Chromatography-ion Trap Mass Spectrometry Research Articles

In Vitro and Reactive Metabolites Investigation of Metabolic Profiling of Tyrosine Kinase Inhibitors Dubermatinib in HLMs by LC–MS/MS

Dubermatinib (DMB, TP-0903), a benzenesulfonamide, is an inhibitor of the tyrosine kinase AXL, which is a member of the TAM family and can prevent GAS6-mediated activation of AXL in cancer cells. Patients with previously treated chronic lymphocytic leukemia are being studied in phase I/II clinical trials to determine its antineoplastic potential (CLL). In the current work, the Xenosite web predictor tool was employed to predict the vulnerable sites of metabolism and the reactivity pathways (cyanide and GSH) of DMB. Subsequently, we present the analysis and identification of in vitro and reactive intermediates of DMB using liquid chromatography ion trap mass spectrometry (LC–ITMS). Human liver microsomes (HLMs) were exposed to dimethylbenzene in a laboratory setting, and the resulting metabolites were collected through protein precipitation. Intense reactivity toward nucleophilic macromolecules was seen in the metabolites of the piperazine and pyrimidine rings in DMB, iminium, and 2,5-quinone-imine, respectively. To assess the toxicities of the possibly reactive metabolites, DMB was incubated with HLMs in the presence of 1.0 mM KCN and 1.0 mM glutathione. The DMB metabolites found by LC–MS/MS were seven in vitro phase I metabolites, three cyano adducts, and two GSH conjugates. Phase I in vitro metabolic reactions included N-demethylation, hydroxylation, and dechlorination. DMB and its metabolites have not been investigated for their metabolism in vitro.

Phytochemical analysis and antibacterial activities of Avicennia marina (Forssk.) Vierh. extracts against Vancomycin-resistant Enterococcus faecium

Finding naturally occurring antimicrobial compounds with little danger to human health is essential since microorganisms are growing more and more resistant to antibiotics. This work evaluated ethanolic extracts of Avicennia marina (A.marina) leaves, roots, and fruits for their antibacterial efficacy against Vancomycin-Resistant Enterococcus faecium (VREF). The ethanolic extraction method was used to obtain the plant extracts. On VREF, the agar well diffusion method was utilized to test the extracts' antibacterial efficacy. On the other hand, the agar disk diffusion method was employed to examine the antibacterial effectiveness of antibiotics. For A.marina extracts, the inhibitory zone in the leaf was approximately 14.5 mm, whereas the leaf extract (Conc. 50%) had a less significant effect (10.5 mm). According to a phytochemical study, flavonoids, phenolics, triterpenes, and glycosides were found in A. marina leaf, fruit, and root extracts. Using liquid chromatography ion trap mass spectrometry (LC-IT-MS), A.marina was discovered to be a potential source of bioactive compounds with high medicinal value.

A validated and optimized method for separation and quantification of total fatty acids by gas chromatography–ion trap mass spectrometry in human plasma

Fatty acids (FAs) are associated with many physiological functions of tissues, and their alteration has been linked with tissue-specific or systemic diseases. The current situation warrants us to have a sensitive and specific method for analysis of total FAs simultaneously from the biological fluid so that the risk prediction, diagnosis or prognosis of the disease can be made effectively. Because of greater sensitivity and resolution, a method of gas chromatography-ion trap mass spectrometry (GC–IT/MS) has been optimized and validated to quantify simultaneously 19 total FAs levels in plasma and compared with GC–triple quadrupole mass spectrometry. FAs have been transesterified by methanolic acetyl chloride to fatty acid methyl esters (FAMEs). A 65 min GC method separated all 19 FAMEs. The calibration curve had good linearity up to 313–922 μM with a correlation coefficient between 0.9882 and 0.9998. The LODs and LOQs of FAMEs were in the range of 0.63 to 9.55 and 2.12 to 31.8 μM, respectively. The method has recovery up to 144 %, stability at 4 °C for 48 h and one freeze–thaw cycle, and good intra-day and inter-day precision. The optimized method has been used to quantify plasma total FAs in type 2 diabetes mellitus patients with and without acute coronary syndrome. Though a significant difference has been found between IT/MS and triple quadrupole mass spectrometry, the GC–IT/MS can help to quantify total FAs in the clinical setting.

What once was old is new again: The emergence of traditional stimulants and hallucinogens in Miami-Dade County postmortem casework

Since 2011, the Miami-Dade Medical Examiner Department (MDME) has detected over fifty different Novel Psychoactive Substances (NPS) in routine postmortem casework. On average, cases containing NPS account for 15% of the total number of cases analyzed per year at the MDME. While the incidence and variety of NPS has steadily increased in Miami in the past decade, so has the number of cases containing more traditional stimulants and hallucinogens, such as methamphetamine, methylenedioxymethamphetamine (MDMA), methylenedioxyamphetamine (MDA), lysergic acid diethylamide (LSD), and psilocin. Interestingly, this increase in prevalence of traditional stimulants and hallucinogens coincided with the beginning of the pandemic, suggesting a shift in the drug market possibly due to supply chain issues and strict travel restrictions. Screening and quantitative results from the analysis of various postmortem matrices (whole blood, liver, brain, urine, and gastric contents) were collected from 2011 to Q1 2022. All biological specimens were extracted using solid phase extraction (SPE) and screened on a routine basic drug screening method utilizing gas chromatography coupled to a nitrogen phosphorous detector and mass spectrometer (GC-NPD-MS). If needed, cases were also screened/confirmed on a sensitive, targeted method for the detection of stimulants and hallucinogens, utilizing liquid chromatography ion trap mass spectrometry (LC-Ion Trap-MS). Additionally, cases positive for methamphetamine, MDMA, and MDA were quantified utilizing liquid chromatography triple quadrupole mass spectrometry (LC-QQQ-MS). Cases were organized by year, and the data was tabulated for cases where the following analytes were reported as detected: methamphetamine, MDMA, MDA, psilocin, and LSD. Further data analysis was conducted to assess parameters such as quantitative values for the analytes of interest, additional analytes detected, cause of death (COD), manner of death (MOD), race, gender, and age. Since 2020, methamphetamine, MDMA, MDA, LSD, and psilocin have been detected in 366 postmortem cases. All targeted analytes except for LSD had a higher incidence of detection after 2019, with methamphetamine nearly tripling in the rate of detection from 2019 to 2021, and subsequently, more implicated in the cause of death for accidental overdoses. Psilocin had the largest increase in reported cases, with just one case detected in 2018, and eight cases detected in 2020 and 2021. MDMA and MDA both nearly doubled in rate of detection from 2019 to 2020. In addition, in 2020 the MDME reported its highest detected concentration of MDMA in peripheral blood, 62.5 mg/L. LSD detection remained the same, with three cases detected between 2016–2019, and three cases detected in 2020 and 2021. Methamphetamine was the most detected analyte out of the five, with 236 cases detected between 2011–2019, and 246 cases detected between 2020-Q1 2022. Of note, dimethyltryptamine (DMT) was detected for the first time in MDME casework in 2021, and TFMPP was detected in Q1 2022 for the first time since 2011. The introduction of NPS into the drug market has completely altered the landscape for forensic toxicology casework. However, with the implementation of class-wide drug scheduling and strict pandemic restrictions on air and sea travel, drugs that were not often detected in postmortem cases in Miami managed to surge in popularity and contribute to the highest rate of accidental drug overdoses recorded in the county. While monitoring NPS trends and prevalence is still necessary, it is important not to lose sight of analytes that once were considered “old news”, as there is always a possibility for them to make an impact in todays volatile drug supply.

Going deeper into the toxicokinetics of synthetic cannabinoids: in vitro contribution of human carboxylesterases

Synthetic cannabinoids (SC) are new psychoactive substances known to cause intoxications and fatalities. One reason may be the limited data available concerning the toxicokinetics of SC, but toxicity mechanisms are insufficiently understood so far. Human carboxylesterases (hCES) are widely known to play a crucial role in the catalytic hydrolysis of drugs (of abuse). The aim of this study was to investigate the in vitro contribution of hCES to the metabolism of the 13 SC 3,5-AB-5F-FUPPYCA, AB-5F-P7AICA, A-CHMINACA, DMBA-CHMINACA, MBA-CHMINACA, MDMB-4F-BINACA, MDMB-4en-PINACA, MDMB-FUBICA, MDMB-5F-PICA, MMB-CHMICA, MMB-4en-PICA, MMB-FUBINACA, and MPhP-5F-PICA. The SC were incubated with recombinant hCES1b, hCES1c, or hCES2 and analyzed by liquid chromatography–ion trap mass spectrometry to assess amide or ester hydrolysis in an initial activity screening. Enzyme kinetic studies were performed if sufficient hydrolysis was observed. No hydrolysis of the amide linker was observed using those experimental conditions. Except for MDMB-5F-PICA, ester hydrolysis was always detected if an ester group was present in the head group. In general, SC with a terminal ester bearing a small alcohol part and a larger acyl part showed higher affinity to hCES1 isozymes. Due to the low hydrolysis rates, enzyme kinetics could not be modeled for the SC with a tert-leucine-derived moiety, but hydrolysis reactions of MPhP-5F-PICA and of those containing a valine-derived moiety followed classic Michaelis–Menten kinetics. In conclusion, drug–drug/drug–food interactions or hCES polymorphisms may prolong the half-life of SC and the current results help to estimate the risk of toxicity in the future after combining them with activity and clinical data.

Development and Validation of a Rapid Method for Identification of New Synthetic Cannabinoids in Hair Based on High-Performance Liquid Chromatography-Ion Trap Mass Spectrometry Using a Simplified User Interface.

The penetration of the new psychoactive substances (NPSs) into the market of clandestine drugs is highly dynamic, causing potentially false-negative results using the current analytical instrumentation, particularly in the screening phase. At present, the suggested approach to perform a comprehensive screening requires the use of high-resolution mass spectrometry (MS) with associated high costs of purchase and maintenance and need of skilled and dedicated personnel. Here we describe the development and validation of a simplified approach based on a high-performance liquid chromatography-ion trap MS system with a user-friendly interface dedicated to toxicological analysis. The system, originally intended for a broad toxicological screening, was tuned to identify new synthetic cannabinoids in hair. After a washing step with dichloromethane, hair (about 50 mg) was incubated for 3 h with 1.5 mL ethanol. One milliliter of this solution was then dried, reconstituted with mobile phase and injected. The peak identification was based on the chromatographic retention times and MS2/MS3 data using a database which included up to 158 NPSs. The method was validated according to international guidelines on a selected panel of NPSs, namely methyl 2-[[1-(5-fluoropentyl)indazole-3-carbonyl]amino]-3,3-dimethylbutanoate (5F-ADB), 1-Pentyfluoro-1H-indole-3-carboxylic acid 8-quinolinyl ester (5F-PB 22), N-[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]-1-(5-chloropentyl)indazole-3-carboxamide (5Cl-AB-PINACA), (S)-N-(1-amino-1-oxo-3-phenylpropan-2-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide [5F-APP-PICA (PX-1)],: (R)-N-(1-amino-1-oxo-3-phenylpropan-2-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide [5F-APP-PINACA (PX-2)], N-[(2S)-1-Amino-3-methyl-1-oxobutan-2-yl]-1-(cyclohexylmethyl)indazole-3-carboxamide (AB-CHMINACA), N-[(2S)-1-Amino-3-methyl-1-oxobutan-2-yl]-1-[(4-fluorophenyl)methyl] indazole-3-carboxamid (AB-FUBINACA), methyl (2S)-2-[[1-(cyclohexylmethyl)indole-3-carbonyl]amino]-3,3-dimethylbutanoate (MDMB-CHMICA), (S)-Methyl 2-(1-(5-fluoropentyl)-1H-indole-3-carboxamido)-3-methylbutanoate (MMB-2201) and (1-pentylindol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone (UR-144). The tested analytical method showed detection limits between 0.065 and 0.125ng/mg. The intraday imprecision of the method showed average values within the range of 7.3-20%. The estimation of the trueness (bias) of method showed average values within the range of 1.5-12.3%. The analytical performance was also successfully assessed by four proficiency test samples containing NPS. No synthetic cannabinoids were detected in application to 82 hair samples from forensic cases previously analyzed with liquid chromatography-MS triple quadrupole.

Pharmacokinetics and distribution of cathine and cathinone in rats

Khat is a stimulant plant that contains stimulant chemicals such as cathine and cathinone, which abuses to induce euphoria, alertness, and motor activity. This study was carried out to determine the pharmacokinetic and distributions of cathine and cathinone following a single dosage of khat extract in rats. Practically, a total of 24 adult male Wistar albino rats aged between 8 and 12 weeks (250‐300 g weight) were randomly selected and divided into six groups 4 rats each. After a single dosage (2000 mg/kg body weight) administered by oral gavage, each group was sacrifice at specific time that schedules to be 0.5, 1, 2.5, 5, 12, and 24 hours for group number 1, 2, 3, 4, 5, and 6, respectively. Specimens were obtained as tissues and separated serum for consequences analysis. The mass spectra profiles of the interested analytes were detected by using two different types of liquid chromatography mass spectrometry; (i) Ultra‐performance liquid chromatography in coupled with with quadrupole time‐of‐flight mass spectrometry (UPLC‐QTOF/MS) system, (ii) High performance liquid chromatography ion trap mass spectrometry (HPLC‐IT/MS) system. Cathine and cathinone were qualified and quantified in serum, brain, lung, heart, liver and kidney following a single khat administration dosage. The highest tissue levels were reach within 0.5 hour in the lung, liver, and heart for cathine and within 0.5 hour in the heart for cathinone. Interestingly, more than 60% of the serum content of cathine and cathinone reached the peak in the brain within 2.5 hours with mean residence time (MRT last) 2.31 – 3.31 hours. Moreover, at the level of the neurotransmitters such as epinephrine, dopamine, norepinephrine and serotonin, their presence were detected in a delayed, prolonged and organ specific manner. This findings provided further basis for experimental, clinical, and forensic studies.

A Validated and Optimized Method for Separation and Quantification of Fatty Acids by Gas Chromatography–Ion Trap Mass Spectrometry in Human Plasma

A Validated and Optimized Method for Separation and Quantification of Fatty Acids by Gas Chromatography–Ion Trap Mass Spectrometry in Human Plasma

"Source-Induced Dissociation Vs Collision-Induced Dissociation Fragmentation Behavior of Four Antiviral Drugs in a Liquid Chromatography Ion-Trap Mass Spectrometry"

Mass spectrometry (MS) is an important tool for analyzing or detecting a wide range of organic, inorganic, natural, unnatural molecules, especially drugs, proteins, peptides are of interests beside routine analysis..

Urinary Bisphenol A Concentrations and Parameters of Ovarian Reserve among Women from a Fertility Clinic.

Background: Human exposure to environmentally widespread endocrine disruptors, especially bisphenol A (BPA), has been suggested to affect reproductive health. Animal studies indicate that BPA may play a role in the process of reproduction and impact on maturing oocytes, meiotic cell division or fertilization rate. Nevertheless, data regarding the effects of exposure to BPA on women’s ovarian function are still limited. Therefore, the aim of the current study is to assess the effects of environmental exposure to BPA on ovarian reserve. Methods: The study participants consisted of 511 women in reproductive age (25–39 years) who attended an infertility clinic for diagnosis, due to the couples’ infertility. BPA urinary concentrations were assessed by the validated gas chromatography ion-trap mass spectrometry method. The ovarian reserve was assessed using ovarian reserve parameters: Hormones concentrations: E2 (estradiol), FSH (follicle stimulating hormone), AMH (anti-Müllerian hormone), and AFC (antral follicle count). Results: In the present study, the negative association between BPA urinary concentrations and AMH (p = 0.02) and AFC (p = 0.03) levels was found. Exposure to BPA was not related to other examined parameters of ovarian reserve (FSH, E2). Conclusions: Our results suggest that BPA exposure may affect women ovarian reserve parameters and reduce ovarian reserve. As this is one of the first studies of its kind, the findings need confirmation in a further investigation.

Clinical utility of validated gas chromatography–ion trap mass spectrometry in patients with anticholinesterase pesticides poisoning

Intentional or unintentional intake of anticholinesterase pesticides became common due to their extensive use in agricultural and domestic purposes, resulting in numerous poisoning cases. A simple, accurate, and sensitive gas chromatography-ion trap mass spectrometry-based method for the quantification of 12 anticholinesterase pesticides (monocrotophos, dimethoate, dichlorvos, azinphos-methyl, carbofuran, chlorpyrifos, dialifos, diazinon, malathion, parathion, methidathion, and terbufos) in serum was developed, and its utility in patients with alleged pesticides poisoning was assessed. The quantification was performed using liquid-liquid extraction by toluene/chloroform (4:1,v/v) with 500 μL of serum. On column limit of detection and limit of quantification were less than 50.00 μg/L. The recovery ranged from 97.54 to 103.23%. The calibration curves were linear (R2 > 0.9937). Accuracy was found to be between – 7.1 and 7.2%. Intra-day and inter-day reproducibility was less than 17% for the spiked quality control serum samples. The level of pesticide in serum quantified by the validated method correlated with clinical signs and symptoms, pseudo-cholinesterase activity, total atropine dose, length of hospital stay, and clinical outcome in 15 patients with alleged pesticide poisoning. The validated method may be used for monitoring and prognosis in patients with pesticide poisoning and diagnosis of poisoning in forensic toxicology.

Identification of Erectile Dysfunction Drugs in Dietary Supplements by Liquid Chromatography Ion Trap Mass Spectrometry

With the rise in consumption of dietary supplements for various ailments such as erectile dysfunction (ED), there is concern that these supplements may contain illegally added phosphodiesterase type 5 (PDE-5) inhibitor and its analogs. HPLC or LC is a general separation method, and MS is a detection technique, together LC/MS/MS technology provides the mass spectral confirmation in identifying sildenafil, vardenafil, tadalafil and their analogs. In our present study, a sample extraction technique with 1:1 acetonitrile: water solvents and sonication was used for screening, then identification was performed using an LC coupled with Velos Pro linear ion trap mass spectrometry. This was a simple and reliable method for a variety of matrices of dietary supplements and pharmaceutical formulations in tablet, capsule or liquid form. The run time is only 6.5 min, allowing for a quick screening and identification of all of analytes of ED drugs using full scan and data-dependent scan MS/MS, except for tadalafil and aminotadalafil (MS/MS/MS). To conclude this study, Sildenafil, tadalafil, vardenafil, and other 16 analogs in dietary supplements could be quickly screened and identified by HPLC coupled with ion trap MS using data dependent scanning function. The main method using the short column is very rapid, and saves a lot of running time and solvents, and the identification is further confirmed by MS/MS information. The current study develops and validates a quick and reliable method to screen for ED drugs.

Pharmacokinetic analysis of atractylenolide III in rat plasma after oral administration of Atractylodes japonica rhizome extract by ultra-performance liquid chromatography-ion trap mass spectrometry

Atractylenolide III is one of the major bioactive compounds in Atractylodes japonica rhizome; it has been used clinically for the treatment of gastrointestinal disorders. In the present study, a simple, rapid, and selective analytical method was developed and validated for the quantification of atractylenolide III in rat plasma samples using ultra-performance liquid chromatography–ion trap mass spectrometry (UPLC–ion trap MS). Liquid–liquid extraction with ethyl acetate was used for plasma sample preparation. Bergapten was used as an internal standard (IS). The separation of compounds was carried out on a C18 column, with isocratic elution of 0.1% formic acid in water–acetonitrile (45:55, v/v) at 35 °C. Mass detection was performed in the positive ion mode, under optimized conditions for an electrospray ionization source at m/z 249.1 for atractylenolide III and m/z 217.0 for the IS. The methods of instrumental analysis and plasma sample extraction were validated in terms of precision, accuracy, matrix effect, and extraction recovery, with acceptable values. The present method was successfully applied to the pharmacokinetic study of atractylenolide III in rat plasma samples after oral administration of A. japonica rhizome extract.

In vivo and in vitro metabolism of the novel synthetic cannabinoid 5F-APINAC

New generations of synthetic cannabinoids (SCs) have recognized strong psychoactive effects, rapidly becoming potent drugs of abuse. Characterization of metabolites associated with SCs is useful for their subsequent detection in biological samples. We aimed to investigate the metabolism of 5F-APINAC, a novel SC, in human liver microsomes (HLMs) (in vitro) and in a rat model (in vivo). For the in vitro study, the standard solution of 5F-APINAC was incubated with HLMs for 1 h at 37 °C. In the in vivo study, rats received 15 mg/kg of 5F-APINAC diluted in ethanol or in dimethyl sulfoxide, while a vehicle control group received placebo. Urine was collected 3, 6, and 24 h after administration. The metabolic characterization was performed using liquid chromatography–ion trap mass spectrometry and liquid chromatography–quadrupole time-of-flight mass spectrometry. In total, 15 metabolites associated with 5F-APINAC were tentatively identified. The metabolites were classified as: 1-adamantol metabolites, oxidative defluorination metabolites, and N-fluoropentylindazole-3-carboxylic acid metabolites. The modifications included ester hydrolysis, mono-, di-, and trihydroxylation of adamantyl ring and N-fluoropentylindazole moiety, oxidation (carbonyl formation) of the N-fluoropentyl side chain, oxidative loss of fluorine, and glucuronidation, as well as combinations thereof. The predominant metabolic reaction was ester hydrolysis in both in vitro and in vivo experiments and formation of M9 (5-fluoropentylindazole-3-carboxylic acid). However, the most recommendable metabolites for proving 5F-APINAC consumption in urine were M4.1, M7, and M13. No metabolites were detected in rat’s urine 24 h after drug administration. The discovered metabolites are proposed to be incorporated into routine screening analytical methods as the urine markers of 5F-APINAC consumption. This is the first report to demonstrate the metabolism of 5F-APINAC to our knowledge.

A new aerosol flow reactor to study secondary organic aerosol

Abstract. Gas-particle equilibrium partitioning is a fundamental concept used to describe the growth and loss of secondary organic aerosol (SOA). However, recent literature has suggested that gas-particle partitioning may be kinetically limited, preventing volatilization from the aerosol phase as a result of the physical state of the aerosol (e.g. glassy, viscous). Experimental measurements of diffusion constants within viscous aerosol are limited and do not represent the complex chemical composition observed in SOA (i.e. multicomponent mixtures). Motivated by the need to address fundamental questions regarding the effect of the physical state and chemical composition of a particle on gas-particle partitioning, we present the design and operation of a newly built 0.3 m3 continuous-flow reactor (CFR), which can be used as a tool to gain considerable insights into the composition and physical state of SOA. The CFR was used to generate SOA from the photo-oxidation of α-pinene, limonene, β-caryophyllene and toluene under different experimental conditions (i.e. relative humidity, VOC and VOC∕NOx ratios). Up to 102 mg of SOA mass was collected per experiment, allowing the use of highly accurate compositional- and single-particle analysis techniques, which are not usually accessible due to the large quantity of organic aerosol mass required for analysis. A suite of offline analytical techniques was used to determine the chemical composition and physical state of the generated SOA, including attenuated total reflectance infrared spectroscopy; carbon, hydrogen, nitrogen, and sulfur (CHNS) elemental analysis; 1H and 1H-13C nuclear magnetic resonance spectroscopy (NMR); ultra-performance liquid chromatography ultra-high-resolution mass spectrometry (UHRMS); high-performance liquid chromatography ion-trap mass spectrometry (HPLC-ITMS); and an electrodynamic balance (EDB). The oxygen-to-carbon (O∕C) and hydrogen-to-carbon (H∕C) ratios of generated SOA samples (determined using a CHNS elemental analyser) displayed good agreement with literature values and were consistent with the characteristic Van Krevelen diagram trajectory, with an observed slope of −0.41. The elemental composition of two SOA samples formed in separate replicate experiments displayed excellent reproducibility, with the O∕C and H∕C ratios of the SOA samples observed to be within error of the analytical instrumentation (instrument accuracy ±0.15 % to a reference standard). The ability to use a highly accurate CHNS elemental analyser to determine the elemental composition of the SOA samples allowed us to evaluate the accuracy of reported SOA elemental compositions using UHRMS (a commonly used technique). In all of the experiments investigated, the SOA O∕C ratios obtained for each SOA sample using UHRMS were lower than the O∕C ratios obtained from the CHNS analyser (the more accurate and non-selective technique). The average difference in the ΔO∕C ratios ranged from 19 % to 45 % depending on the SOA precursor and formation conditions. α-pinene SOA standards were generated from the collected SOA mass using semi-preparative HPLC-ITMS coupled to an automated fraction collector, followed by 1H NMR spectroscopy. Up to 35.8±1.6 % (propagated error of the uncertainty in the slope of the calibrations graphs) of α-pinene SOA was quantified using this method; a considerable improvement from most previous studies. Single aerosol droplets were generated from the collected SOA samples and trapped within an EDB at different temperatures and relative humidities to investigate the dynamic changes in their physiochemical properties. The volatilization of organic components from toluene and β-caryophyllene SOA particles at 0 % relative humidity was found to be kinetically limited, owing to particle viscosity. The unconventional use of a newly built CFR, combined with comprehensive offline chemical characterization and single-particle measurements, offers a unique approach to further our understanding of the relationship between SOA formation conditions, chemical composition and physiochemical properties.

A Method Validation for Simultaneous Determination of Phthalates and Bisphenol A Released from Plastic Water Containers

Phthalates (or phthalate esters, PAEs) and bisphenol A (BPA) are widely used in various industries, particularly in the fields of cosmetics and packaging, and they increase the malleability and workability of materials. As a result of their use, some international health organizations have begun to study them. In this study, the authors developed a methodology for the simultaneous determination of dimethyl phthalate (DMP), diethyl phthalate (DEP), diisobutyl phthalate (DiBP); dibutyl phthalate (DBP), bis(2-ethylhexyl) phthalate (DEHP); di-n-octyl-phthalate (DnOP) and bisphenol A (BPA) from drinking and non-potable waters. The extraction of PAEs and BPA was performed using a solvent-based dispersive liquid–liquid microextraction (SB-DLLME) method. The analytical determination was performed using a gas chromatography–ion trap mass spectrometry (GC-IT/MS) analysis. The entire procedure was validated as recoveries were studied according to the volume and the extraction solvent used, pH, and ionic strength. Dynamic linearity ranges and linear equations of all the compounds were experimentally determined as well as the limit of detection (LOD) (1–8 ng mL−1) and the limit of quantification (LOQ) (5–14 ng mL−1), reproducibility, and sensitivity. The method was applied to 15 water samples (mineral water and tap water) for determining PAEs and BPA released from the plastic container. After the release simulation, four PAEs (i.e., DiBP, DBP, DHEP, and DnOP) were determined at very low concentrations (below 1.2 ng mL−1) in two water samples from (sport) bottles.

Identification of Widespread Antibiotic Exposure in Patients With Cholera Correlates With Clinically Relevant Microbiota Changes.

BackgroundA first step to combating antimicrobial resistance in enteric pathogens is to establish an objective assessment of antibiotic exposure. Our goal was to develop and evaluate a liquid chromatography–ion trap mass spectrometry (LC/MS) method to determine antibiotic exposure in patients with cholera.MethodsA priority list for targeted LC/MS was generated from medication-vendor surveys in Bangladesh. A study of patients with and those without cholera was conducted to collect and analyze paired urine and stool samples.ResultsAmong 845 patients, 11% (90) were Vibrio cholerae positive; among these 90 patients, analysis of stool specimens revealed ≥1 antibiotic in 86% and ≥2 antibiotics in 52%. Among 44 patients with cholera and paired urine and stool specimens, ≥1 antibiotic was detected in 98% and ≥2 antibiotics were detected in 84%, despite 55% self-reporting medication use. Compared with LC/MS, a low-cost antimicrobial detection bioassay lacked a sufficient negative predictive value (10%; 95% confidence interval, 6%–16%). Detection of guideline-recommended antibiotics in stool specimens did (for azithromycin; P = .040) and did not (for ciprofloxacin) correlate with V. cholerae suppression. A nonrecommended antibiotic (metronidazole) was associated with decreases in anaerobes (ie, Prevotella organisms; P < .001).ConclusionThese findings suggest that there may be no true negative control group when attempting to account for antibiotic exposure in settings like those in this study.

Elucidation of diazinon metabolites in rice plants by liquid ‎chromatography ion-trap mass spectrometry

ABSTRACTA fast, selective and sensitive reversed-phased liquid chromatography coupled to ion-trap mass spectrometry has been developed to elucidate and confirm the diazinon metabolites with a wide range of polarity in the rice plant samples. Sample extraction and purification were performed with a QuEChERS-based (Quick, Easy, Cheap, Effective, Rugged, and Safe) procedure. To boost all metabolism sensitivities, all rice extracts were concentrated under vacuum to near dryness and taken up into initial mobile phase. Careful optimisation of the LC–MS/MS parameters were achieved in order to attain a fast separation with the best sensitivity. The detection was carried out on an ion-trap mass spectrometer by electrospray ionisation in positive ion mode (ESI+) with multiple reaction monitoring.

Analytical Method Validation for Determining Organophosphorus Pesticides in Baby Foods by a Modified Liquid–Liquid Microextraction Method and Gas Chromatography–Ion Trap/Mass Spectrometry Analysis

Baby food is made specifically for babies between the ages of 4/6 months up to 2 years, and it comes in multiple varieties and tastes. This paper proposes a protocol for a rapid and reliable determination of 19 organophosphorus pesticides (OPs) by means of a method based on ultrasound-vortex-assisted liquid–liquid microextraction coupled with a gas chromatography–ion trap mass spectrometry (UVALLME–GC-IT/MS). The method development starts from the extraction solvent evaluation, i.e., n-heptane; the solution, held for 5 min on the vortex mixer and for 6 min in an ultrasonic bath to 100 W for favoring the solvent dispersion and the determinant extraction, is centrifuged at 4000 rpm for 30 min: 1 μL of the organic extract is injected into the GC-IT/MS. All the analytical parameters investigated are deeply discussed; LODs/LOQs (0.2–1.3 and 0.5–2.9 ng/g) and recoveries (81–109%) are compared with other papers dealing the determination of OPs in baby food matrix. The whole method has been applied to real commercial freeze-dried and soft baby food samples: the results do not show any significant contaminant values.

Impact of storage time and temperature on volatomic signature of Tinta Negra wines by LLME/GC-ITMS

The current study reports the effect of storage temperature, storage time and glucose content on the volatomic signature of Tinta Negra wines using liquid-liquid microextraction (LLME) combined with gas chromatography–ion trap mass spectrometry (GC–ITMS). A total of 65 volatile organic compounds (VOCs) were identified in Tinta Negra, of which only 14 appear during storage. Based on the results, the freshness and fruitiness odours that are related to the presence of some varietal and fermentative components (e.g. terpenic compounds, esters) are lost during wine storage, while other descriptors such as caramel, dried fruit, spice, toast and wood arise due to Maillard reactions (e.g. furanic compounds), among other chemical reactions (e.g. lactones). The results obtained in this study may be applied as a useful tool in the winemaking field in order to introduce changes in the baking (estufagem) process and/or predict the effects of storage time when applying high temperatures. In addition, the VOCs identified in this study may help winemakers and wine chemists better understand the aroma composition and profile of Tinta Negra wines.