A novel ultra-high-performance supercritical fluid chromatography hyphenated to tandem mass spectrometry method for the analysis of urinary endogenous steroids in the anti-doping context.

The first step in the detection of testosterone (T) doping is to measure the urinary steroid profile for the athlete biological passport (ABP). To harmonise the analysis between anti-doping laboratories, urinary steroid profiling is parametrised in deep detail and shall be performed by gas chromatography hyphenated to mass spectrometry (GC-MS). However, due to its requirement for extensive sample preparation, alternatives to GC-MS are being actively pursued. The aim of this study was the evaluation of Ultra-High-Performance Supercritical Fluid Chromatography hyphenated to tandem Mass Spectrometry (UHPSFC-MS/MS) as an alternative for the quantification of endogenous urinary steroids. In this context, we developed a high throughput sample extraction method, followed by a novel UHPSFC-MS/MS method for the analysis of 10 endogenous urinary steroids which are relevant for doping control analysis. Depending on the steroid, the herein presented method is capable of quantification from 0.5 ng/mL up to 10 µg/mL. After validation, the applicability of the method was evaluated by analysing 132 authentic urine samples, which demonstrated results similar to classical GC-MS analysis. Steroid concentrations determined by UHPSFC-MS/MS were slightly overestimated in comparison with GC-MS, but the ratios had <10 % difference between the two methods. As the ABP considers the steroid ratios for passport evaluation, the herein presented method could be used for steroid profiling without reducing the sensitivity of the ABP. Thus, we would propose to consider UHPSFC-MS/MS as an alternative to GC-MS after more tests would have been performed to support our findings. Furthermore, we have also investigated the potential of this technology for sample purification prior to Isotope Ratio Mass Spectrometry (IRMS) for the differentiation between exogenous and endogenous origin of T and its metabolites. While the achieved separation was sufficient to purify urine samples for IRMS analysis in our proof-of-concept study, the instrumental parameters should be further refined for future use

Survey on public health risks at artisanal brick kilns in Kananga City (Central Kasaï Region), Democratic Republic of the Congo

Introduction In developing countries, diseases related to unsafe water, a lack of sanitation, and poor hygiene are important (famous) public health challenges. Purpose This study aimed to survey the public health risks at artisanal brickworks in the city of Kananga, Democratic Republic of the Congo. Methods A prospective survey was carried out among artisanal brickmakers and brickworks using questionnaires and free observation. Results The study revealed that 58% of brickyards used river water, 35% used marsh water, and 8% used pond water to shape bricks, so there was no safe water source at brick yards. Of these water sources, 84% drink unsanitary water from rivers and lakes, 23% store water in an open container, 25% drink from the source at any time when they are thirsty, 90% drink only once a day after eating or washing, 71.5% wash only once a day after working, and 5% rarely wash; 100% of people do not clean the clothes they use at work regularly; 83% of people do not have appropriate clothing for their work. They don't have boots or gloves and work with their hands and naked feet. 95.5% of bricklayers sleep in the surrounding bush. Conclusion These observations sufficiently prove that in brick factories, sanitation and hygiene measures are defective or even inadequate, and brick manufacturers are prone to various environmental diseases, of which lack of sanitation and hygiene are the main causes. This study thus highlights practices that are related to brick manufacturing, endangering public health through the contamination of drinking water and contributing to environmental problems such as deforestation. Material support, supervision of contractors for sanitation and hygiene, and health education in brick yards are recommended for promoting environmental sanitation and hygiene

Validation of high performance liquid chromatographic and spectrophotometric methods for the determination of the antiparkinson agent pramipexole dihydrochloride monohydrate in pharmaceutical products

abstract The antiparkinson agent pramipexole dihydrochloride monohydrate was quantified in pharmaceutical products by high performance liquid chromatography (HPLC) and derivative spectrophotometry. The first method was based on HPLC using tamsulosin HCl as an internal standard. In this method, chromatographic separation was achieved using a LiChrospher 60 RP column at 25°C, with a flow rate of 1.0 mL/min at 263 nm. The eluent comprised 0.01 mol/L ammonium acetate (pH 4.4) and acetonitrile (35:65 by volume). The linearity range was found to be 10.0-30.0 µg/mL with a mean recovery of 100.5 ± 1.10. The limit of detection (8 ng/mL) and limit of quantification (50 ng/mL) were calculated. In the second method, the first derivative spectrophotometric technique for the determination of pramipexole dihydrochloride monohydrate was performed by measuring the amplitude at 249 and 280 nm. In the first derivative technique, the absorbance and concentration plot was rectilinear over the 5.0-35.0 µg/mL range with a lower detection limit of 1.5 ng/mL and quantification limit of 4.5 ng/mL. The typical excipients included in the pharmaceutical product do not interfere with the selectivity of either method. The developed methods were validated for robustness, selectivity, specificity, linearity, precision, and accuracy as per the ICH and FDA guidelines (ICH Q2B, 1996; FDA,2000). In conclusion, the developed methods were successful in determining the quantity of the antiparkinson agent pramipexole dihydrochloride monohydrate in pharmaceutical products. The RSD values for the pharmaceutical product used in this study were found to be 0.97% for the HPLC method and 0.00% for the first derivative spectrophotometric method

Caratteristiche tossicologiche ed ambientali della CO2

I valori di anidride carbonica atmosferica sono in aumento secondo un trend che nel ventesimo secolo \ue8 diventato esponenziale, destando grande preoccupazione nella comunit\ue0 scientifica. Infatti, secondo gli studiosi, l\u2019aumento della CO2 atmosferica rappresenta un grave problema. L\u2019anidride carbonica \ue8 il principale responsabile (anche se non l'unico) dell\u2019effetto serra, in virt\uf9 della sua caratteristica di assorbire e trattenere la radiazione termica che la Terra emette dopo aver assorbito l\u2019energia solare; ne deriva un aumento della temperatura del pianeta, le cui conseguenze vanno dal discioglimento dei grandi ghiacci polari con conseguente aumento del livello dei mari, ad uno sconvolgimento dell\u2019intero ecosistema terrestre. Per risolvere questo problema, i leader dei paesi industrializzati nel 1997 con il Protocollo di Kyoto si sono impegnati a ridurre le emissioni dei gas serra (quali anidride carbonica, metano, ossidi nitrosi e composti fluorurati) del 5,2% rispetto ai livelli del 1990. Tuttavia, nel 2002 il livello di riduzione raggiunto dai quindici membri dell'Unione Europea che hanno ratificato l'accordo era solo del 2,9% a fronte di una riduzione del 4,8% prevista. Occorre attuare in tempi rapidi una politica energetica che impieghi sorgenti energetiche rinnovabili e non inquinanti, assieme ad opportune strategie di riduzione delle emissioni di anidride carbonica, quali adeguate procedure di stoccaggio

Therapeutic drug monitoring of recent antidepressants in patients under polypharmacy

The introduction into clinical practice of the so-called second generation antidepressants has improved the treatment of depression, since these drugs, compared to the first generation antidepressants (such as imipramine and clomipramine), show a more favourable safety profile with respect to cardiovascular effects, whilst maintaining efficacy. Nevertheless, patients treated with these newer antidepressants can present undesired effects, including serotonin syndrome, sedation, body weight changes, sexual dysfunction and suicidal ideation. Therefore, with the aim of reducing the risk for toxic/side effects, therapeutic drug monitoring (TDM) of second generation antidepressants is advisable, particularly in case of patients under polypharmacy. During the last years, a number of methods have been developed in our Laboratory for the accurate determination of antidepressant drugs and their metabolites in plasma samples obtained from patients, including drugs belonging to different classes of second-generation antidepressants (SSRI, NaSSA, SNRI). Sertraline, together with its main metabolite N-desmethylsertraline, can be analysed in plasma samples using a method based on capillary electrophoresis with laser-induced fluorescence (LIF) detection. The method employs a 488 nm wavelength laser and a sample pre-treatment procedure consisting in solid-phase extraction followed by derivatisation with fluorescein isothiocyanate. The high selectivity obtained allows the determination of sertraline in plasma samples from patients under polypharmacy. Capillary electrophoresis with diode-array detection has been employed for the enantioselective determination of mirtazapine and its active metabolite N-desmethylmirtazapine in human plasma. The method is quite fast: after a solid-phase extraction procedure, the electrophoretic run lasts 2.5 min. HPLC with fluorescence detection has been used for the determination of venlafaxine together with its main metabolite O-desmethylvenlafaxine, while HPLC coupled to UV detection was employed for the analysis of duloxetine in plasma of depressed patients

Caratteristiche tossicologiche ed ambientali della CO2

I valori di anidride carbonica atmosferica sono in aumento secondo un trend che nel ventesimo secolo è diventato esponenziale, destando grande preoccupazione nella comunità scientifica. Infatti, secondo gli studiosi, l’aumento della CO2 atmosferica rappresenta un grave problema. L’anidride carbonica è il principale responsabile (anche se non l'unico) dell’effetto serra, in virtù della sua caratteristica di assorbire e trattenere la radiazione termica che la Terra emette dopo aver assorbito l’energia solare; ne deriva un aumento della temperatura del pianeta, le cui conseguenze vanno dal discioglimento dei grandi ghiacci polari con conseguente aumento del livello dei mari, ad uno sconvolgimento dell’intero ecosistema terrestre. Per risolvere questo problema, i leader dei paesi industrializzati nel 1997 con il Protocollo di Kyoto si sono impegnati a ridurre le emissioni dei gas serra (quali anidride carbonica, metano, ossidi nitrosi e composti fluorurati) del 5,2% rispetto ai livelli del 1990. Tuttavia, nel 2002 il livello di riduzione raggiunto dai quindici membri dell'Unione Europea che hanno ratificato l'accordo era solo del 2,9% a fronte di una riduzione del 4,8% prevista. Occorre attuare in tempi rapidi una politica energetica che impieghi sorgenti energetiche rinnovabili e non inquinanti, assieme ad opportune strategie di riduzione delle emissioni di anidride carbonica, quali adeguate procedure di stoccaggio

Quality of life following a major lower limb ampu tation in Johann esburg, South Africa.

To determine the impact of lower limb amputation on qualityof life in people in the Johannesburg metropolitan area of South Africa, duringtheir reintegration to their society/community of origin.A longitudinal pre- test- post test design was utilized. Consecutive samplingwas used to recruit and interview participants (n=73) who met the inclusioncriteria. Ethical clearance was obtained. The hospitals and participants gaveinformed consent.The EQ-5D, Barthel Index, and Modified Household Economic andSocial Status Index were used to collect data. Participants were interviewed preoperatively and then followed upthree months post-operatively. Data were analysed using STATA version 10. Categorical data were analysedusing Chi-square/Fischer’s exact test and continuous data were analysed using Wilcoxon signed rank and medianregression.Most (n=21, 52.5 %) participants had no income. One participant was homeless, 17.5% (n=7) lived in shacks.The preoperative and postoperative median VAS of the EQ-5D was 60 and 70 respectively showing no significantimprovement in QOL (median EQ-5D VAS). The preoperative and postoperative median total BI score was 20 and 19respectively, showing a significant reduction in function (median total BI) three months postoperatively (p<0.001).Preoperative mobility was a predictor of postoperative quality of life. Being female was a predictor of higher qualityof life.The average EQ-5D VAS score and overall function (total BI) were generally scored high both preoperativelyand postoperatively but there was no significant improvement in EQ-5D VAS score and there was a significant reductionin function after three months. Higher scores in mobility preoperatively is a predictor of higher quality of lifepostoperatively

Iloperidone: a new benzisoxazole atypical antipsychotic drug: is it nove enough to impact the crowded atypical antipsychotic market?

Iloperidone (Zomaril\uae) is a new generation atypical antipsychotic agent, acting as a 5-HT2A/D2 antagonist, currently under development by Vanda Pharmaceuticals for the treatment of schizophrenia, bipolar disorder and other psychiatric conditions. Chemically Iloperidone is a benzisoxazole, like Risperidone, and shows a multiple receptor binding profile, sharing this feature with the other atypical antipsychotic agents. Administered orally, the drug is highly bound to plasma proteins and extensively metabolised; reduced Iloperidone is the main active metabolite. Several clinical trials were carried out, to check efficacy, safety and side effects. In order to introduce Iloperidone as an agent for the treatment of schizophrenia, a short overview of the disease and of the most important available or under development antipsychotic drugs will be reported as well. Iloperidone pharmacokinetics and pharmacodynamics are presented herein, together with an evaluation of clinical safety and efficacy results