to 2006, a toxicologycal urine analysis of cocaine, cannabis and opiates was requested. The analytical methodologies applied were immunoassay tests, standardized thin layer chromatography and gas chromatography-mass spectrometry. In the studied sample (n=529), 20% were positive: 50.66% was due to cannabis, 37.43% to cocaine, 2.08% to opiates and 9.83% to combination of cannabis-cocaine. Sixty-two per cent of positive cases were male subjects, and the highest consumption of cannabis was seen in the 11 to 30 year-old age group; that of cocaine was seen in the 21 to 40 year-old age group and the combination of cannabis-cocaine in the 11 to 30 year-old group. In assessing the reason for test request a similar predominance of addiction control (31.1%) and drug abuse suspicion (29.67%) was found. Cannabis is the drug of abuse most commonly consumed; mono consumption is usual in this population and drug consumption is higher in males and people under 30 years old.