Determination of propofol by GC/MS and fast GC/MS-TOF in two cases of poisoning

Two cases of suspected acute and lethal intoxication caused by propofol were delivered by the judicial authority to the Department of Sciences for Health Promotion and Mother-Child Care in Palermo, Sicily. In the first case a female nurse was found in a hotel room, where she lived with her mother; four 10 mg/mL vials and two 20 mg/mL vials of propofol were found near the decedent along with syringes and needles. In the second case a male nurse was found in the operating room of a hospital, along with a used syringe. In both cases a preliminary systematic and toxicological analysis indicated the presence of propofol in the blood and urine. As a result, a method for the quantitative determination of propofol in biological fluids was optimized and validated using a liquid-liquid extraction protocol followed by GC/MS and fast GC/MS-TOF. In the first case, the concentration of propofol in blood was determined to be 8.1 \u3bcg/mL while the concentration of propofol in the second case was calculated at 1.2 \u3bcg/mL. Additionally, the tissue distribution of propofol was determined for both cases. Brain and liver concentrations of propofol were, respectively, 31.1 and 52.2 \u3bcg/g in Case 1 and 4.7 and 49.1 \u3bcg/g in Case 2. Data emerging from the autopsy findings, histopathological exams as well as the toxicological results aided in establishing that the deaths were due to poisoning, however, the manner of death in each were different: homicide in Case 1 and suicide in Case 2

Quali-Quantitative Analysis by LC/DAD and GPC of the Polyphenols ofUva Di Troia Canosina Grape Seeds for the Development of an IndustrialNutraceutical Product

The quali-quantitative determination of the principal components of "uva di Troia canosina" seed extracts by LC/ DAD analysis and the optimization of the extraction and purification processes for the development of an industrial nutraceutical product, are described. Two different fractions of seeds collected at different stages of fermentation were compared: "Tesi" 2 when there is a spontaneous stratification of the seeds at the bottom of the recipient and "Tesi" 4 at the end of fermentation. Percolation was applied and compared to maceration and the purification step carefully evaluated to obtain extracts free of contaminant species endowed with polyphenolic content comparable to commercial preparations such as Leucoselect® (Indena, SpA, Italy), Vitis Vinifera extract 95% (seeds), Vitis Vinifera dry extract 95%, Biovin grape seed and vinasse extract. (Farmalabor, Italy). In particular, "Tesi" 2 extract obtained by percolation and purified with a LLE extraction with ethyl acetate showed a polyphenolic content similar to Leucoselect®. From the quantitative analyses it was evident, as expected, that "Tesi"2 has a higher polyphenolic content compared to "Tesi" 4, because during vinification the must extracts polyphenols from the seeds. On the other hand, "Tesi" 4 is particularly convenient since it is easily obtained and very economical, being a waste product. The residual content of organic solvents (ethanol and ethyl acetate) and water was assessed in the grape extracts according to ICH rules by means respectively of HS/GC and Karl Fisher titration in order to meet the requirements for commercialization. Furthermore, the high molecular weight polyphenolic fraction of our extracts was investigated through gel permeation chromatography (GPC) and compared to that of Leucoselect®

Determination by UPLC/MS-MS of Coenzyme Q10 (CoQ10) in Plasma of Healthy Volunteers before and after Oral Intake of Food Supplements Containing CoQ10

To evaluate CoQ10 concentration a UPLC/MS-MS method for its analysis in plasma samples was developed. Before validation, the choice of the anticoagulant, of the Internal Standard (CoQ9; IS) and the stability of CoQ10 in plasma were evaluated. These determinations were necessary to assess the effect of the oral intake of CoQ10 in nine healthy volunteers after 10 days of treatment with a food supplement containing it. The basal levels of CoQ10 were determined and the analyses were repeated after four days to take into account the variability of endogenous substances. After oral intake, the increase in plasma concentration of CoQ10 resulted statistically significant (P<0.05), indicating that the assumption of food supplements containing this ubiquinone could be of help to increase its concentration, thus exploiting the its beneficial properties

Comparison between Lc/Uv and Gc/Fid techniques in determining N,NDimethylacetamide(Dma) in diacerein

Objectives: The aim of this work was the quantitative determination of N,N-Dimethylacetamide (DMA) as crystallization solvent in samples of Diacerein. DMA is commonly used as a solvent in the chemical, agricultural and pharmaceutical industries. However, in order to ensure product quality and to protect patients from the potentially toxic properties, the substances used as active ingredients in therapeutic drugs should not contain high levels of residual solvents. Methods: LC is commonly used in the pharmaceutical industry to check DMA in pharmaceutical products, but in this work we were interested in validating and comparing LC/UV and GC/FID techniques for determining the presence of DMA in Diacerein Results: Both methods showed good linearity, precision and accuracy with comparable LOD and LOQ. Conclusion: The GC method, however, since it uses DMSO as an internal standard, has higher analytical versatility, thus allowing the qualitative and quantitative determination of DMA at lower levels than those obtained with LC

Determination of propofol by GC/MS and fast GC/MS-TOF in two cases of poisoning

Two cases of suspected acute and lethal intoxication caused by propofol were delivered by the judicial authority to the Department of Sciences for Health Promotion and Mother-Child Care in Palermo, Sicily. In the first case a female nurse was found in a hotel room, where she lived with her mother; four 10 mg/mL vials and two 20 mg/mL vials of propofol were found near the decedent along with syringes and needles. In the second case a male nurse was found in the operating room of a hospital, along with a used syringe. In both cases a preliminary systematic and toxicological analysis indicated the presence of propofol in the blood and urine. As a result, a method for the quantitative determination of propofol in biological fluids was optimized and validated using a liquid-liquid extraction protocol followed by GC/MS and fast GC/MS-TOF. In the first case, the concentration of propofol in blood was determined to be 8.1 \u3bcg/mL while the concentration of propofol in the second case was calculated at 1.2 \u3bcg/mL. Additionally, the tissue distribution of propofol was determined for both cases. Brain and liver concentrations of propofol were, respectively, 31.1 and 52.2 \u3bcg/g in Case 1 and 4.7 and 49.1 \u3bcg/g in Case 2. Data emerging from the autopsy findings, histopathological exams as well as the toxicological results aided in establishing that the deaths were due to poisoning, however, the manner of death in each were different: homicide in Case 1 and suicide in Case 2

Characterization of the Volatile Components of Cannabis Preparations by Solid-Phase Microextraction Coupled to Headspace-Gas Chromatography with Mass Detector (SPME-HSGC/MS)

Solid phase microextraction coupled to headspace sampling and GC/MS technique was applied to the characterization of the volatile components of several Cannabis preparations (hashish). Different parameters of the analytical method (fiber, coating thickness, sampling and exposition temperatures, sample preparation) were evaluated to optimize the characterization of the volatile components. a-Pinene, f-myrcene, limonene, 4-carene, trans-3(10) caren-2-ol, 4,7,7-trimethylbicyclo [4.1.0] heptan-3-ol, caryophyllene, f-humulene, azulene, gurjunene, ledene and caryophyllene oxide were identified among the volatile components of all hashish preparations. Moreover, a suitable internal standard (nonane) was chosen, the reproducibility and linearity of the method were evaluated in order to carry out the quantitative determination of caryphyllene, the most abundant volatile terpene. Its quantity ranged from 800 to 3000 \ub5g/g

Determination of cyanide by microdiffusion technique coupled to spectrophotometry and GC/NPD and propofol by fast GC/MS-TOF in a case of poisoning

A man was found dead in a hotel located near Rome (Italy). The man was still holding a syringe attached to a butterfly needle inserted in his left forearm vein. The syringe contained a cloudy pinkish fluid. In the hotel room the Police found a broken propofol glass vial plus four sealed ones, an opened NaCl plastic vial and six more still sealed, and a number of packed smaller disposable syringes and needles. An opened plastic bottle containing a white crystalline powder labeled as potassium cyanide was also found. Systematic toxicological analysis (STA), carried out on blood, urine and bile, evidenced only the presence of propofol in blood and bile. So the validated L-L extraction protocol and the GC/MS-TOF method for the confirmation of propofol in the biological fluids optimized in our laboratory was applied to blood, urine and bile. The concentration of propofol resulted to be 0.432 \u3bcg/mL in blood and 0.786 \u3bcg/mL in bile. The quantitative determination of cyanide in blood was carried out by microdiffusion technique coupled to spectrophotometric detection obtaining a cyanide concentration of 5.3 \u3bcg/mL. The quantitative determination was then confirmed by GC/NPD and the concentration of cyanide resulted to be 5.5 \u3bcg/mL in blood and 1.7 \u3bcg/ mL in bile. Data emerging from autopsy findings, histopathological exams and the concentrations of cyanide suggested that death might be due to poisoning caused by cyanide, however, respiratory depression caused by propofol could not be excluded

Validation Study of Analysis of 1-Phenyl-2-Propanone in Illicit Methamphetamine Samples by Dynamic Headspace Gas Chromatography Mass Spectrometry

A new method based on dynamic headspace sampling (DHS) coupled to GC/MS analysis was developed, optimized and validated for the analysis of 1-phenyl-2-propanone (P2P) in illicit methamphetamine (MAMP) samples. The DHS parameters were investigated to reach the sensitivity suitable for this kind of analysis. The method showed of a good specificity, linearity, accuracy, precision and robustness. The analysis of ten MAMP samples seized by the judicial authority was carried out. P2P was found in all the seizure, confirming that P2P is the starting compound of the synthesis of amphetamines

Methods for the Evaluation of Polyphenolic Content in &#8216;&#8216;Uva Di Troia Canosina&#8217;&#8217; Grape and Seeds at the Different Maceration Stages

Seeds and skins derived from the small berries of \u201cuva di Troia canosina\u201d grape, a Vitis vinifera variety autochthonous of Apulia region (South Italy), collected at four different stages (\u201cTesi\u201d 1\u20134) of the fermentation process were extracted by means of a maceration. The extracts were purified and analyzed, in order to study the influence of fermentation over grape seed and skin polyphenolic content. Seed extraction was performed by amultistep maceration with two solvents: ethanol and acetone, the former giving the best results; moreover, the extracts were purified with pure ethyl acetate in order to enrich their polyphenolic content. On the other hand, skin extraction was achieved by a single-step maceration in methanol and a purification with a brominated synthetic adsorbent resin. The evaluation of the extraction yield and polyphenolic content was carried out by TLC, UV/VIS, and LC/DAD analyses. In the seed extracts, the characteristic polyphenols (catechin, epicatechin, and procyanidin B1 and B2) useful for the development of a nutraceutical product, endowed with antioxidant properties, were present, while no resveratrol was detected in \u201cuva di Troia canosina\u201d grape skin extracts, even in an LC/MS-MS analysis

Determination of 6-Monoacetyl-Morphine (6-MAM) in Brain Samples from Heroin Fatalities

Objective: Post-mortem brain samples from 15 deceased patients whose death was heroin related, were analyzed to determine 6-monoacetyl-morphine (6-MAM) concentrations. The samples belonged to people died between 2008 and 2014. The first eight samples were also analyzed in 2012 to determine only morphine and codeine levels. Method: A GC/MS method was studied in order to enhance sensitivity, thus helping the determination of 6-MAM whose detection is in most cases difficult because of the complexity of the biological matrix. The analytical method was validated using deuterated internal standards (IS-D3, morphine-D3 and codeine-D3) and it showed adequate specificity, linearity, LOD, LOQ precision and accuracy for the determination of the analyte of interest. Results: 6-MAM was evidenced only in the more recent samples, thus pointing out its low stability. Its concentration ranged from 15.6 to 28.9 ng/g. Morphine and codeine was also determined and a comparison was carried out between the blood and the brain levels of the three analytes. Moreover a parallel was established between the concentrations of morphine and codeine found in the brain in 2012 and 2015. Conclusion: 6-MAM determination in the brain is particularly important when discriminating between morphine assumption and heroin abuse. In fact in the cases in which it is not detectable in the blood it can be present in the brain. It was noticed that the concentrations of morphine found in the brain in 2015 are higher respect to the levels of 2012; a possible explanation could be that 6-MAM originally present in the brain has hydrolyzed to morphine, thus increasing its levels