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Pharmaceutics May 2024Indoxyl sulfate (IxS) and -cresyl sulfate (CS) are toxic uremic compounds with documented pathological outcomes. This review critically and comprehensively analyzes the... (Review)
Review
Liquid Chromatography-Mass Spectrometry Analytical Methods for the Quantitation of -Cresol Sulfate and Indoxyl Sulfate in Human Matrices: Biological Applications and Diagnostic Potentials.
Indoxyl sulfate (IxS) and -cresyl sulfate (CS) are toxic uremic compounds with documented pathological outcomes. This review critically and comprehensively analyzes the available liquid chromatography-mass spectrometry methods quantifying IxS and CS in human matrices and the biological applications of these validated assays. Embase, Medline, PubMed, Scopus, and Web of Science were searched until December 2023 to identify assays with complete analytical and validation data (N = 23). Subsequently, citation analysis with PubMed and Scopus was utilized to identify the biological applications for these assays (N = 45). The extraction methods, mobile phase compositions, chromatography, and ionization methods were evaluated with respect to overall assay performance (e.g., sensitivity, separation, interference). Most of the assays focused on human serum/plasma, utilizing acetonitrile or methanol (with ammonium acetate/formate or formic/acetic acid), liquid-liquid extraction, reverse phase (e.g., C18) chromatography, and gradient elution for analyte separation. Mass spectrometry conditions were also consistent in the identified papers, with negative electrospray ionization, select multiple reaction monitoring transitions and deuterated internal standards being the most common approaches. The validated biological applications indicated IxS and/or CS were correlated with renal disease progression and cardiovascular outcomes, with limited data on central nervous system disorders. Methods for reducing IxS and/or CS concentrations were also identified (e.g., drugs, natural products, diet, dialysis, transplantation) where inconsistent findings have been reported. The clinical monitoring of IxS and CS is gaining significant interest, and this review will serve as a useful compendium for scientists and clinicians.
PubMed: 38931865
DOI: 10.3390/pharmaceutics16060743 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Alectinib HCl (ALBHCl) is a tyrosine kinase inhibitor used for non-small cell lung carcinoma (NSCLC). The aim of this study is to unlock some of the physicochemical...
Alectinib HCl (ALBHCl) is a tyrosine kinase inhibitor used for non-small cell lung carcinoma (NSCLC). The aim of this study is to unlock some of the physicochemical properties of ALBHCL that serve as a database for any future studies. A solubility study of ALBHCL was performed in different solvents. Also, photostability was tested in the solution and solid states, and the order of reaction and rate constant were calculated. In addition to the pH solubility relation, the pH-rate relation at different temperatures was also studied, and the profiles were constructed. A solubility study was also performed in different media for the purpose of optimizing suitable sink conditions for the in vitro dissolution testing of solid dosage forms. Solubility tests in multiple solvents and pH conditions revealed that the highest solubility was in DMSO, methanol, and chloroform, with acidic media yielding the maximum solubility but degrading at rather low pH levels. ALBHCL proved unstable at high temperatures and under light exposure, with varying stability across different pH levels. The optimal dissolution media for in vitro oral dosage form evaluation were determined, achieving sink conditions at pH levels of 6.8 and 4.5 with specific additives. This study enhances the existing database on ALBHCL's physicochemical properties, emphasizing the importance of pH optimization in pharmaceutical processes and providing valuable insights into its pharmaceutical application.
PubMed: 38931444
DOI: 10.3390/ph17060776 -
Pharmaceuticals (Basel, Switzerland) Jun 2024() is a shrub of the Andean Altiplano of Bolivia, Chile and Peru, consumed by local communities as a traditional medicine for several maladies such as diabetes, hepatic...
() is a shrub of the Andean Altiplano of Bolivia, Chile and Peru, consumed by local communities as a traditional medicine for several maladies such as diabetes, hepatic and inflammatory diseases. is rich in mulinane- and azorellane-type diterpenoids. For two of these, acute hypoglycemic effects have been described, but the impact of diterpenoids on fatty liver disease has not been investigated. Therefore, organic fractions were prepared using petroleum ether, dichloromethane and methanol. Their content was characterized by UHPLC/MS, revealing the presence of ten diterpenoids, mainly mulinic acid, azorellanol and mulin-11,13-diene. Next, mice fed with a high-fat diet (HFD), a model of metabolic dysfunction-associated fatty liver disease (MAFLD), received one of the fractions in drinking water for two weeks. After this treatment, hepatic parameters were evaluated. The fractions did not reduce hyperglycemia or body weight in the HFD-fed mice but increased the serum levels of hepatic transaminases (AST and ALT), reduced albumin and increased bilirubin, indicating hepatic damage, while histopathological alterations such as steatosis, inflammation and necrosis generated by the HFD were, overall, not ameliorated by the fractions. These results suggest that organic extracts may generate hepatic complications in patients with MAFLD.
PubMed: 38931413
DOI: 10.3390/ph17060746 -
Pharmaceuticals (Basel, Switzerland) May 2024Mebendazole () is a benzimidazole carbamate anthelmintic used worldwide for the treatment and prevention of parasitic disorders in animals and humans. A large number of...
Mebendazole () is a benzimidazole carbamate anthelmintic used worldwide for the treatment and prevention of parasitic disorders in animals and humans. A large number of in vivo and in vitro studies have demonstrated that also has anticancer activity in multiple types of cancers. After oral administration, the phenylketone moiety of is rapidly reduced to the hydroxyl group to form the chiral hydroxy metabolite (). To the best of our knowledge, there is no information in the literature on the stereochemical course of transformation and the anthelmintic and antitumor activity of individual enantiomers of . In the present study, we describe in detail the direct HPLC resolution of on a 100 mm × 4.6 mm Chirapak IG-3 column packed with 3 μm silica particles containing amylose (3-chloro-5-methylphenylcarbamate) as a selector. At 25 °C and using pure methanol as the mobile phase, the enantioseparation and resolution factors were 2.38 and 6.13, respectively. These conditions were scaled up at a semi-preparative scale using a 250 mm × 10 mm Chiralpak IG column to isolate multi-milligram amounts of both enantiomeric forms of the chiral metabolite. The chiroptical properties of the collected enantiomers were determined and, through a theoretical study, were related to the more stable conformations of MBZ-OH. The first and second eluted enantiomers were dextrorotatory and levorotatory, respectively, in dimethylformamide solution. Finally, by recording the retention factors of the enantiomers as the water content in the water-acetonitrile mobile phases was progressively varied, U-shaped retention maps were generated, indicating a dual and competitive hydrophilic interaction liquid chromatography and reversed-phase liquid chromatography retention mechanism on the Chirapak IG-3 chiral stationary phase.
PubMed: 38931363
DOI: 10.3390/ph17060696 -
Plants (Basel, Switzerland) Jun 2024In response to the global rise in antibiotic resistance and the prevalence of bacterial biofilm-related infections, the antibacterial efficacy of methanolic, ethanolic,...
In response to the global rise in antibiotic resistance and the prevalence of bacterial biofilm-related infections, the antibacterial efficacy of methanolic, ethanolic, and aqueous extracts of 18 Lamiaceae plants from Serbia was evaluated. The total coumarins and triterpenes were detected spectrophotometrically, while a microdilution assay measured their effects on bacterial growth. Additionally, the impact of these extracts was assessed on PAO1 adhesion and invasion in human fibroblasts and biofilm formation and degradation. The alcoholic extracts had the highest phytochemical content, with and being the richest in coumarins and triterpenes, respectively. Gram-positive bacteria, particularly , were more susceptible to the extracts. ethanolic and methanolic extracts inhibited bacterial growth the most efficiently. Although the extracts did not inhibit bacterial adhesion, most ethanolic extracts significantly reduced bacterial invasion. and ethanolic extracts significantly inhibited biofilm formation, while extract was the most active in biofilm degradation. This study significantly contributes to the literature by examining the antibacterial activity of Lamiaceae extracts, addressing major literature gaps, and underscoring their antibacterial potential, particularly and ethanolic extracts, linking their efficacy to coumarins and triterpenes.
PubMed: 38931048
DOI: 10.3390/plants13121616 -
Molecules (Basel, Switzerland) Jun 2024The abuse and irrational use of tetracyclines (TCs) in human medicine and animal husbandry has become a serious concern, affecting the ecological environment and human...
Rapid Determination of Tetracyclines in Drinking and Environmental Waters Using Fully Automatic Solid-Phase Extraction with Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry.
The abuse and irrational use of tetracyclines (TCs) in human medicine and animal husbandry has become a serious concern, affecting the ecological environment and human health. The aim of this study was to develop a sensitive and selective method using fully automatic solid-phase extraction coupled with ultra-performance liquid chromatography-tandem mass spectrometry for the determination of twelve TCs in water. Four isotope-labeled internal standards for TCs were used to correct matrix effects. Several parameters affecting extraction efficiency were systematically optimized, and the optimum experimental conditions found were 1.0 L water sample with 0.5 g/L NaEDTA (pH 3.0) extracted and enriched by CNW HLB cartridge and eluted by 4 mL of acetone:methanol (/, 1:1). The enrichment factors were up to 798-1059 but only requiring about 60 min per six samples. Under the optimized conditions, the linearity of the method ranged from 0.2 to 100 μg/L for 12 TCs, the detection limits were as low as 0.01-0.15 ng/L, and the recoveries were in the range of 70%-118%, with relative standard deviations less than 15%. The developed method can be successfully utilized for the determination of 12 TCs in pure water, tap water, river water, and mariculture seawater. In summary, three and six TCs were detected in river water and mariculture seawater, respectively, with total concentrations of 0.074-0.520 ng/L (mean 0.248 ng/L) and 0.792-58.369 ng/L (12.629 ng/L), respectively. Tetracycline (TC) and oxytetracycline (OTC) were the dominant TCs in river water, while doxytetracycline (DXC) and OTC were dominant in mariculture seawater.
Topics: Tandem Mass Spectrometry; Solid Phase Extraction; Tetracyclines; Water Pollutants, Chemical; Drinking Water; Chromatography, High Pressure Liquid; Limit of Detection
PubMed: 38930985
DOI: 10.3390/molecules29122921 -
Molecules (Basel, Switzerland) Jun 2024Sulforaphane is a chiral phytochemical with chemopreventive properties. The presence of a stereogenic sulfur atom is responsible for the chirality of the natural...
Green HPLC Enantioseparation of Chemopreventive Chiral Isothiocyanates Homologs on an Immobilized Chiral Stationary Phase Based on Amylose tris-[()-α-Methylbenzylcarbamate].
Sulforaphane is a chiral phytochemical with chemopreventive properties. The presence of a stereogenic sulfur atom is responsible for the chirality of the natural isothiocyanate. The key role of sulfur chirality in biological activity is underscored by studies of the efficacy of individual enantiomers as chemoprotective agents. The predominant native () enantiomer is active, whereas the () antipode is inactive or has little or no biological activity. Here we provide an enantioselective high-performance liquid chromatography (HPLC) protocol for the direct and complete resolution of sulforaphane and its chiral natural homologs with different aliphatic chain lengths between the sulfinyl sulfur and isothiocyanate group, namely iberin, alyssin, and hesperin. The chromatographic separations were carried out on the immobilized-type CHIRALPAK IH-3 chiral stationary phase with amylose tris-[()-methylbenzylcarbamate] as a chiral selector. The effects of different mobile phases consisting of pure alcoholic solvents and hydroalcoholic mixtures on enantiomer retention and enantioselectivity were carefully investigated. Simple and environmentally friendly enantioselective conditions for the resolution of all chiral ITCs were found. In particular, pure ethanol and highly aqueous mobile phases gave excellent enantioseparations. The retention factors of the enantiomers were recorded as the water content in the aqueous-organic modifier (methanol, ethanol, or acetonitrile) mobile phases progressively varied. U-shaped retention maps were generated, indicating a dual and competitive hydrophilic interaction liquid chromatography (HILIC) and reversed-phase liquid chromatography retention mechanism on the CHIRALPAK IH-3 chiral stationary phase. Finally, experimental chiroptical studies performed in ethanol solution showed that the () enantiomers were eluted before the () counterpart under all eluent conditions investigated.
Topics: Isothiocyanates; Chromatography, High Pressure Liquid; Stereoisomerism; Amylose; Green Chemistry Technology
PubMed: 38930960
DOI: 10.3390/molecules29122895 -
Molecules (Basel, Switzerland) Jun 2024L. (Apiaceae) is a medicinal plant with a well-documented history in phytotherapy. The aim of the present work was to isolate isopimpinellin (5,8-methoxypsoralen; IsoP)...
L. (Apiaceae) is a medicinal plant with a well-documented history in phytotherapy. The aim of the present work was to isolate isopimpinellin (5,8-methoxypsoralen; IsoP) from the fruit of this plant and evaluate its biological activity against selected tumor cell lines. The methanol extract obtained with the use of an accelerated solvent extraction (ASE) method was the most suitable for the quantitative analysis of coumarins in the fruit matrix. The coumarin content was estimated by RP-HPLC/DAD, and the amount of IsoP was found to be 404.14 mg/100 g dry wt., constituting 24.56% of the total coumarin fraction (1.65 g/100 g). This, along with the presence of xanthotoxin (368.04 mg/100 g, 22.36%) and bergapten (253.05 mg/100 g, 15.38%), confirmed fruits as an excellent source of these compounds. IsoP was isolated (99.8% purity) by combined liquid chromatography/centrifugal partition chromatography (LC/CPC) and tested for the first time on its antiproliferative activity against human colorectal adenocarcinoma (HT29, SW620), osteosarcoma (Saos-2, HOS), and multiple myeloma (RPMI8226, U266) cell lines. MTT assay results (96 h incubation) demonstrated a dose- and cell line-dependent decrease in cell proliferation/viability, with the strongest effect of IsoP against the Saos-2 cell line (IC50; 42.59 µM), medium effect against U266, HT-29, and RPMI8226 (IC50 = 84.14, 95.53, and 105.0 µM, respectively), and very weak activity against invasive HOS (IC50; 321.6 µM) and SW620 (IC50; 711.30 µM) cells, as well as normal human skin fibroblasts (HSFs), with IC50; 410.7 µM. The mechanistic study on the Saos-2 cell line showed that IsoP was able to reduce DNA synthesis and trigger apoptosis via caspase-3 activation. In general, IsoP was found to have more potency towards cancerous cells (except for HOS and SW620) than against healthy cells. The Selective Index (SI) was determined, underlining the higher selectivity of IsoP towards cancer cells compared to healthy cells (SI = 9.62 against Saos-2). All these results suggest that IsoP might be a promising molecule in the chemo-prevention and treatment of primary osteosarcoma.
Topics: Humans; Fruit; Cell Line, Tumor; Furocoumarins; Plant Extracts; Ammi; Cell Proliferation; Antineoplastic Agents, Phytogenic; Apoptosis; Chromatography, High Pressure Liquid; Cell Survival
PubMed: 38930940
DOI: 10.3390/molecules29122874 -
Molecules (Basel, Switzerland) Jun 2024A promising method was established for the determination of nine halobenzoquinones (HBQs) in potable water by membrane solid-phase extraction (MSPE) pretreatment and the...
A promising method was established for the determination of nine halobenzoquinones (HBQs) in potable water by membrane solid-phase extraction (MSPE) pretreatment and the liquid chromatography-mass spectrometry (LC-MS) method. A 500 mL water sample was taken for enrichment by the SDB-RPS membrane, which was previously activated by methanol and ultrapure water. The sample was eluted with methanol and re-dissolved with the initial mobile phase after nitrogen blowing. Then, it was detected in negative ion mode using the working curve, and HBQs were quantified by the external standard method. The linearity was satisfactory in the concentration range of 4-1000 ng/L, with correlation coefficients of 0.9963~0.9994. The recoveries were 73.5~126.6% at three spiked levels, with relative standard deviations (RSDs) of 6.8~15.5%. The limits of detection (LOD, S/N = 3) values were 0.1~0.7 ng/L. The results demonstrate that the MSPE-LC-MS method is reliable, rapid, and sensitive for the simultaneous analysis of nine HBPs in potable water.
Topics: Solid Phase Extraction; Chromatography, Liquid; Benzoquinones; Drinking Water; Mass Spectrometry; Limit of Detection; Water Pollutants, Chemical; Liquid Chromatography-Mass Spectrometry
PubMed: 38930920
DOI: 10.3390/molecules29122856 -
Molecules (Basel, Switzerland) Jun 2024Organic phosphoester (OPE) antioxidants are currently required due to their contribution to enhancing the quality of polymers, including polypropylene (PP). In this...
Organic phosphoester (OPE) antioxidants are currently required due to their contribution to enhancing the quality of polymers, including polypropylene (PP). In this research, an integral methodology is presented for the efficient extraction of bis(2,4-dicumylphenyl) pentaerythritol diphosphite from industrial wastewater. Upon employing the solid-phase extraction (SPE) technique, the recovered compound is subjected to a comprehensive analysis of the recovered compound using high-performance liquid chromatography (HPLC), mass spectrometry (MS), thermal analysis (TGA), Fourier transforms infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). Subsequently, purified Bis(2,4-dicumylphenyl) pentaerythritol diphosphite was evaluated as a thermo-oxidative stabilizer after incorporation into PP resins. The relative standard deviation (RSD), Error (Er), linearity (R), and percentage (%) recovery were less than 2.6, 2.5, more significant than 0.9995, and greater than 96%, respectively, for the inter-day and intra-day tests of the chromatographic method and the SPE. Except for chloroform, which was necessary due to the solubility properties of the investigated analyte, the use of environmentally friendly solvents, such as methanol and acetonitrile, was considered during the development of this research. The OPE extracted from industrial wastewater was characterized by FTIR, UV-Vis, DSC, TGA, and MS, allowing the elucidation of the structure of Bis(2,4-dicumylphenyl) pentaerythritol diphosphite (BDPD). The recovered OPE was mixed with PP resins, allowing it to improve its thermal properties and minimize its thermo-oxidative degradation. Organophosphorus flame retardant (OPE)' concentration in wastewater is alarming, ranging from 1179.0 to 4709.6 mg L. These exceed toxicity thresholds for aquatic organisms, emphasizing global environmental risks. Using a validated solid-phase extraction (SPE) technique with over 94% recovery, the study addresses concerns by removing organic contaminants and supporting circular economy principles. The high economic and environmental significance of recovering BDPD underscores the need for urgent global attention and intervention.
PubMed: 38930844
DOI: 10.3390/molecules29122780