Major Degradation Products Research Articles

Determination of vortioxetine and its degradation product in bulk and tablets, by LC-DAD and MS/MS methods.

Vortioxetine hydrobromide (VOR), is a novel antidepressant used for the treatment of major depressive disorder. It has a chemical structure susceptible to degradation, therefore it is important to have suitable analytical methods to determine VOR in presence of its main degradation products (DP), because if the compound degrades, this could result in diminution of the therapeutic activity and safety. A simple HPLC method with photodiode array detection was developed and validated for determination of VOR in bulk and tablets, in the presence of its major DP. The drug was subjected to oxidative, hydrolytic, and photolytic stress conditions, showing significant degradation under oxidation with the formation of one DP, which was identified by ESI-MS/MS. A C18 column was used, with mobile phase consisting of acetonitrile and water with acetic acid and triethylamine in isocratic elution mode, with detection at 228 nm and 1.0 mL/min flow rate. The assay was linear in the 25-125 μg/mL concentration range. For precision, the RSD was <1.8%, the recovery was 100.0-101.6%, and the method demonstrated adequate selectivity. The method was successfully applied to quantify VOR in tablets. The results showed that the method is useful for routine analysis and for quality control purposes.

Effects of rhamnolipids on the removal of 2,4,2,4-tetrabrominated biphenyl ether (BDE-47) by Phanerochaete chrysosporium analyzed with a combined approach of experiments and molecular docking

Effects of rhamnolipids on the removal of 2,4,2,4-tetrabrominated biphenyl ether (BDE-47) by Phanerochaete chrysosporium (P. chrysosporium) had been investigated, as well as the influence of carbon source (i.e. glucose). The results showed that the removal efficiency was over 90% in all treatments in 7 d. Rhamnolipids at low concentrations (0.05 and 0.1 CMC (critical micelle concentration)) could promote the removal of BDE-47, however, the inhibition effects occurred at high concentrations (0.5 and 1.0 CMC). The further study indicated that rhamnolipids at low concentrations not only promote the growth of mycelium, but also had obvious promotion on ligninolytic enzymes activity (i.e. manganese peroxidase (MnP), lignin peroxidase (LiP) and laccase (Lac)), especially for MnP and Lac. However, the opposite effect was generated at high rhamnolipids concentrations. Meanwhile, glucose played an active role for BDE-47 removal. For better understanding the degradation mechanism, the degradation product analysis and molecular docking had been introduced to this study. The degradation product analysis indicated that OH-PBDEs were the major degradation products and hydroxylation should be the important degradation pathway. The docking results showed that the ideal binding conformation occurred between ligninolytic enzymes and BDE-47, and hydrophobic interactions were the main interaction. Moreover, hydrogen bonds and hydrophobic interactions both existed in ligninolytic enzymes and rhamnolipids interaction. That might be the reason that rhamnolipids affected enzymes activity. These results indicated that P. chrysosporium might be a type of ideal microorganisms in the removal of BDE-47 pollution, and rhamnolipids could be a type of additives for better removal efficiency.

Validated stability indicating assay method of olaparib: LC-ESI-Q-TOF-MS/MS and NMR studies for characterization of its new hydrolytic and oxidative forced degradation products

Olaparib (OLA) is a poly ADP ribose polymerase (PARP) enzyme inhibitor used to treat prostate, ovarian and breast cancer. The drug substance OLA was subjected to forced degradation as per ICH prescribed guidelines. It was degraded in hydrolytic (acidic and basic) and oxidative stress conditions and yielded four degradation products (DPs) while it remained stable in neutral hydrolytic, dry heat and photolytic stress conditions. A stability indicating assay method was developed to separate OLA and its DPs using InertSustain C18 column (250 × 4.6 mm, 5 μm) with a gradient mobile phase of 10 mM ammonium acetate (pH 4.5) and acetonitrile (ACN) at a flow rate of 1 mL min−1. The characterization of DPs was carried out by using liquid chromatography-electrospray ionization-quadrupole-time of flight tandem mass spectrometry (LC-ESI-Q-TOF-MS/MS). Major degradation products (DP-1 and DP-2) were isolated by using preparative HPLC and structures were further confirmed by using NMR spectroscopy. All the obtained DPs were new and not reported previously. The developed chromatographic method was validated as per ICH Q2 (R1) guideline and USP general chapter on method validation.

The anti-inflammatory effect of LMWF5A and N-acetyl kynurenine on macrophages: Involvement of aryl hydrocarbon receptor in mechanism of action

After a traumatic insult, macrophages can become activated leading to general inflammation at the site of injury. Activated macrophages are partially regulated by the aryl hydrocarbon receptor (AhR) which when activated suppresses inflammation by limiting the secretion of pro-inflammatory cytokines and promoting the over expression of immuno-modulatory mediators. This study aims to determine whether the low molecular weight fraction of 5% human serum albumin (LMWF5A) and N-acetyl kynurenine (NAK), an N-acetyl tryptophan (NAT) breakdown product in LMWF5A, can regulate inflammation by inhibiting macrophage activation through the AhR since kynurenine is a known AhR agonist. Using LCMS, we demonstrate that NAT is non-enzymatically degraded during accelerated aging of LMWF5A with high heat accelerating degradation. More importantly, NAK is a major degradation product found in LMWF5A. THP-1 monocytes were differentiated into macrophages using phorbol 12-myristate 13-acetate (PMA) and pre-treated with 2-fold dilutions of LMWF5A or synthetic NAK with or without an AhR antagonist (CH223191) prior to overnight stimulation with lipopolysaccharide (LPS). Treatment with LMWF5A caused a 50–70% decrease in IL-6 release throughout the dilution series. A dose-response inhibition of IL-6 release was observed for NAK with maximal inhibition (50%) seen at the highest NAK concentration. Finally, an AhR antagonist partially blocked the anti-inflammatory effect of LMWF5A while completely blocking the effect of NAK. A similar inhibitory effect was observed for CXCL-10, but the AhR antagonist was not effective suggesting additional mechanisms for CXCL-10 release. These preliminary findings suggest that LMWF5A and NAK partially promote the suppression of activated macrophages via the AhR receptor. Therefore, LMWF5A, which contains NAK, is potentially a useful therapeutic in medical conditions where inflammation is prevalent such as trauma, sepsis, and wound healing.

Five modified classical least squares based models for stability indicating analysis of cyclobenzaprine HCl with its major degradation products: A comparative study

Five modified multivariate calibration models based on classical least squares (CLS) in addition to traditional CLS model are developed and validated for assaying cyclobenzaprine HCl (CZ) with its major degradants; dibenzocycloheptatrienone (DZ) and anthraquinone (AQ), whether in its pure form or in pharmaceutical dosage form. The five models are net analyte processing CLS (NAP-CLS), orthogonal signal correction CLS (OSC-CLS), direct orthogonal signal correction CLS (DOSC-CLS) and hybrid linear analysis following the strategy of Xu and Schechter (HLA-XS) or Goicoechea et al. (HLA-GO). The five modified CLS models in addition to traditional CLS were subjected to a comparative study through manipulation of ultra-violet absorption data in the region of 220–350 nm. Three factor four level experimental design was adopted which results in 16 mixtures calibration set covering various concentrations of CZ, DZ and AQ. An extra validation set, composed of nine mixtures, was prepared for validation of the prediction power of the presented models. Experimental results showed high capability of the proposed modified CLS models for assaying CZ successfully without any interference from the co-existing degradation products (DZ and AQ). A statistical comparison between the results of CZ analysis in its dosage form by the six CLS based models and the reported HPLC method was carried out presenting no significant difference in regards to precision and accuracy. Significance of CLS based models is a consequent of their high quantitative and qualitative power for assaying multi-components mixtures.

Forced degradation of l-(+)-bornesitol, a bioactive marker of Hancornia speciosa: Development and validation of stability indicating UHPLC-MS method and effect of degraded products on ACE inhibition

The antihypertensive activity of the medicinal plant Hancornia speciosa has been previously demonstrated by us, being the activity ascribed to polyphenols and cyclitols like l-(+)-bornesitol. We herein evaluated the stability of the bioactive marker bornesitol submitted to forced degradation conditions. Bornesitol employed in the study was isolated from H. speciosa leaves. An UHPLC-ESI-MS/MS method was developed to investigate bornesitol stability based on MRM (Multiple Reaction Monitoring) acquisition mode and negative ionization mode, employing both specific (m/z 193 → 161 Da) and confirmatory (m/z 193 → 175 Da) transitions. A gradient elution of 0.1% formic acid in water and acetonitrile was performed on a HILIC column. The method was validated and showed adequate linearity (r2 > 0.99), selectivity, specificity, accuracy, and precision (RSD < 2.9%). The method was robust for deliberate variations on dessolvation temperature, but not for changes in the flow rate and dessolvation gas. The results from the stability studies allowed us to classify bornesitol as labile for acidic and alkaline hydrolysis, but as very stable for oxidative and neutral hydrolysis exposure. Bornesitol was categorized as practically stable under photolysis degradation, whereas a considerable reduction on its contents was induced by metal ions and thermolysis exposure. Degraded samples from neutral hydrolysis and thermolysis were assayed in vitro for ACE inhibition and showed a substantial decrease in biological activity as compared to intact bornesitol. myo-Inositol was identified as the major degradation products in both matrices. This is the first report on bornesitol stability under different stress conditions and the obtained data are relevant for the development and quality control of standardized products from H. speciosa leaves.

Degradation kinetics of chlorpyrifos and diazinon in volcanic and non-volcanic soils: influence of cyclodextrins.

The intensive use of insecticides such as chlorpyrifos (CPF) and diazinon (DZN) in the agricultural activities worldwide has produced contamination of soils and/or transport to non-target areas including their distribution to surface and groundwaters. Cyclodextrins (CDs) have been proposed as an alternative in remediation technologies based on the separation of contaminants from soils because they could allow a higher bioavailability for their degradation with a low environmental impact. In this work, the degradation pattern of CPF and DZN and the formation and dissipation of the major degradation products 3,5,6-trichloro-2-pyridinol (TCP) and 2-isopropyl-6-methyl-4-pyrimidinol (IMPH) was established in four agricultural volcanic and non-volcanic soils belonging to Andisol, Ultisol, and Mollisol orders. Both pesticides were highly adsorbed in these soils, consequently, with a greater probability of contaminating them. In contrast, the adsorption of their two main metabolites was low or null; therefore, they are potential groundwater contaminants. The degradation processes were studied in the natural and amended soils with β-cyclodextrin (β-CD) and methyl-β-cyclodextrin (Mβ-CD) for CPF and DZN, respectively. A slow degradation of CPF and DZN was obtained for volcanic soils with observable residues until the end of the incubation time (150-180days). In Mollisols, the higher degradation rate of CPF was favored by the neutral to basic pH, and for DZN it was related to the lower adsorption and higher bioavailability. The amendment of soils with CDs produced slower degradation rates which led to a greater concentration of the compounds at the end of the incubation time. This effect was more pronounced for DZN. The exception was the Andisol, with no significant changes for both compounds regarding the unamended soil. No residues of TCP were observed for this soil in both conditions during the whole incubation time; nevertheless, the accumulation of TCP was significant in the Ultisol and Mollisols, but the concentrations were lower for the amended soils. The accumulation of IMPH was important in Mollisol amended soils; however, their residues were observed in the volcanic soils during the whole incubation period in the natural and amended soils. An important enhancement of the microbial activity occurred in the system β-CD/CPF in Mollisols, without a more effective degradation of the insecticide. The opposite effect was observed in the system Mβ-CD/DZN mainly in the oxidative activity in all soils. The higher degradation of DZN and IMPH in natural Mollisols was related to the higher hydrolytic and oxidative activities. The stability of the inclusion complexes formed could play an important role for explaining the results obtained with the amendments.

Influence of adipic acid on the speciation of Eu(III): Review of thermodynamic data in NaCl and NaClO4 media, and a new determination of Eu-adipate complexation constant in 0.5 mol·kgw−1 NaClO4 medium by time-resolved luminescence spectroscopy

The complexation of Eu(III) by adipic acid — AdipH2, hexane-1,6-dioic acid —, one of the major hydro-soluble degradation products (HDPs) from radio-oxidized polyesterurethane, is investigated by time-resolved luminescence spectroscopy (TRLS) in NaClO4 ionic medium (0.5 mol·kgw−1). The solubility and deprotonation constants of adipic acid, as well as specific interaction theory (SIT) coefficients of aqueous AdipH2(aq) and adipate ions (AdipH− and Adip2−) were estimated using available literature data in NaCl and NaClO4 ionic media. A 1:1 (EuAdip+) complex is evidenced in TRLS with log10β(0.5 m) = 2.09 ± 0.16. Using reaction constant at another NaClO4 ionic strength from literature, the logarithm of reaction constant log10β° = 3.88 ± 0.40 at 0 ionic strength and specific ion parameter ε(EuAdip+, ClO4-) = (0.10 ± 0.40) kgw·mol−1 is estimated. This implies that adipic acid can control the Eu(III) speciation from mildly acidic to mildly basic conditions, but not in highly basic solutions characteristic of cementitious interstitial waters.

Identification of Degradant Products of Saroglitazar by UPLC Tandem Mass Spectroscopy and Attenuated Total Reflection FTIR Techniques

Abstract: Saroglitazar is a newly approved oral hypoglycemic drug by FDA. Although the drug entered the market, there are no reports on its degradation products till date. To identify the degradation products of saroglitazar during the stability studies, a RP-HPLC method was developed and validated as per ICH guidelines. The samples were eluted using acetonitrile and phosphate buffer (pH 7.4, 50:50 v/v) as a mobile phase over Kromasil 100- 5C18 (250×4.6 mm, 5μm) column. The analytes were monitored by UV detector at 294 nm with isocratic mode of elution at a flow rate of 1.0 mL/min. The stability studies were conducted under stressed conditions of acidic, basic, neutral (peroxide), photolytic studies at room temperature and thermal at 60oC for 48 hours. The stressed samples were analyzed for their degradation products by RP-HPLC. The degradant products obtained were characterized using UPLC with tandem mass spectroscopy (LC/MS/MS) and FTIR. Major degradation products were observed with m/z at 365, 247 and 294. The drug is found to be comparatively stable under photo and thermal stress. Peroxide stress has degraded the drug completely. The drug has to be stored away from oxidation during transport and storage. Key words: Saroglitazar, Degradation products, Reverse phase high performance liquid chromatography, Mass spectroscopy, Infra-red spectroscopy.

Mechanism of the Thermal Decomposition of Chlorpyrifos and Formation of the Dioxin Analog, 2,3,7,8-Tetrachloro-1,4-dioxino-dipyridine (TCDDpy).

Thermal decomposition of the pesticide, chlorpyrifos (CPf) and its major degradation product, 3,5,6-trichloro-2-pyridinol (TCpyol), has been studied by quantum chemical calculation using density functional methods at the M06-2X/GTLarge//M06-2 X/6-31+G(d,p) level of theory. Chlopyrifos was found to undergo a series of unimolecular stepwise elimination reactions releasing two molecules of ethylene and finally HOPOS to form TCpyol. TCpyol underwent oxidative decomposition initiated by abstraction of its phenolic H atom by O2. Two phenoxy radicals so produced underwent combination leading to the formation of 2,3,7,8-tetrachloro-[1,4]dioxinodipyridine (TCDDpy). Via Smiles rearrangement both cis and trans TCDDpy are formed. Kinetic models have been constructed to model the decomposition of CPf into TCpyol and of the latter into cis and trans TCDDpy. Modeled results are compared with the experiments of Sakiyama et al. ( Organohalogen Compounds, 2012, 74, 1441-1444).

PH-Dependent stability of azithromycin in aqueous solution and structure identification of two new degradation products

The degradation profile of azithromycin in buffered solutions was investigated using HPLC and found to be pH dependent in the range of 6.0–7.2. Desosaminylazitromycin, derived from hydrolytic loss of cladinose of the parent molecule, was the major degradation product at pH 6.0 but its amount progressively decreased moving toward pH 7.2. Two additional unreported degradation products were also observed and their structures were fully elucidated by MS- and NMR-spectroscopy to be associated with opening of the macrocyclic lactone ring.

Applying the hydrodistillation process to Pentadiplandra brazzeana Baill. root: a chemical assessment

A chemical study of the volatile components obtained by applying the hydrodistillation and reflux processes to Pentadiplandra brazzeana roots was performed by GC-FID and GC-MS. The hydrodistillation process showed a total yield of 0.97% with 0.11% of essential oil and 0.86% of volatile compounds from the aqueous reaction medium; in the reflux process, the volatile extract yield was 1.03%. Benzylic-type isothiocyanates were the major degradation products of glucosinolates in the essential oil (95.0%); the CH2Cl2 extracts obtained from the aqueous solutions were characterised by alcohols and amines in both processes. This study has shown that during hydrodistillation, only 10% of the glucosinolate degradation products are recovered in the essential oil whereas 90% remain in the aqueous medium, being converted into alcohols and amines. The relative percentages of the different chemical classes recovered in our experimental conditions are discussed in relation with the glucosinolate composition in the raw material.

Photocatalytic degradation of dimethoate in Bok choy using cerium-doped nano titanium dioxide.

Dimethoate, a systemic insecticide, has been used extensively in vegetable production. Insecticide residues in treated vegetables, however, pose a potential risk to consumers. Photocatalytic degradation is a new alternative to managing pesticide residues. In this study, the degradation of dimethoate in Bok choy was investigated under the field conditions using cerium-doped nano titanium dioxide (TiO2/Ce) hydrosol as a photocatalyst. The results show that TiO2/Ce hydrosol can accelerate the degradation of dimethoate in Bok choy. Specifically, the application of TiO2/Ce hydrosol significantly increased the reactive oxygen species (ROS) contents in the treated Bok choy, which speeds up the degradation of dimethoate. Ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) analysis detected three major degradation products, including omethoate, O,O,S-trimethyl thiophosphorothioate, and 1,2-Bis (acetyl-N-methyl-) methane disulfide. Two potential photodegradation pathways have been proposed based on the intermediate products. To understand the relationship between photodegradation and the molecular structure of target insecticides, we investigated the bond length, Mulliken atomic charge and frontier electron density of dimethoate using ab initio quantum analysis. These results suggest the P = S, P-S and S-C of dimethoate are the initiation sites for the photocatalytic reaction in Bok choy, which is consistent with our empirical data.

Structural Characterisation of the Stress Degradation Products of Adefovir Dipivoxil by LC-MS and NMR

Hepatitis B is one of the most common infectious disease in the world. Adefovir dipivoxil (ADL) is the recently approved drug that is prominently used in the treatment of hepatitis B. The present work focuses on the development of a stability indicating assay method for the separation and charecterization of the stress degradation products of ADL. The drug degraded under the hydrolytic (acid, alkaline and neutral) and oxidative stress conditions resulting in the formation of two degradation products. The High Performance Liquid Chromatography (HPLC) separation was achieved using C18 stationary phase (150 x 4.6 mm x 5μm) and mobile phase composed of 10 mM ammonium acetate as a buffer while acetonitrile as an organic modifier in gradient elution mode. The degradation products were characterised by tandem mass spectrometry consisting of quadrupole and time-of-flight mass analysers. The major degradation product (DP 2) of hydrolytic stress was isolated and its chemical structure was confirmed using various NMR techniques (1H, 13C, COSY, DEPT 135 and HSQC). The proposed method can be used for quantitative and qualitative determination of ADL during the process and formulation development stages.

Determination and Safety Assessment of Residual Spirotetramat and Its Metabolites in Amaranth (Amaranthus tricolor) and Soil by Liquid Chromatography Triple-Quadrupole Tandem Mass Spectrometry.

With the purpose of guaranteeing the safe use of spirotetramat and preventing its potential health threats to consumers, a QuEChERS extraction method coupled with LC triple-quadrupole tandem MS was applied in this study to determine residual spirotetramat metabolites in different tissues of amaranth (Amaranthus tricolor) and in soil. The results indicate that the spirotetramat degraded into different types of metabolites that were located in different tissues of amaranth and in soil. B-keto, B-glu, and B-enol were the three most representative degradation products in the leaf of amaranth, and B-glu and B-enol were the two major degradation products found in the stem of amaranth; however, only B-enol was detected in the root of amaranth. B-keto and B-mono were the two products detected in the soil in which the amaranth grew. The cytotoxicity results demonstrate that spirotetramat and its metabolite B-enol inhibited cellular growth, and the toxicity of spirotetramat and its metabolite B-enol exceeded than that of the metabolites B-keto, B-mono, and B-glu. This investigation is of great significance to the safe use of spirotetramat in agriculture.

Unravelling the reactivity of bifenazate in water and on vegetables: Kinetics and byproducts

In this study, we aimed to better understand the transformation mechanisms of bifenazate, a biphenyl hydrazine derivative insecticide poorly studied up to now. For this, we compared its reactivity in the dark and under simulated solar light irradiation in different media (water, non-aqueous polar solvent, surface of apolar wax films, skin of vegetable). In air-saturated pH = 5.7 water, bifenazate underwent both autoxidation in the dark (t1/2 = 34 h) and photolysis (t1/2 = 17 h). In an aprotic polar solvent such as acetonitrile, bifenazate was stable in the dark but was quickly photodegraded in the presence of oxygen (t1/2 = 2 h). The phototransformation of bifenazate was due to the oxidation of excited states by oxygen and to the cleavage of the NN bond, while the autoxidation in water started by the initial oxidation of the molecule by oxygen and involved the superoxide anion as chain carrier. On paraffinic wax film, photodegradation (t1/2 = 365 h) and dark autoxidation (t1/2 = 1600 h) were very slow. On green pepper skin, bifenazate disappeared both in the dark (t1/2 = 34 h) and through photolysis (t1/2 = 23 h) at rates close to those measured in water. This shows that on green pepper skin, bifenazate is affected by water contained in the vegetable and possibly released by transpiration. Bifenazate diazene was the major degradation product in all studied conditions. Minor byproducts were detected too. They depended on the experimental conditions showing that degradation pathways are governed by the nature and properties of the medium. In particular, on green pepper one found byproducts generated in acetonitrile and on wax by photolysis and in water by autoxidation. This finding highlights the need for a better model than wax to mimic photolysis on plant surfaces.

Degradation of p-arsanilic acid and simultaneous in-situ removal of arsenic species with ferrate(VI): Kinetics, intermediate and degradation pathway

In this study, potassium ferrate(VI) was employed for the degradation of p-arsanilic acid (p-ASA) and simultaneous removal of the generated arsenic species though in-situ coagulation. The effects of several factors, including ferrate(VI) dosage, initial pH, coexisting anions, and humic acid, on the p-ASA degradation and arsenic species removal were investigated. Under various water quality conditions, an excellent removal of p-ASA could always be achieved with the 20:1 mol radio dosage of ferrate(VI) and p-ASA within 30 min. But the removal of arsenic species is significantly affected by the water quality. It could be inhibited by alkalinity and presence of phosphate and humic acid. The generated ferric oxide was mainly 2-line ferrihydrite according to the XRD and XPS analysis. Based on the HPLC-HG-AFS and GC–MS analysis, the major degradation products were detected and the mechanism of the p-ASA degradation by ferrate(VI) and the released arsenic removal by 2-line ferrihydrite generated from ferrate(VI) was given. Two simultaneous degradation pathways of p-ASA were proposed. The p-ASA in solution attacked by ferrate(VI) in solution would lead cleavage of the As–C bond firstly to generate As(III) and p-aminophenol. On the other hand, small amounts of p-ASA initially absorbed on 2-line ferrihydrite would be firstly converted to 4-nitrophenylarsonic acid through the oxidation of –NH2 to –NO2 by ferrate(VI), subsequently transformed to As(III) and p-nitrophenol. Combined with the strong oxidizing and the high removal capacity of released arsenic by its generated product, ferrate(VI) have well potential applications for controlling the risk of p-ASA in wastewater.

Degradation kinetics and disinfection by-product formation of chlorimuron-ethyl during aqueous chlorination

Abstract The degradation kinetics of chlorimuron-ethyl during chlorination was analyzed, and the effects of the influencing factors of pH, bromide and ammonium concentrations and reaction temperature on degradation kinetics were evaluated. Regarding degradation kinetics, the chlorination of chlorimuron-ethyl followed second-order kinetics, first-order kinetics when the chlorine concentration was changed, and first-order kinetics when the chlorimuron-ethyl concentration was changed. The apparent second-order rate constant was calculated, which significantly decreased increasing pH. The rate constant of the reaction between chlorimuron-ethyl− and HOCl was calculated as 3.25 (±1.14) × 103 M−1 min−1, and under the acid-catalyzed condition, the rate constant significantly increased to 6.41 (±1.62) × 107 M−1 min−1. The degradation rate of chlorimuron-ethyl decreased with increasing bromide (at pH 5.5–7.0) and ammonium concentrations (≤6 μM). Chlorimuron-ethyl chlorination is an endothermic reaction, with an activation energy estimated as 22.46 kJ mol−1 using the Arrhenius equation. During chlorimuron-ethyl chlorination, chloroform was the major volatile degradation product during chlorimuron-ethyl chlorination, and its concentration increased with the increasing reaction time and pH level. The distribution of disinfection by-products (DBPs) formed at different solution pH levels was quite distinct. In the presence of bromide, the concentration and species of brominated DBPs increased with the increasing bromide concentration. Notably, carcinogenicity and mutagenicity of brominated DBPs were higher than their chlorinate analogs.

Gelatin versus its two major degradation products, prolyl-hydroxyproline and glycine, as supportive therapy in experimental colitis in mice.

Gelatin is an anti‐inflammatory dietary component, and its predominant metabolites entering circulation are prolyl‐hydroxyproline (Pro‐Hyp) and glycine. We evaluated the protective effects of orally administered gelatin, glycine, and Pro‐Hyp 10:3:0.8 (w/w/w) against dextran sodium sulfate (DSS)‐induced colitis in mice. According to clinical, histological, and biochemical parameters, they exhibited significant activities in the order of gelatin < glycine < Pro‐Hyp. Gelatin prevented the DSS‐induced increase in interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), and tumor necrosis factor‐α (TNF‐α) in the colon, rather than in peripheral blood. Glycine and Pro‐Hyp attenuated the DSS‐induced rise in colonic IL‐6 and TNF‐α, as well as peripheral IL‐1β, IL‐6, and TNF‐α. Hematologic results show the attenuation of DSS‐induced leukocytosis and lymphocytosis by glycine and Pro‐Hyp, rather than gelatin. These findings suggest that glycine and Pro‐Hyp constitute the material basis for gelatin's anticolitis efficacy, and they have better anticolitis activities and distinct mechanisms of action when ingested as free compounds than as part of gelatin.

Stability Study of Finasteride: Stability-Indicating LC Method, In Silico and LC-ESI-MS Analysis of Major Degradation Product, and an In Vitro Biological Safety Study.

Stability studies of the pharmaceutically important compound finasteride were conducted in order to evaluate decomposition of the drug under forced degradation conditions. A simple stability-indicating liquid chromatography method was developed and validated for the evaluation of finasteride and degradation products formed in pharmaceutical preparations and the raw material. Isocratic LC separation was achieved on a C18 column using a mobile phase of o-phosphoric acid (0.1% v/v), adjusted to pH 2.8 with triethylamine (10% v/v) and acetonitrile (52:48 v/v), with a flow rate of 1.0 mL min-1. The alkaline degradation kinetics of the drug were also evaluated and could be best described as second-order kinetics under the experimental conditions applied for the tablets and raw material. Based on in silico studies and molecular weight confirmation, a comprehensive degradation pathway for the drug and the identity of its major product could be suggested without complicated isolation or purification processes. Furthermore, a biological safety study was performed to evaluate the effect of the degraded sample in relation to the intact molecule. The results showed that the degraded sample affected the cell proliferation. Therefore, these studies show that special care must be taken during the manipulation, manufacture and storage of this pharmaceutical drug.