Determination of daptomycin in human plasma and breast milk by UPLC/MS-MS

During the lactation, the choice of a proper antibiotic is crucial since the drug can cross into breast milk causing toxicity to the infant. Therefore, an extraction protocol and LC/MS-MS method for the determination of daptomycin in human milk and plasma were developed, validated and applied to a case of a breastfeeding mother affected by a purulent acute soft skin infection treated with daptomycin. Because of daptomycin high protein binding and its high molecular weight, the optimisation of the extraction protocol and analytical conditions were deeply investigated, and several parameters were taken into account: in particular the type of extraction, internal standard, the type of organic modifier, pH of the aqueous solution, and gradient. The use of a protein precipitation protocol coupled to a C8-reverse phase LC-MS/MS allows for a reliable quantification of daptomycin in both plasma (in the range of 19\u2013199 \u3bcg/mL) and breast milk (in the range of 0.12\u20130.32 \u3bcg/mL). The determination of milk/plasma (M/P) ratio, which ranged from 0.002 to 0.006, allowed to assess that daptomycin, effective for the mother, was contemporarily safe for the breastfed newborn

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

Blood cyanide determination in two cases of fatal imtoxication: comparison between headspace gas chromatography and a spectrophotometric method

Blood samples of two cases were analyzed preliminarily by a classical spectrophotometric method (VIS) and by an automated headspace gas chromatographic method with nitrogen-phosphorus detector (HS-GC \u2044 NPD). In the former, hydrogen cyanide (HCN) was quantitatively determined by measuring the absorbance of chromophores forming as a result of interaction with chloramine T. In the automated HS-GC \u2044NPD method, blood was placed in a headspace vial, internal standard (acetonitrile) and acetic acid were then added. This resulted in cyanide being liberated as HCN. The spectrophotometric (VIS) and HS-GC\u2044NPD methods were validated on postmortem blood samples fortified with potassium cyanide in the ranges 0.5\u201310 and 0.05\u20135 lg \u2044 mL, respectively. Detection limits were 0.2 lg \u2044mL for VIS and 0.05 lg \u2044mL for HS-GC\u2044NPD. This work shows that results obtained by means of the two procedures were insignificantly different and that they compared favorably. They are suitable for rapid diagnosis of cyanide in postmortem cases

A Novel Approach by SPME-GC/MS for the Determination of gammahydroxybutyric acid (GHB) in Urine Samples after Conversion into gamma-butyrolactone (GBL)

The quantitative determination of gamma-hydroxybutyric acid (GHB) in urine samples is very important to assess illicit intake or administration. To this end we evaluated several analytical methods: headspace gas-chromatography coupled to flame ionization detection (HS-GC/FID), headspace gas-chromatography coupled to mass spectrometry (HS-GC/MS), headspace gas-chromatography coupled to solid phase microextraction and mass spectrometry (HS-SPME-GC/MS). All these methods were endowed with a not sufficient sensitivity, and then we moved to solid phase microextraction coupled to gas-chromatography with mass spectrometry detection (SPME-GC/MS). At first, GHB was extracted from urine with an organic solvent and analyzed after derivatization. Under these conditions, however, there was a partial overlapping between the chromatographic peak of GHB and that of urea, also extracted by the organic solvent. Then we decided to change analytical approach and to convert GHB to gamma-butyrolactone (GBL), which is not an endogenous compound. A SPME method was optimized and validated for the determination of GBL. The limit of detection (LOD) of the method resulted to be 0.25 \u3bcg/mL for GBL, corresponding to 0.5 \u3bcg/mL for GHB. The lower limit of quantification (LLOQ) was 0.4 \u3bcg/mL for GBL and 0.8 \u3bcg/mL for GHB. The LLOQ of the method resulted 10 times lower than the endogenous level, thus allowing to distinguish between physiological conditions and exogenous assumption

Screening of new psychoactive substances (NPS)by gas-chromatography/time of flight mass spectrometry (GC/MS-TOF)and application to 63 cases of judicial seizure

A screening method for the separation and identification of more than fifty NPS is proposed. The method is based on fast gas-chromatography/time of flight mass spectrometry (FAST-GC/MS-TOF). Thanks to the shorter and narrower capillary column and to the rapid acquisition of the TOF detector a huge number of compounds are separated in a very short time of analysis (10 min). Only a few peaks were overlapped. The possibility to apply deconvolution by the software of the GC/MS-TOF instrument allowed the unequivocal identification also for the superimposed peaks. Linearity and LOD was studied and the method was applied to 63 cases of powders seized by the judicial authority at the airport of Milano Malpensa in Northern Italy in the period 2014\u20132017

Determination of polycyclic aromatic hydrocarbons in lipstick by gas-chromatography coupled to mass spectrometry: A case history

A suitable extraction protocol based on an liquid-liquid extraction with hexane/dimethyl sulfoxide and a GC/MS method were developed and validated to determine the concentration of six prohibited Polycyclic Aromatic Hydrocarbons (PAHs; benzo[a]pyrene; dibenz[a,h]anthracene; benz[a]anthracene; benzo[j]fluoranthene; benzo[k]fluoranthene; chrysene) in lipsticks commissioned by a cosmetic company to a manufacturer. The lipsticks were produced in four different colors. Analyses confirmed the presence of benz[a]anthracene and chrysene only in two colors in a concentration of 9.3\u20139.4 ng/g. The concentration of PAHs was 250 times lower than what is considered a toxic level on the basis of what reported in the litaraure and guidances for cosmetic ingredients; therefore we could assume that the risk for consumer health was negligeble

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