The impact of initiation: Early onset marijuana smokers demonstrate altered Stroop performance and brain activation.

Marijuana (MJ) use is on the rise, particularly among teens and emerging adults. This poses serious public health concern, given the potential deleterious effects of MJ on the developing brain. We examined 50 chronic MJ smokers divided into early onset (regular MJ use prior to age 16; n=24) and late onset (age 16 or later; n=26), and 34 healthy control participants (HCs). All completed a modified Stroop Color Word Test during fMRI. Results demonstrated that MJ smokers exhibited significantly poorer performance on the Interference subtest of the Stroop, as well as altered patterns of activation in the cingulate cortex relative to HCs. Further, early onset MJ smokers exhibited significantly poorer performance relative to both HCs and late onset smokers. Additionally, earlier age of MJ onset as well as increased frequency and magnitude (grams/week) of MJ use were predictive of poorer Stroop performance. fMRI results revealed that while late onset smokers demonstrated a more similar pattern of activation to the control group, a different pattern was evident in the early onset group. These findings underscore the importance of assessing age of onset and patterns of MJ use and support the need for widespread education and intervention efforts among youth.

Determination of Gentian Violet in human urine and poultry feed by high performance liquid chromatography with electrochemical detection using a carbon fibre microelectrode flow cell.

A sensitive and relatively selective high performance liquid chromatographic method for the determination of Gentian Violet (GV) in human urine and chicken feed is described. The method is based on solid-phase extraction, with subsequent reversed-phase chromatographic separation on a cyano column and amperometric detection using a carbon fibre microelectrode flow cell operated at + 1.3 V. The peak currents were directly proportional to GV concentration over the concentration range 1-30 ppb (for urine samples analysis) and 1-20 ppm for poultry feed analysis. Using this method, the minimum detectable concentration was estimated to be 0.5 ppb. The method was applied successfully to the determination of GV in human urine and in chicken feed, and it was concluded that the method could be applied to the quantitative analysis of GV in the presence of its major metabolite, leuco GV. In the proposed procedure, the occurrence of matrix effects during urine analysis was significant. The electrochemical pretreatment regime described in this paper was used to overcome these effects. Recovery studies were performed on both the human urine and chicken feed samples. The recovery of GV ranged from 92 to 96% in both matrices, with a relative standard deviation of less than 5.5%.

Simultaneous determination of levodopa, carbidopa and their metabolites in human plasma and urine samples using LC-EC.

In this study levodopa (L-DOPA), carbidopa (C-DOPA) and their metabolites were resolved from other endogenous components present in human plasma and urine and determined quantitatively. The developed technique involved the use of a second pump, a switching valve, and a pre-column in the LC system in order to perform on-line sample clean-up and enrichment. This procedure is dependent on an effective removal of the many interfering matrix components that vitiate HPLC analysis. Several unknown endogenous electroactive compounds, present in plasma, were eliminated by the purification step, or suppressed by the pre-treatment or detection conditions. The analyses were separated on an Octyl-bonded reversed-phase column followed by amperometric detection using a carbon fibre microelectrode flow cell operated at +0.8 V versus silver/silver phosphate reference electrode. The cell was compatible with the mobile and the stationary phase used in the flow system without any complex surface reaction. The peak currents obtained for the different analytes were directly proportional to the analyse over the concentration range 0.02-4.0 microg ml(-1). Using this method, the minimum detectable concentration was estimated to be 5 and 8 ng ml(-1) for L-DOPA and C-DOPA, respectively. Recovery studies performed on human plasma samples ranged from 93.83 to 89.76%, with a relative standard deviation of < 6%. The intra- and inter-assay coefficients of variation were < 7%. The accuracy of the assay, which was defined as the percentage difference between the mean concentration found and the theoretical (true) concentration, was 12% or better. The electrochemical pre-treatment regime described in this work permitted a longer application of the same microelectrode. The method showed a good agreement with other available methods described in the introduction and offers the advantages of being simple, less time and labour consuming, does not require additional solvents for extraction, inexpensive and suitable for routine analysis and kinetic purposes.

A comparative bioavailability study of different aspirin formulations using on-line multidimensional chromatography.

A multi-dimensional column chromatographic method employing UV spectrometric detection was optimised and successfully used in a comparative bio-availability study of aspirin obtained from different commercially available oral dosage forms. Sample clean-up was achieved by on-line solid-phase extraction. In this study, the bioavailability of aspirin was compared in plain aspirin tablets, chewed tablets, effervescent tablets and Enteric-coated aspirin tablets. Blood samples were taken at frequent intervals after single dosing in ten healthy volunteers, the plasma samples were first treated with physostigmine sulphate to minimise enzymatic hydrolysis of aspirin to salicylate. The results showed the measured Tmax, Cmax, and AUC was significantly higher for soluble aspirin than for the other formulations and the t1/2 was shorter. This indicates the rapid absorption of aspirin from a soluble formulation compared with that from the other formulations. These differences suggest that the soluble formulation could be the aspirin of choice to treat patients suspected to be at high risk of myocardial infarction. The method performs, in a single step, an efficient extraction and clean-up of aspirin from human plasma. The calibration graph was linear over the calibration range 0.2-12 microg ml(-1) plasma with a limit of detection of 0.1 microg ml(-1). The intra- and inter-assay coefficients of variation were less than 6% and the recoveries ranged from 86 to 98%. The proposed method combines the advantages of being simple and selective in the presence of other potential interfering drugs and is suitable for routine analyses to obtain valuable information about the clinical effects of the drug and its use in prevention treatments of acute myocardial infarction. The whole procedure takes 7 min and is in agreement with other conventional methods.

Voltammetric study of salbutamol and application to its determination in a tablet dosage form and dissolution profiles for the dosage form.

The oxidative voltammetric behaviour of salbutamol at a glassy carbon electrode surface has been studied using cyclic voltammetry and differential pulse voltammetry. Oxidation of the drug was effected in a single irreversible, adsorption-controlled step in phosphate buffer. The process was found to be dependent on the ionic strength and the pH of the supporting electrolyte. The response was evaluated with respect to accumulation time, scan rate and other variables. Using differential pulse voltammetry following electrochemical pretreatment of the electrode surface, the drug yielded a well-defined voltammetric response in phosphate buffer, pH 5.0, at +0.75 V (vs SCE). This process could be used to determine salbutamol concentrations in the range 8 x 10(-7) M to 8 x 10(-5) M with a detection limit of 2 x 10(-7) M. The method was applied, without any interferences from the excipients, to the determination of the drug in a tablet dosage form and in drug dissolution studies. The absolute recovery for salbutamol was greater than 95% at the concentration levels studied, and reproducible voltammetric signals were obtained with a relative standard deviation of 2.4% for n = 7 at a concentration level of 8 x 10(-5) M.

Bioavailability studies of oral dosage forms containing levodopa and carbidopa using column-switching chromatography followed by electrochemical detection.

A reliable multi-dimensional column chromatographic method employing amperometric detection using a carbon fibre microelectrode procedure was used for monitoring the plasma profiles and to evaluate the pharmacokinetics and bioavailability of levodopa (L-dopa) and carbidopa (C-dopa), after ingestion of oral formulations containing these drugs. The peak currents obtained for the different analytes were directly proportional to the analyte over the concentration range 0.02-4 micrograms ml-1. Using this method, the minimum detectable concentration was estimated to be 5 and 8 ng ml-1 for L-dopa and C-dopa, respectively. Recovery studies ranged from 93.83 to 89.76%, with a relative standard deviation of less than 7%. The study was carried out in two separate weeks on five healthy non-patient fasted male/female volunteers in the age range 20-37 years and weighing between 60 kg and 78 kg. The pharmacokinetic profile of two controlled-release products containing both L-dopa and C-dopa (Sinemet CR3 and CR4) was compared on the one hand and Sinemet conventional tablets on the other. The pharmacokinetic parameters, peak concentration (Cmax), the time taken to obtain this level (Tmax), elimination half-time T1/2, elimination rate constant (Kel), plasma level ratio, fluctuation index (FI) and the area under the time-concentration curve (AUC0-8), were investigated for each individual formulation. A comparison of the uptake of L-dopa from the conventional formulation showed that L-dopa entered the plasma and achieved peak levels higher than that of the controlled release formulations. However, it showed a much higher fluctuation index and the plasma concentrations were more stable with the controlled release formulations. The data also indicated a very low accumulation of both levodopa and carbidopa following repeated administration of the drugs, which was consistent with their relatively short half-lives (less than 2 h). In contrast, the half-life for the metabolite 3-orthomethyl dopa (3-OMD) is in the order of 13 h. As a result, there was an extensive accumulation of 3-OMD and its levels were significantly higher than those of levodopa or carbidopa upon repeated administration. Urine recoveries of the three analytes over one 8 h dosing interval showed that the majority of the excreted levodopa and carbidopa was recovered during the first 4 h, and there is proportionally greater excretion of the carbidopa dose than the levodopa dose.

Analysis of terbutaline in human plasma by high-performance liquid chromatography with electrochemical detection using a micro-electrochemical flow cell.

A high-performance liquid chromatographic method is described for the determination of terbutaline in human plasma in the range 1-35 ng/ml. Detection was achieved using a carbon fibre micro-electrochemical detector and a column-switching system. The microelectrode cell has advantages over conventional glassy carbon electrode-based detection systems in that it is easy to prepare, flexible in its operation and suffers less trouble from problems such as air bubbles and leaks. Furthermore, it has a better detection limit for terbutaline (0.8 ng/ml) to that obtained using a conventional glassy carbon electrode flow detector (2 ng/ml). Sample clean-up was by on-line solid-phase extraction with column switching, providing a method which was sensitive and reproducible, where the mean overall coefficient of variation was 5.60% and drug recovery in excess of 86% at the concentration levels studied.

Simultaneous determination of salbutamol and terbutaline at overdose levels in human plasma by high performance liquid chromatography with electrochemical detection.

A multidimensional column chromatographic method involving electrochemical detection using a carbon fibre microelectrode flow cell was optimized and successfully applied to the simultaneous determination of salbutamol and terbutaline in plasma at overdose levels. This method performs, in a single step, an efficient extraction and clean-up of salbutamol and terbutaline from human plasma. The calibration graphs over three days were linear over the calibration range 20-100 ng/mL plasma with a limit of detection of 1 ng and 0.8 ng/mL plasma for salbutamol and terbutaline, respectively. The intra- and inter-assay coefficients of variation were less than 8% and the recoveries ranged from 94 to 96%. The accuracy of the assay, which was defined as the percentage difference between the mean concentration found and the theoretical concentration, was 7% or better. The proposed method combines the advantages of being simple, reproducible and selective in the presence of other sympathomimetic and commonly ingested drugs and is suitable for routine analyses to obtain valuable information about the clinical effects and treatment of overdose with these drugs. The whole procedure takes ca. 10 min and compares favourably with detection at a conventional glassy carbon electrode.