Predictive analytical workflow for rapid structure elucidation and in silico toxicological qualification of an unidentified impurity in cefixime granules for oral suspension.

A novel single step solid-phase extraction combined with bromine derivatization method for rapid determination of acrylamide in coffee and its products by stable isotope dilution ultra-performance liquid chromatography tandem triple quadrupole electrospray ionization mass spectrometry

Optimisation of an extraction method for the determination of prostaglandin E2 in plasma using experimental design and liquid chromatography tandem mass spectrometry

Evaluation of different strategies to minimize the matrix effects on LC-MS/MS analysis of multiple lipophilic shellfish toxins in both acidic and alkaline chromatographic conditions

Trichoderma reesei is a mesophilic, filamentous fungus, and it is a major industrial source of cellulases, but its lignocellulolytic protein expressions on lignocellulosic biomass are poorly explored at present. The extracellular proteins secreted by T. reesei QM6a wild-type and hypercellulolytic mutant Rut C30 grown on natural lignocellulosic biomasses were explored using a quantitative proteomic approach with 8-plex high throughput isobaric tags for relative and absolute quantification (iTRAQ) and analyzed by liquid chromatography tandem mass spectrometry. We quantified 230 extracellular proteins, including cellulases, hemicellulases, lignin-degrading enzymes, proteases, protein-translocating transporter, and hypothetical proteins. Quantitative iTRAQ results suggested that the expressions and regulations of these lignocellulolytic proteins in the secretome of T. reesei wild-type and mutant Rut C30 were dependent on both nature and complexity of different lignocellulosic carbon sources. Therefore, we discuss here the essential lignocellulolytic proteins for designing an enzyme mixture for optimal lignocellulosic biomass hydrolysis.

Determination of methylmalonic acid, 2-methylcitric acid, and total homocysteine in dried blood spots by liquid chromatography-tandem mass spectrometry has usually been used as a second-tier test to improve performance of newborn screening for propionylcarnitine-related disorders. However, factors that potentially affect its detection results have not been investigated, and we aimed to evaluate these influencing factors and explore their potential utility in newborn screening and initial follow-up for propionylcarnitine-related disorders. This study comprised a prospective group (1998 healthy infants, to establish cutoff values and investigate the influencing factors) and a retrospective group (804 suspected positive cases screened from 381, 399 newborns for propionylcarnitine-related disorders by tandem mass spectrometry, to evaluate the performance of newborn screening and initial follow-up). Cutoff values for methylmalonic acid, 2-methylcitric acid, and total homocysteine were 2.12, 0.70, and 10.05 µmol/l, respectively. Concentration of methylmalonic acid, 2-methylcitric acid, and total homocysteine in dried blood spots is not impacted by sex, age, birth weight, gestational age, or dried blood spot storage time. A total of 75 of 804 cases were screened positive by combined tandem mass spectrometry and liquid chromatography-tandem mass spectrometry, thus eliminating 90% of the false positives without compromising sensitivity. Eighteen propionylcarnitine-related disorders were successfully identified, including one CblX case missed in the initial follow-up by tandem mass spectrometry. Methylmalonic acid, 2-methylcitric acid, and total homocysteine detected in dried blood spots by liquid chromatography-tandem mass spectrometry is a reliable, specific, and sensitive approach for identifying propionylcarnitine-related disorders. We recommend this assay should be performed rather than tandem mass spectrometry in follow-up for propionylcarnitine-related disorders besides second-tier tests in newborn screening.

Simultaneous determination of seven β-lactam antibiotics in human plasma for therapeutic drug monitoring and pharmacokinetic studies.

Structural annotation of small molecules in biological samples remains a key bottleneck in untargeted metabolomics, despite rapid progress in predictive methods and tools during the past decade. Liquid chromatography–tandem mass spectrometry, one of the most widely used analysis platforms, can detect thousands of molecules in a sample, the vast majority of which remain unidentified even with best-of-class methods. Here we present LC-MS2Struct, a machine learning framework for structural annotation of small-molecule data arising from liquid chromatography–tandem mass spectrometry (LC-MS2) measurements. LC-MS2Struct jointly predicts the annotations for a set of mass spectrometry features in a sample, using a novel structured prediction model trained to optimally combine the output of state-of-the-art MS2 scorers and observed retention orders. We evaluate our method on a dataset covering all publicly available reversed-phase LC-MS2 data in the MassBank reference database, including 4,327 molecules measured using 18 different LC conditions from 16 contributors, greatly expanding the chemical analytical space covered in previous multi-MS2 scorer evaluations. LC-MS2Struct obtains significantly higher annotation accuracy than earlier methods and improves the annotation accuracy of state-of-the-art MS2 scorers by up to 106%. The use of stereochemistry-aware molecular fingerprints improves prediction performance, which highlights limitations in existing approaches and has strong implications for future computational LC-MS2 developments.

The objectives of this study were to define the phenolic and fatty acid profiles, anticholinesterase, antioxidant, antimicrobial activities, and total phenolic-flavonoid contents of Lycopsis orientalis and Tragopogon latifolius var. angustifolius which have been used as food source and food supplement in Anatolia and have never been examined before. Rosmarinic and quinic acids (21.11 and 11.46 mg g–1 extract, respectively) were found to be the most abundant constituents in L. orientalis and T. latifolius var. angustifolius among the studied 27 compounds by liquid chromatography tandem mass spectrometry. In the fatty acid compositions of L. orientalis and T. latifolius var. angustifolius that were determined by gas chromatography mass spectrometry, oleic (29.1%) and palmitic (28.7%) acids were identified as the major components, respectively. The high antioxidant activity of the methanol extract of L. orientalis shows parallelism to its rosmarinic acid content. Besides, this extract showed medium anticholinesterase activity. The results of the present study proves that the L. orientalis might also be used as a food source due to its high phenolic acid content and strong antioxidant property.

The study was conducted to evaluate the applicability of ultra high-performance liquid chromatography - tandem mass spectrometry method (UHPLC-MS/MS), establish the MS/MS detection parameters and determine the validation characteristics for the analysis of residual content of avermectins in milk. The UHPLC-MS/MS method has proved to be accurate, practical and universal. This was confirmed by Decision limit (CCα) data: abamectin - 12.56 μg/kg, doramectin - 17.74 μg/kg, eprinomectin - 24.02 μg/kg, ivermectin - 12.53 μg/kg, moxidectin - 44.69 μg/kg, recovery is 88.7-110%. The data obtained for assessing the suitability, accuracy and reproducibility of the results meet the requirements of the European Directive (2002/657/EC). The efficient ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method that was developed and adopted for routine use by the laboratories of veterinary medicine, allows to detect residual quantities of 5 avermectins used in animal breeding for the prevention of helminthiases in food products including milk.

Carnitine is an endogenous quaternary amine whose primary function is to shuttle long chain fatty acids to the mitochondrial matrix, where they subsequently undergo beta oxidation. Accurate quantification of total and free carnitine is essential for the accurate diagnosis of a number of inborn errors of metabolism, including disorders of fatty acid oxidation as well as various organic acidurias. Early methods for carnitine measurement were enzyme based. Recently, liquid chromatography tandem mass spectrometry has become the method of choice for carnitine measurement. Typically, carnitine is derivitized to from a butyl ester, thus improving its ionization and retention characteristics. A potential problem with this approach is that the acidic conditions used to carry out the reaction may hydrolyze other acyl esters, resulting in ex-vivo artifacts. Consequently, we developed a hydrophobic interaction chromatography (HILIC) tandem mass spectrometry method for the quantification of carnitine. The use of HILIC allows for the derivitization step to be circumvented, while still allowing for favorable chromatographic performance. The method was shown to be accurate, precise, and robust.

Veterinary drug residues in animal-derived foods must be monitored to ensure food safety, verify proper veterinary practices, enforce legal limits in domestic and imported foods, and for other purposes. A common goal in drug residue analysis in foods is to achieve acceptable monitoring results for as many analytes as possible, with higher priority given to the drugs of most concern, in an efficient and robust manner. The U.S. Department of Agriculture has implemented a multiclass, multi-residue method based on sample preparation using dispersive solid phase extraction (d-SPE) for cleanup and ultrahigh-performance liquid chromatography-tandem quadrupole mass spectrometry (UHPLC-QQQ) for analysis of >120 drugs at regulatory levels of concern in animal tissues. Recently, a new cleanup product called "enhanced matrix removal for lipids" (EMR-L) was commercially introduced that used a unique chemical mechanism to remove lipids from extracts. Furthermore, high-resolution quadrupole-time-of-flight (Q/TOF) for (U)HPLC detection often yields higher selectivity than targeted QQQ analyzers while allowing retroactive processing of samples for other contaminants. In this study, the use of both d-SPE and EMR-L sample preparation and UHPLC-QQQ and UHPLC-Q/TOF analysis methods for shared spiked samples of bovine muscle, kidney, and liver was compared. The results showed that the EMR-L method provided cleaner extracts overall and improved results for several anthelmintics and tranquilizers compared to the d-SPE method, but the EMR-L method gave lower recoveries for certain β-lactam antibiotics. QQQ vs. Q/TOF detection showed similar mixed performance advantages depending on analytes and matrix interferences, with an advantage to Q/TOF for greater possible analytical scope and non-targeted data collection. Either combination of approaches may be used to meet monitoring purposes, with an edge in efficiency to d-SPE, but greater instrument robustness and less matrix effects when analyzing EMR-L extracts. Graphical abstract Comparison of cleanup methods in the analysis of veterinary drug residues in bovine tissues.

pH and temperature effects on the hydrolysis of three β-lactam antibiotics: Ampicillin, cefalotin and cefoxitin

Comprehensive lipid profiling of Microchloropsis gaditana by liquid chromatography - (tandem) mass spectrometry: Bead milling and extraction solvent effects

Enhanced Peptide Identification by Electron Transfer Dissociation Using an Improved Mascot Percolator

Automated detection of covalent adducts to human serum albumin by immunoaffinity chromatography, on-line solution phase digestion and liquid chromatography–mass spectrometry