Applications Of LC-MS Research Articles

Applications of liquid chromatography-mass spectrometry based metabolomics in predictive and personalized medicine.

Metabolomics is a fast-developing technique used in biomedical researches focusing on pathological mechanism illustration or novel biomarker development for diseases. The ability of simultaneously quantifying thousands of metabolites in samples makes metabolomics a promising technique in predictive or personalized medicine-oriented researches and applications. Liquid chromatography-mass spectrometry is the most widely employed analytical strategy for metabolomics. In this current mini-review, we provide a brief update on the recent developments and novel applications of LC-MS based metabolomics in the predictive and personalized medicine sector, such as early diagnosis, molecular phenotyping or prognostic evaluation. COVID-19 related metabolomic studies are also summarized. We also discuss the prospects of metabolomics in precision medicine-oriented researches, as well as critical issues that need to be addressed when employing metabolomic strategy in clinical applications.

Current trends in isotope-coded derivatization liquid chromatographic-mass spectrometric analyses with special emphasis on their biomedical application.

Currently, LC-MS has various applications in different areas such as metabolomics, pharmacokinetics, and pathological studies. Yet, matrix effects resulting from co-existing constituents remain a major problem for LC-MS [or LC-tandem mass spectrometry (LC-MS/MS)]. Moreover, technical problems and instrumental drifts may lead to ion abundance variance. Thus, an internal standard (IS) is required to guarantee the accuracy and precision of the method. Because of their limited number, isotope-coded derivatization (ICD) has been recently introduced to overcome this problem. For ICD, a stable heavy isotope-coded moiety is used for labeling the standard or the control sample and the formed products can act as ISs. A light form of the reagent is used for labeling the sample. Then, both are mixed and analyzed by LC-MS(/MS). This strategy permits the identification of different unknown analytes including potential metabolites and disease biomarkers. All these attributes lead to persistent growth in the applications of ICD LC-MS(/MS) in various biomedical branches. In this article we review the ICD methods published in the last eight years for biomedical applications as well as briefly summarize other applications for environmental and food analyses as some of their used ICD reagents were further applied for analyzing biological specimens or have the potential for that.

Anthocyanin Profiling Using UV-Vis Spectroscopy and Liquid Chromatography Mass Spectrometry

As a powerful antioxidant and natural colorant, anthocyanins are being used increasingly as a component of food supplements and nutraceutical products. Hence, its characterization is a prerequisite for further exploration of its nutraceutical potential. UV-Vis and MS are the two important techniques, which have been largely employed for the qualitative and quantitative determination of anthocyanins. However, a comprehensive review of the applications of these techniques in literature is scarce. This paper aims to review the utilization of UV-Vis spectral data as well as mass spectral data for characterization and putative identification of anthocyanins with approaches of quantification. The techniques described in literature have been thoroughly reviewed and comparatively evaluated. The complementary approaches of UV-Vis and MS spectra have been discussed for identification and quantification of these compounds. Valuable information about the chemical composition and structure of anthocyanins can be predicted from the UV-Vis spectral data, such as number and type of glycosylation as well as absence or presence of acylation, to name a few. It is also pointed out that for their structural confirmation, selectivity of mass detectors with unit and high-resolution analysis could be effective. The combination of LC-MS with UV-Vis spectroscopy provides complementary information on structural details of anthocyanins. In case the analytical reference standards are available, a triple quadrupole mass spectrometer provides selectivity and quantitative sensitivity in analysis. On the other hand, high-resolution MS analysis provides valuable information for tentative identification during nontarget screening of compounds when the reference standard is not available. This paper reviews the applications of UV-Vis spectroscopy and LC-MS for qualitative and quantitative analysis of anthocyanins.

Metabolomic Strategies Involving Mass Spectrometry Combined with Liquid and Gas Chromatography.

Amongst all omics sciences, there is no doubt that metabolomics is undergoing the most important growth in the last decade. The advances in analytical techniques and data analysis tools are the main factors that make possible the development and establishment of metabolomics as a significant research field in systems biology. As metabolomic analysis demands high sensitivity for detecting metabolites present in low concentrations in biological samples, high-resolution power for identifying the metabolites and wide dynamic range to detect metabolites with variable concentrations in complex matrices, mass spectrometry is being the most extensively used analytical technique for fulfilling these requirements. Mass spectrometry alone can be used in a metabolomic analysis; however, some issues such as ion suppression may difficultate the quantification/identification of metabolites with lower concentrations or some metabolite classes that do not ionise as well as others. The best choice is coupling separation techniques, such as gas or liquid chromatography, to mass spectrometry, in order to improve the sensitivity and resolution power of the analysis, besides obtaining extra information (retention time) that facilitates the identification of the metabolites, especially when considering untargeted metabolomic strategies. In this chapter, the main aspects of mass spectrometry (MS), liquid chromatography (LC) and gas chromatography (GC) are discussed, and recent clinical applications of LC-MS and GC-MS are also presented.

LC-MS of oligonucleotides: applications in biomedical research.

Recent findings have elucidated numerous novel biological functions for oligonucleotides. Current standard methods for the study of oligonucleotides (i.e., hybridization and PCR) are not fully equipped to deal with the experimental needs arising from these new discoveries. More importantly, as the intracellular capacity of oligonucleotides is being harnessed for biomedical applications, alternative bioanalytical techniques become indispensable in order to comply with ever-increasing regulatory requirements. Owing to its ability to detect oligonucleotides independent of their sequence, LC-MS is emerging as the analytical method of choice for oligonucleotides. In this article, the current applications of LC-MS in the analysis of oligonucleotides, with an emphasis on RNA therapeutics and biomarkers, will be examined. In addition, the theoretical framework of oligonucleotide ESI is carefully inspected with the purpose of identifying the contributing factors to MS signal intensity.

Microfluidic chip‐based liquid chromatography coupled to mass spectrometry for determination of small molecules in bioanalytical applications: An update

Many microfluidic chip-based LC-MS systems have been utilized for high-throughput analysis in various fields of bioanalytical applications such as proteomic, glycomic, pharmaceutical, and clinical research. This review is an update of a previous review article (Electrophoresis 2012, 33, 635-643) to mainly cover the most recent advancements in chip-based LC-MS for determining small molecules in bioanalysis. First, the different types of microfluidic chip devices for chip-based LC-MS analysis will be discussed. Following the discussion of the recent developments in the chip-based instrumentation, the applications of chip-based LC-MS for determining small molecules, such as glycans, pharmaceutical drugs, drugs of abuse, drug metabolites, and biomarkers in various biological sample matrixes will also be included in this review.

Microfluidic chip‐based liquid chromatography coupled to mass spectrometry for determination of small molecules in bioanalytical applications

The development and integration of microfabricated liquid chromatography (LC) microchips have increased dramatically in the last decade due to the needs of enhanced sensitivity and rapid analysis as well as the rising concern on reducing environmental impacts of chemicals used in various types of chemical and biochemical analyses. Recent development of microfluidic chip-based LC mass spectrometry (chip-based LC-MS) has played an important role in proteomic research for high throughput analysis. To date, the use of chip-based LC-MS for determination of small molecules, such as biomarkers, active pharmaceutical ingredients (APIs), and drugs of abuse and their metabolites, in clinical and pharmaceutical applications has not been thoroughly investigated. This mini-review summarizes the utilization of commercial chip-based LC-MS systems for determination of small molecules in bioanalytical applications, including drug metabolites and disease/tumor-associated biomarkers in clinical samples as well as adsorption, distribution, metabolism, and excretion studies of APIs in drug discovery and development. The different types of commercial chip-based interfaces for LC-MS analysis are discussed first and followed by applications of chip-based LC-MS on biological samples as well as the comparison with other LC-MS techniques.

Biomarker Analysis for Prostate Cancer Diagnosis Using LC–MS and CE–MS

Prostate cancer is one of the most common cancer types in men. In addition, it is the second leading cause of cancer death in the USA and Canada. Prostate cancer diagnosis is not a precise science yet. Discovery of potential biomarkers for early prostate cancer diagnosis and monitoring is crucially important. LC-MS and CE-MS have been widely used analytical techniques in the biomarker discovery. This review will describe the applications of LC-MS with different ionization techniques, such as ESI, atmospheric-pressure photoionization and atmospheric-pressure chemical ionization, and CE-MS techniques used in prostate cancer biomarker analysis.

Recent Advances in Characterization of Impurities - Use of Hyphenated LC-MS Technique

Profiling of impurities in pharmaceutical products is an important part of the pharmaceutical manufacturing process and it is a regulatory expectation. Impurities may influence the safety and efficacy of the pharmaceutical products. Estimation of the impurity of pharmaceuticals provides excellent means for drug authorities to control the manufacturing process. To meet the challenges and to build high degree of purity in drug substances and drug products, it is required to carry out all the investigations for standards of drugs and impurities to get significant results. Different methods are available for impurity profiling; the most common analytical methods are based upon spectroscopic and chromatography separation techniques. One of the powerful tools of impurity profile is liquid chromatography (LC) coupled with mass spectroscopy (MS), and it is employed for the identification of impurities, natural products, drug metabolites, and proteins. LC-MS offers selectivity and specificity in both the chromatographic separation and detection steps, and is found as necessary steps to measure compounds at extremely low concentrations. LC-MS is steadily applied to scrutinize impurity during pharmaceutical product development and manufacturing process to support the safety evaluation of batches used in clinical studies. In this review, strategies for impurity profiling of pharmaceuticals with the applications of LC-MS, LCMS/ MS, LC-ESI/MS and LC-TOF/MS methods will be critically reviewed and discussed. Keywords: Impurities, Impurity profiling, Liquid chromatography, mass spectrometry, Hyphenated LC, MS, LC-MS/MS, Identification, Characterization, Hyphenated LC-MS Technique, spectroscopic, chromatography separation techniques, liquid chromatography (LC), mass spectroscopy (MS), LC-ESI/MS, LC-TOF/MS, active pharmaceutical ingredients, ICH (International Conferences on Harmonization, ICH Q3A(R), Q3B(R), detectors, stationary phases, NMR, LC column, LCMS/ MS, chemical ionization (APCI), electrospray ionization (ESI) modes, (HPLC)-MS, capillary electrophoresis, capillary electrochromatography, ionization, LC-methods with ultra violet (UV), UV chromatogram, ion-current, (m/z ratio), mobile phase, mobile- phase additives, buffer or ion-pair reagent, electrospray, nebulizing gas pressure, cone voltage, molecular fingerprint, multiple reaction monitoring (MRM), fragmentation (MS), hybrid quadrupole/ time-of-flight (TOF), LC-MSn/TOF instrument, Pantoprazole sodium, 5-(difluoromethoxy)-2, dimethoxy-2, pyridinyl)methyl]sulfinyl]-1H, benzimidazole, Cefdinir, Ceftizoxime sodium, Rizatriptan benzoate, Piperacilin, Piperaquine, 2D NMR spectroscopy, 1-[(5-chloroquinolin-4)-piperazinyl]-3-[(7-chloroquinolin-4)-piperazinyl] propane, Simvastatin, Fluconazole, Ezetimibe, Avermectins, pazoapanib hydrochloride, VEGFR tyrosine kinase inhibitor, genotoxic impurities, pazopanib, Pantoprazole sodium bulk, alkyl esters of sulfonates, trimethylamine, Sulfonic acids, Methanesulfonic, benzenesulfonic, ptoluenesulfonic, sulfuric acids, (DAD) detection, simvastatin molecule, NIDDM, 2-(4-hydroxybenzyl)-N, 5-bis-(4- fluorophenyl)-5-hydroxypentanamide, Cefadroxil, Diacerein, reverse-phase preparative liquid chromatography, isocratic, clindamycin palmitate hydrochloride, RPHPLC-MS, TOF/MS analyzer, clindamycin

Applications of LC-MS in PET Radioligand Development and Metabolic Elucidation

Positron emission tomography (PET) is a very sensitive molecular imaging technique that when employed with an appropriate radioligand has the ability to quantititate physiological processes in a non-invasive manner. Since the imaging technique detects all radioactive emissions in the field of view, the presence and biological activity of radiolabeled metabolites must be determined for each radioligand in order to validate the utility of the radiotracer for measuring the desired physiological process. Thus, the identification of metabolic profiles of radiolabeled compounds is an important aspect of design, development, and validation of new radiopharmaceuticals and their applications in drug development and molecular imaging. Metabolite identification for different chemical classes of radiopharmaceuticals allows rational design to minimize the formation and accumulation of metabolites in the target tissue, either through enhanced excretion or minimized metabolism. This review will discuss methods for identifying and quantitating metabolites during the pre-clinical development of radiopharmaceuticals with special emphasis on the application of LC/MS.

New Insight on the Construction of Bioeffect Fingerprint of Traditional Chinese Medicine —— Integration with Microfluidic Chip Technique

With the advancement of analytical measures of traditional Chinese medicine(TCM) and information technology,chemical composition-based fingerprint of TCM has become an important quality control method.However,how to combine chemical fingerprint with bioeffect fingerprint online to reflect the quality of TCM more comprehensively to some extent is still a key scientific issue in modern TCM research.The present paper introduces the applications of LC-MS,LC-NMR for the detailed analysis of chemical fingerprint,and microfluidic chip technology on the biological activity detection,analyzes the feasibility of the combination of microfluidic chip technology with fingerprint of chemical composition.Hopefully,it can promote and facilitate the quality research of TCM.

Applications of LC-MS to quantitation and evaluation of the environmental fate of chiral drugs and their metabolites

This review provides a brief overview on chirality as a structural characteristic of pharmaceuticals. This property has received very little attention in the field of environmental analysis, despite the fact that many drugs are marketed as racemates. The review covers the different methodologies commercially available on chiral liquid chromatography (LC) columns to provide good resolving power. It also reviews recent results obtained in chiral analysis of drugs and their metabolites with an array of modern mass-spectrometric analyzers coupled to an LC system that provides high selectivity and sensitivity. It further covers the occurrence and the fate of chiral drugs in the environment.

Applications of LC-MS in Toxicology

Applications of LC-MS in Toxicology

Applications of LC-MS in the study of the uptake, distribution, metabolism and excretion of bioactive polyphenols from dietary supplements

Specific and quantitative analyses of the bioactive components and their metabolites in body fluids are essential to assess the interaction between groups of compounds in dietary supplements and preparations of psychoactives. Reverse-phase LC separations combined with tandem mass spectrometry provide the necessary specificity and sensitivity. In this paper, applications of these methods are described for the analysis of isoflavones, salvinorin A, synephrine isomers and their metabolites in serum, urine and aqueous humor.

The use of liquid chromatography-atmospheric pressure ionization-mass spectrometry in water analysis – Part I: Achievements

Liquid chromatography-mass spectrometry using atmospheric pressure ionization is dramatically changing the analytical methods, potential and tasks of water analysis. The present status in applying this technique to organic as well as inorganic water constituents and its use in the context of wastewater treatment and drinking water preparation is reviewed. Separation techniques such as reversed-phase HPLC, ion chromatography, capillary electrophoresis and size-exclusion chromatography are also considered. LC-MS is well established to detect industrial mass chemicals such as dyes, aromatic sulfonates, surfactants and complexing agents but also trace compounds such as drugs, endocrine-disrupting compounds, toxins, phenols and haloacetic acids. The applications of LC-MS are now expanding towards the analysis of inorganic compounds such as oxo-anion. The success in characterizing natural organic matter by LC-MS is still limited, but an interesting potential is seen in detecting organometallic complexes as well as non-covalently bound adducts following electrospray ionization.

The use of liquid chromatography-mass spectrometry for the identification of drug degradation products in pharmaceutical formulations.

Recent applications of LC-MS in the analysis of drug degradation products in pharmaceutical formulations are reviewed. Drug degradation products are categorized according to their formation mechanism: oxidation, hydrolysis, dimerization and adduct formation with excipients and packaging materials. The oxidative ring opening and dimerization of an indole derivative are discussed in detail. The examples used in this review clearly demonstrate that LC-MS is a very powerful technique for the analysis of low-level degradates in formulations without the time-consuming isolation process. At the same time, limitations and precaution of using LC-MS techniques for unknown identification are also addressed. In some cases, the LC-MS data could become misleading if the ionization process and gas-phase behavior of the analytes are not well understood.

Environmental applications of thermospray LCMS: Qualitative analysis of sulfonated azo dyes

Environmental applications of thermospray LCMS: Qualitative analysis of sulfonated azo dyes