GC‐MSn and LC‐MS/MS couplings for the identification of degradation products resulting from the ozonation treatment of Acetochlor

The degradation of the chloracetamide herbicide acetochlor has been studied under simulated ozonation treatment plant conditions. The degradation of acetochlor included the formation of several degradation products that were identified using GC/ion‐trap mass spectrometry with EI and CI and HPLC/electrospray‐QqTOF mass spectrometry. Thirteen ozonation products of acetochlor have been identified. Ozonation of the deuterated herbicide combined to MSⁿ and high‐resolution mass measurement allowed effective characterization of the degradation products. At the exception of one of them, the product B (2‐chloro‐2', ethyl‐6', methyl‐acetanilide), none of the identified degradation products has been already reported in the literature. Post‐ozonation kinetics studies revealed that the concentrations of most degradation products evolved noticeably with time, particularly during the first hours following the ozonation treatment. This raises concerns about the fate of degradation products in the effluents of treatment plants and suggests the need for a better control on these products if their toxicity was demonstrated. Copyright © 2012 John Wiley & Sons, Ltd.     

HPLC-DAD-MSn to investigate the photodegradation pathway of nicosulfuron in aqueous solution

The environmental interest of sulfonylurea herbicides was derived from the possibility of diffusion and penetration of these herbicides in the deepest layers of the ground, in particular in sandy or clay-poor soils, up to the ground waters; another interest of the study is their natural degradation pathway which leads to the formation of new species that are potentially more toxic and stable than the precursor herbicides. In this case, a lower persistence in the environment unfortunately does not correspond to a lower toxicity: hence, the importance of the identification of the species can be potentially formed. Here, nicosulfuron, a typical sulfonylurea herbicide, is considered in order to outline the environmental fate of the molecules generating from the simulation of one of the natural processes that can occur, i.e. photoinduced degradation. Aqueous nicosolfuron solutions underwent a simulated sun irradiation: the new species formed during the degradation process were identified by HPLC-DAD-MS/MS and a degradation pathway was proposed. The effect of temperature and the contribution of the hydrolysis were also evaluated. The use of ESI in both positive ion (PI) and negative ion (NI) mode and APCI in PI mode permits to obtain integrated information about the transformation products that can form; moreover, a study of the total ion chromatogram followed by the extraction of the SIM chromatograms of the most intense m/z signals made possible the identification of five possible photodegradation transformation products.     

Characterization of intermediate compounds formed upon photoinduced degradation of quinolones by high-performance liquid chromatography/high-resolution multiple-stage mass spectrometry

The paper deals with the photocatalytic transformation of two antibacterial agents, ofloxacin and ciprofloxacin, under simulated solar irradiation using titanium dioxide as photocatalyst. The investigation involved monitoring decomposition of the drugs, identifying intermediate compounds, assessing mineralization, and evaluating the toxicity of drug derivatives. High-resolution mass spectrometry was employed to assess evolution of the photocatalyzed process over time. Respectively 15 and 8 main species were identified after transformation of ofloxacin and ciprofloxacin. Through the full analysis of MS and MSn spectra and a comparison with parent drug fragmentation pathways, the different isomers were characterized. In the ofloxacin molecule, the initial transformation attacks are confined to the piperazine moiety and to the methyl groups, while the fluoroquinolone core is unmodified. Conversely, ciprofloxacin degradation involves two parts of the molecule: the piperazinic moiety and the quinolone moiety. All these intermediates are easily degraded and by 4 h mineralization is complete. Toxicity assays using Vibrio fischeri prove that neither ciprofloxacin nor its intermediates exhibit acute toxicity. In ofloxacin the secondary degradation products exhibit toxicity; a correlation exists between the evolution of the intermediate compounds and the toxicity connected to them.     

Poly(methyl malate) nanoparticles: formation, degradation, and encapsulation of anticancer drugs

PMLA nanoparticles with diameters of 150-250 nm are prepared, and their hydrolytic degradation is studied under physiological conditions. Degradation occurs by hydrolysis of the side chain methyl ester followed by cleavage of the main-chain ester group with methanol and L-malic acid as the final degradation products. No alteration of the cell viability is found after 1 h of incubation, but toxicity increases significantly after 3 d, probably due to the noxious effect of the released methanol. Anticancer drugs temozolomide and doxorubicin are encapsulated in the NPs with 20-40% efficiency, and their release is monitored using in vitro essays. Temozolomide is fully liberated within several hours, whereas doxorubicin is steadily released from the particles over a period of 1 month.     

Simultaneous Enantiomeric Separation of Carfentrazone-Ethyl Herbicide and Its Hydrolysis Metabolite Carfentrazone by Cyclodextrin Electrokinetic Chromatography. Analysis of Agrochemical Products and a Degradation Study

The different activity and toxicity that the enantiomers of agrochemicals may have requires the development of stereoselective analytical methodologies enabling the individual determination of each enantiomer. The aim of this work was to develop the first Electrokinetic Chromatography methodology enabling the simultaneous enantiomeric separation of carfentrazone-ethyl herbicide and its hydrolysis metabolite carfentrazone. The use of an anionic cyclodextrin as chiral selector (captisol at 2.5% (w/v)) in a 25 mM acetate buffer, at a temperature of 30 °C, and an applied voltage (reverse polarity) of −30 kV, allowed the simultaneous separation of the four enantiomers of the two compounds studied in 6.8 min with enantiomeric resolutions of 5.0 for carfentrazone-ethyl and 5.1 for carfentrazone. Analytical characteristics of the developed method were evaluated and found adequate to achieve the quantitation of carfentrazone-ethyl and carfentrazone. Analysis of a commercial herbicide formulation showed the potential of the method for the quality control of these agrochemical products. Degradation studies for carfentrazone-ethyl revealed that no significant degradation took place in cleaned sand samples while a significant but not stereoselective degradation took place in soils for the whole period of time considered (seven days).     

Discerning the stability behaviour of mavacamten availing liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy: In silico toxicity and mutagenicity prediction of degradation products

The present study aimed to separate, identify, and characterise the degradation products formed when mavacamten is exposed to stress degradation as well as the stability of the drug in various environments and also to understand its degradation chemistry. Prediction of in silico toxicity and mutagenicity was aimed at the observed degradation products. Stress degradation along with stability studies and degradation kinetics were performed on mavacamten, and separation of degradation products was carried out by high-performance liquid chromatography. Tandem mass spectrometry studies were executed to characterise the structures of degradation products using product ion fragments. Orthogonally, nuclear magnetic resonance experiments were conducted to elucidate the structures having ambiguity in characterising them. Deductive Estimation of Risk from Existing Knowledge and Structure Activity Relationship Analysis using Hypotheses software were used to establish in silico toxicity and mutagenic profiles of mavacamten and its degradation products. Two degradation products of mavacamten found in acidic hydrolytic stress conditions were separated, identified, characterised, and proposed as 1-isopropylpyrimidine-2,4,6(1H,3H,5H)-trione and 1-phenylethanamine. Mavacamten was found to be stable under different pH and gastrointestinal conditions. The degradation kinetics of mavacamten under 1 N acidic condition followed zero-order kinetics, and it was degraded completely within 6 h. In silico toxicity and mutagenicity studies revealed that 1-phenylethanamine can be a skin sensitiser. A high-performance liquid chromatography method was developed for the separation of degradation products of mavacamten and characterised by liquid chromatography–tandem mass spectrometry and nuclear magnetic resonance. During the manufacturing and storage of drug product, precautions need to be taken when dealing with acidic solutions as the drug is prone to hydrolysis in acidic conditions. The formation of 1-phenylethanamine under these conditions is to be monitored as it is a skin sensitiser.     

Application of coupled liquid chromatography–mass spectrometry in hydrolysis studies of the herbicide ethametsulfuron-methyl

The hydrolysis of the sulfonylurea herbicide ethametsulfuron-methyl [methyl 2-[[[[(4-ethoxy-6-methylamino-1,3,5-triazin-2-yl)amino]carbonyl]amino]sulfonyl]benzoate] was studied in aqueous buffers of different pH values. The reaction was first-order and pH-dependent. Ethametsulfuron-methyl was more persistent in neutral or weakly basic than in acidic solution. Eleven degradation products were detected and tentatively identified by LC/MS/MS analysis. At all pH values studied, the primary pathway of degradation was the cleavage of the sulfonylurea bridge. However, minor degradation pathways have also been observed, such as O-de-ethylation, N-demethylation, and opening of the triazine ring.     

Investigation of the Aquatic Photolytic and Photocatalytic Degradation of Citalopram

This study investigated the direct and indirect photochemical degradation of citalopram (CIT), a selective serotonin reuptake inhibitor (SSRI), under natural and artificial solar radiation. Experiments were conducted in a variety of different operating conditions including Milli-Q (MQ) water and natural waters (lake water and municipal WWT effluent), as well as in the presence of natural water constituents (organic matter, nitrate and bicarbonate). Results showed that indirect photolysis can be an important degradation process in the aquatic environment since citalopram photo-transformation in the natural waters was accelerated in comparison to MQ water both under natural and simulated solar irradiation. In addition, to investigate the decontamination of water from citalopram, TiO₂-mediated photocatalytic degradation was carried out and the attention was given to mineralization and toxicity evaluation together with the identification of by-products. The photocatalytic process gave rise to the formation of transformation products, and 11 of them were identified by HPLC-HRMS, whereas the complete mineralization was almost achieved after 5 h of irradiation. The assessment of toxicity of the treated solutions was performed by Microtox bioassay (Vibrio fischeri) and in silico tests showing that citalopram photo-transformation involved the formation of harmful compounds.     

Application of solid-phase extraction and micellar electrokinetic capillary chromatography to the study of hydrolytic and photolytic degradation of phenoxy acid and phenylurea herbicides

A degradation study of two phenoxy acid [(2,4-dichlorophenoxy) propanoic acid and (2,4,5-trichlorophenoxy) acetic acid] and two phenylurea (diuron and monolinuron) herbicides, spiked at 50 ppb in water, was performed. Some samples were subjected to neutral and basic hydrolysis; other samples were subjected to photolysis using either sunlight or a xenon arc lamp. After degradation, the water samples were preconcentrated using solid-phase extraction (SPE) with Carbopack B columns and analysed by a micellar electrokinetic capillary chromatography (MECC) system with UV detection at 210 nm. Phenoxyacetic acids were not degraded neither by hydrolysis nor by sunlight photolysis, but they were photodegraded when they were exposed to a xenon arc lamp, with half-lives around 300 min. Phenylurea herbicides were hydrolysed at the two-tested pH, with half-lives varying from 25 to 290 days. The main hydrolysis products were the corresponding chloroanilines. Diuron and monolinuron were also degraded when they were exposed to sunlight and xenon arc lamp. The main photodegradation pathway for diuron corresponded to dehalogenation, while for monolinuron dealkylation and hydroxylation were also postulated. The toxicity of the studied herbicides and their degradation products was evaluated by means of Microtox tests. The obtained results indicated that the toxicity of the degraded samples was higher than the toxicity of the herbicides.     

CEC enantioseparations on chiral monolithic columns: a study of the stereoselective degradation of (R/S)-dichlorprop [2-(2,4-dichlorophenoxy)propionic acid] in soil

For the study of the stereoselective degradation of the herbicide 2-aryloxipropionic acid dichlorprop (DCPP) in soil, a porous monolithic chiral column (100 microm id) was prepared by in situ copolymerization of glycidyl methacrylate, methyl methacrylate and ethylene glycol dimethacrylate in the presence of formamide and 1-propanol as the porogen solvents. Subsequently, the epoxide groups at the surface of the monolith were reacted with (+)-1-(4-aminobutyl)-(5R,8S,10R)-terguride as the chiral selector. Optimum conditions for the herbicide resolution by CEC were found using mobile phases consisting of acetic acid/triethylamine mixtures in ACN-methanol (9:1 v/v). Under these conditions fully separation of DCPP enantiomers in the presence of clofibric acid (internal standard) was achieved in about 5 min. Experiments on the incubation of rac-DCPP in soil at room temperature showed the herbicide undergone during 23 incubation days to a degradation to levels 相似文献   

Kinetics and mechanism of the sonolytic conversion of the aqueous perfluorinated surfactants, perfluorooctanoate (PFOA), and perfluorooctane sulfonate (PFOS) into inorganic products

The perfluorinated surfactants perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are recognized as widespread in the environment as well as recalcitrant toward most conventional water treatment technologies. In this study, acoustic cavitation as driven by high-frequency ultrasound is shown to be effective in the degradation of aqueous solutions of PFOS and PFOA and effective over a wide range of concentrations from 10 nM to 10 muM for a given compound. Sulfur, fluorine, and carbon mass balances indicate that mineralization occurs immediately following the degradation of the initial perfluorinated surfactant. Near complete conversion of PFOS and PFOA to CO, CO2, F-, and SO42- occurs due to pyrolytic reactions at the surface and vapor phase of transiently collapsing cavitation bubbles. The initial PFOS or PFOA pyrolytic degradation occurs at the bubble-water interface and involves the loss of the ionic functional group leading to the formation of the corresponding 1H-fluoroalkane or perfluoroolefin. The fluorochemical intermediates undergo a series of pyrolytic reactions in the bubble vapor leading to C1 fluoro-radicals. Secondary vapor-phase bimolecular reactions coupled with concomitant hydrolysis converts the C1 fluoro-radicals to carbon monoxide, carbon dioxide, and HF, forming a proton and fluoride upon dissolution. Sonochemical half-lives, which are calculated from high-temperature gas-phase kinetics, are consistent with kinetic observations and suggest that mineralization occurs shortly after initial perfluorinated surfactant interfacial pyrolysis.     

Abiotic Hydrolysis of Poly[(R)-3-hydroxybutyrate] in Acidic and Alkaline Media

Poly[(R)-3-hydroxybutyrate)], P(3HB), is the most common member of polyhydroxyalkanoates, the natural biopolyesters of intrinsic biodegradability and biocompatibility. Abiotic hydrolysis of P(3HB) was investigated in acid and base media by monitoring the formation of two monomer products, 3-hydroxybutyric acid (3HB) and crotonic acid (CA), from three types of P(3HB) samples, amorphous granules, irregular precipitates and solvent cast films. The soluble monomeric products were not detected in acid solutions (0.1 to 4 N H⁺), but measured as the major hydrolytic products in base solutions (0.1 to 4 N OH⁻). Unlike the protons as catalyst in both hydrolysis and esterification, hydroxyl anions were consumed during formation of carboxylate anions. The amorphous granules of P(3HB) were decomposed 80- to 100-fold faster than the precipitates and solvent cast films. The latter two had around 71% crystallinity. The hydrolysis of amorphous grannules exhibited a quasi 0^th-order reaction rate and the activation energy of saponification was 82.2 kJ/mol, silimar to those of the biotic hydrolysis of P(3HB) by enzymes and living cells.     

Influence of water on the photodegradation of poly(ethylene oxide)

The UV-light degradation of polyethylene oxide (PEO) in aqueous solution was investigated operating under long wavelengths (λ > 300 nm) at 20 °C in different pH conditions varying from 2.3 to 12.0 and at two different concentrations. Thermo-oxidation experiments on PEO aqueous solution at 50 °C are also reported and compared to photo-oxidation results. The formation of oxidation products was followed by infrared analysis of deposits obtained by evaporation of aliquots of irradiated polymer solution. Photo-oxidation led to formates and esters but a third product was also identified, formic acid ions formed by partial hydrolysis of formates. The degradation of PEO in water led to the acidification of the aquatic medium. Size exclusion chromatography (SEC) was used to monitor the changes in molar weight and intrinsic viscosity with irradiation time. It was shown that the photo-oxidation produced a dramatic decrease of the average molar weights which is more important in acidic medium. Total organic carbon (TOC) measurements of the aged aqueous solutions showed that the mineralization of PEO could not be achieved in these photo-oxidative conditions.     

Liquid chromatographic-mass spectrometric studies on the in vitro degradation of a poly(ether ester) block copolymer

A detailed study on the in vitro degradation of a poly(ethylene glycol) and poly(butylene terephthalate) (PEOT/PBT) segmented block copolymer was carried out using liquid chromatography/electrospray-mass spectrometry. Accelerated hydrolysis of PEOT/PBT was achieved by placing the material for 14 days in a refluxing phosphate buffered saline (pH 7.4) solution. All major degradation products and several side-products were identified using both the positive and the negative ion mode. The data indicate that degradation does not only occur in the "soft", but also in the "hard" segments of the polymer. Liquid chromatographic separation is required to distinguish between degradation products with different sequences but identical molecular mass. The addition of ammonium and sodium ions provided important complementary information on the number of monomer units present in the degradation products.     

The degradation of bentazone and chlorotoluron in aqueous solutions by gamma radiation. Biodegradability and toxicity /to Tubifex tubifex/ of radiolysis products

Model aqueous solutions of bentazone and chlorotoluron /herbicide concentration=200 mg.l^–1/ were irradiated with and without simultaneous aeration by -doses in the range 0–52.8 kGy. The degradation of herbicides was studied by UV spectroscopy and chronometric method of herbicide residues determination. The effect of radiation on the biodegradability of bentazone and chlorotoluron solutions were evaluated on the basis of BOD₅/COD ratio determination and toxicity of nondiluted model solutions irradiated by doses in the given range to worms Tubifex tubifex was determined.     

The determination of penicillins by titrations with mercury(II) solution.

A simple technique, involving two titrations with mercury(II) solutions, is described for the determination of penicillins and their degradation products. The first titration, at pH 4–5 on an untreated penicillin solution, gives the amount of degradation products; the second titration, on a hydrolysed solution at the same pH, gives the sum of the degradation products and penicillin degraded during the hydrolysis. Enzymic hydrolysis is superior to alkaline hydrolysis for penicillinase-sensitive penicillins. Enzyme-resistant penicillins should be hydrolysed with alkali at optimum conditions, e.g. for cloxacillin at pH 13.5 for 5 min. A standard deviation of less than 0.5 % was obtained for the penicillins investigated. The method is absolute; calibration with standard penicillin is not necessary.     

An innovative impurity profiling of Avanafil using LC and LC-MS/MS with in-silico toxicity prediction

Degradation of the drug can lead to the formation of toxic substance hence drug quality and stability is a major concern by pharma regulators. A Selected phosphodiesterase type 5 inhibitor drug Avanafil (AV) structure has amide, arylchloro and hydroxide as functional groups which can easily eliminated during hydrolysis. Henceforth, thoroughly chemical stability of AV was carried out according to ICH guideline Q1A (R2). The drug and marketed tablet formulation undergoes degradation in hydrolytic (acid, base, neutral), thermal, photolytic, oxidative conditions and forms a total new sixteen degradation products (D.P.s) which were identified by LC, characterized by LC-MS/MS and probable degradation mechanism for each stress conditions are proposed. All sixteen D.P.s were identified by optimized LC conditions; C18 column using 10 mM ammonium acetate: ACN (60:40, v/v), pH 4.5 as mobile phase at 0.9 mL min⁻¹ of flow rate, 239 nm wavelength at 20 °C column temperature and the method being LC-MS compatible characterized by LC-MS/MS confirmed by relative retention time (RRT). The structure of D.P.s was confirmed from the fragmentation pattern obtained by LC-MS/MS and further probable degradation mechanism for each stress condition is proposed. The drug and its marketed tablet formulation showed similar degradation peaks which were confirmed using RRT, photodiode array (PDA) and LC-MS. Drug degradation happens due to nucleophilic substitution reaction, amide hydrolysis, electron withdrawing properties of amide, dechlorination and bond cleavage due to energy. The amide group in AV structure can undergo hydrolysis, while due to aryl chloride and hydroxide group in structure it undergoes photodecomposition. A comprehensive stress study reveals that AV is more prone to degrade in light, temperature and moisture; hence AV requires proper storage condition temperature below 25 °C with protection to light and moisture. In silico toxicity prediction of physicochemical properties revealed that all the physicochemical parameters of impurities were within the acceptable limit which indicates that no impurity is at any risk of toxicity. In detail, the LC-MS/MS compatible AV degradation study is fully validated as per ICH Q2 (R1) guideline.     

Activation of acyl phosphate monoesters by lanthanide ions: enhanced reactivity of benzoyl methyl phosphate

Acyl phosphate monoesters are intermediates in many biochemical acylation reactions, such as those involving aminoacyl adenylates. Benzoyl methyl phosphate, a typical acyl phosphate monoester, is slowly hydrolyzed in neutral solutions but reacts rapidly with amines. Since biochemical processes of acyl phosphate monoesters involve accelerated reactions with oxygen-centered nucleophiles, we sought catalysts for hydrolysis and methanolysis of benzoyl methyl phosphate to mimic the biochemical outcome. Lanthanide ions are particularly effective catalysts, accelerating reactions much more than comparable levels of magnesium ion. Detailed kinetic analysis of the hydrolysis reactions reveals formation of a 1:1 complex, followed by rapid reaction with a nucleophile. The hydroxide-dependent hydrolysis rate in the europium complex is about 10(5) times that of free substrate with hydroxide. A mechanism that accounts for the data and observed behavior involves bidentate coordination of the metal ion by the acyl phosphate through phosphate and carbonyl oxygens, lowering the energy of the tetrahedral addition intermediate and the associated transition states. The dependence of the metal ion catalyzed process on the concentration of hydroxide ion is consistent with coordinated hydroxide acting as a nucleophile. The reaction of benzoyl methyl phosphate with methanol to form methyl benzoate and methyl phosphate is 30 000 times more rapid in the presence of 0.0001 M lanthanum triflate (in the absence of the metal ion k(obs) = 2.1 x 10(-7) s(-1), at 25 degrees C). Thus, the combination of acyl phosphate esters and lanthanide salts appears to be a promising method for biomimetic acylation of hydroxyl groups.     

应用于水溶液介质中喹啉氧化的电芬顿工艺实验设计方法(英文)

采用碳毡阴极和铂阳极的电芬顿工艺研究了喹啉模型分子8-羟基喹啉硫酸盐（8-HQS）在水溶液介质中的降解行为. 由于电化学诱导芬顿药剂（H2O2,Fe2+）产生大量的羟基活性基（OH）,成为与有机物发生反应直到有机物完全矿化的强有力氧化剂,因此,电芬顿工艺具有很强的氧化能力. 采用正交实验设计确定了水溶液介质中8-HQS降解的操作参数. 结果表明,电流密度和8-HQS的初始浓度是影响降解速度的主要因素. 8-HQS浓度随着电解时间而减少,说明8-HQS的氧化遵循准一级反应动力学. 通过竞争动力学方法确定的由OH引起8-HQS氧化的绝对反应速度常数为1.62×109 mol^-1·L·s^-1. 通过Doehlert 矩阵研究了8-HQS矿化的最佳实验参数,由此确定最佳条件下电芬顿工艺能导致8-HQS在水溶液中的准完全矿化（总有机成分去除率95%）. 对8-HQS水溶液的处理,使得8-HQS矿化前的最终产物为短链羧酸. 同时研究了电芬顿处理中短链羧酸的演变行为. 溶液毒性演变的跟踪研究发现,中间产物的毒性比8-HQS强,但溶液的毒性在中间产物矿化后可以完全消除.     

Characterization of stress degradation products of amodiaquine dihydrochloride by liquid chromatography with high‐resolution mass spectrometry and prediction of their properties by using ADMET Predictor™

The degradation behavior of amodiaquine dihydrochloride, an antimalarial drug, was investigated in solution as well as solid states. The drug was subjected to hydrolytic, photolytic, oxidative, and thermal stress conditions, according to International Conference on Harmonization guideline Q1A(R2). It showed extensive hydrolysis in acidic, alkaline, and neutral solutions both with and without light, while it proved to be stable to thermal and oxidative conditions. In total, six degradation products were formed, which were separated on a C8 column, employing a gradient reversed‐phase high‐performance liquid chromatography method in which acetonitrile and 10 mM ammonium formate (pH 3.0) were used in the mobile phase. To characterize the degradation products, mass fragmentation behavior of the drug was established by direct infusion of solution to quadrupole time‐of‐flight and multiple‐stage mass spectrometry systems. Liquid chromatography with high‐resolution mass spectrometry studies were subsequently carried out on the stressed samples using the same gradient high‐performance liquid chromatography method employed for the separation of the degradation products. Hydrogen/deuterium exchange studies were additionally conducted to determine the number of labile hydrogen atoms. The degradation pathway of the drug was delineated, justified by mechanistic explanation. Lastly, ADMET Predictor™ software was employed to predict relevant physicochemical and toxicity data for the degradation products.