Study on degradation kinetics of epalrestat in aqueous solutions and characterization of its major degradation products under stress degradation conditions by UHPLC-PDA-MS/MS

Drug stability is closely related to drug safety and needs to be considered in the process of drug production,package and storage.To investigate the stability of epalrestat,a carboxylic acid derivative,a reversed-phase high-performance liquid chromatography(RP-HPLC)method was developed in this study and applied to analyzing the degradation kinetics of epalrestat in aqueous solutions in various conditions,such as different pH,temperatures,ionic strengths,oxidation and irradiation.The calibration curve was A=1.6×10^5C–1.3×10^3(r=0.999)with the liner range of 0.5–24μg/mL,the intra-day and inter-day precision was less than 2.0%,as was the repeatibility.The average accuracy for different concentrations was more than 98.5%,indicating that perfect recoveries were achieved.Degradation kinetic parameters such as degradation rate constants(k),activation energy(Ea)and shelf life(t0.9)under different conditions were calculated and discussed.The results indicated that the degradation behavior of epalrestat was pH-dependent and the stability of epalrestat decreased with the rised irradiation and ionic strength;however,it was more stable in neutral and alkaline conditions as well as lower temperatures.The results showed that the degradation kinetics of epalrestat followed first-order reaction kinetics.Furthermore,the degradation products of epalrestat under stress conditions were identified by UHPLC-PDA-MS/MS,with seven degradation products being detected and four of them being tentatively identified.

Degradation kinetics of larotaxel and identification of its degradation products in alkaline condition

Larotaxel, a new taxane compound prepared by partial synthesis from 10-deacetyl baccatin III, is active against tumors. In this research, a selective LC–MS method was developed and validated for the study of degradation kinetics of larotaxel, which was carried out in aqueous solutions with different pH(1.5, 3.0, 5.0, 6.5, 7.4, 9.0, 10 and 11.0) and temperature(0, 25, 37 and 45 °C). The linear range was 0.5–25 μg/mL, the intra-and inter-day precisions were less than 7.0%, and accuracy ranged from 97.4–104.5% for each analyte. The observed rate obtained by measuring the remaining intact larotaxel was shown to follow first-order kinetics. The activation energies for degradation were 126.7 and 87.01 k J/mol at pH 1.5 and 11, respectively. Although larotaxel was stable in pH 5, 6.5 and 7.4 buffers at 37 °C for 24 h during our study, increasing or decreasing the pH of the solutions would decrease its stabilities. Moreover, three main degradation products in alkaline condition were separated by HPLC and identified by Q–TOF–MS. The three degradation products were confirmed as 10-deacetyl larotaxel, 7, 8-cyclopropyl baccatin Ⅲ and 10-deacetyl-7, 8-cyclopropyl baccatin Ⅲ.

Efficient degradation of aqueous dichloromethane by an enhanced microbial electrolysis cell:Degradation kinetics,microbial community and metabolic mechanisms

Dichloromethane(DCM)has been listed as a toxic and harmful water pollutant,and its re moval needs attention.Microbial electrolysis cells(MECs)are viewed as a promising alterna tive for pollutant removal,which can be strengthened from two aspects:microbial inocula tion and acclimation.In this study,the MEC for DCM degradation was inoculated with the ac tive sludge enhanced by Methylobacterium rhodesianum H13(strain H13)and then acclimated in the form of a microbial fuel cell(MFC).Both the introduction of strain H13 and the initi ation in MFC form significantly promoted DCM degradation.The degradation kinetics were fitted by the Haldane model,with V_(max),K_(h),K_(i)and v_(max)values of 103.2 mg/L/hr,97.8 mg/L268.3 mg/L and 44.7 mg/L/hr/cm^(2),respectively.The cyclic voltammogram implies that DCM redox reactions became easier with the setup of MEC,and the electrochemical impedance spectrogram shows that the acclimated and enriched microbes reduced the charge transfe resistance from the electrode to the electrolyte.In the biofilm,the dominant genera shifted from Geobacter to Hyphomicrobium in acclimation stages.Moreover,Methylobacterium played an increasingly important role.DCM metabolism mainly occurred through the hydrolytic glutathione S-transferase pathway,given that the gene dcmA was identified rather than the dhlA and P450/MO.The exogenous electrons facilitated the reduction of GSSG,directly o indirectly accelerating the GSH-catalyzed dehalogenation.This study provides support fo the construction of an efficient and stable MEC for DCM removal in water environment.

Degradation kinetics of functional components of honeysuckle flowers during controlled-atmosphere heat pump drying

To investigate the change law of functional components and exterior color of honeysuckle flowers(HF)during controlled-atmosphere heat pump drying,nitrogen was used as drying medium in this study to reduce the oxygen concentration.The influences of drying temperature,HF’s loading amount and oxygen concentration on chlorogenic acid content,cynaroside content and L value(on behalf of browning degree)were explored,and the degradation kinetics models of chlorogenic acid and cynaroside were constructed.The results showed that chlorogenic acid content,cynaroside content and L value decreased with the rise of temperature,HF’s loading amount and oxygen concentration.The degradation kinetics models of chlorogenic acid and cynaroside during the drying process were established through introducing an exponent r related to time t in the first order reaction kinetics equation.The models had good fitting precision and can be used to predict the degradation law of chlorogenic acid and cynaroside.

Thermal degradation kinetics and lifetime estimation for polycarbonate/polymethylphenylsilsesquioxane composite

The thermal degradation behaviors of poly-carbonate/polymethylphenylsilsesquioxane(FRPC)com-posites were investigated by thermogravimetric analysis(TGA)under isothermal conditions in nitrogen atmo-sphere.The isothermal kinetics equation was used to describe the thermal degradation process.The results showed that activation energy(E),in the case of isothermal degradation,was a quick increasing function of conversion(α)for polycarbonate(PC)but was a strong and decreasing function of conversion for FRPC.Under the isothermal condition,the addition of polymethylphenylsilsesquioxane(PMPSQ)retardanted the thermal degradation and enhanced the thermal stability of PC during the early and middle stages of thermal degradation.It also indicated a possible existence of a difference in nucleation,nuclei growth,and gas diffusion mechanism in the thermal degradation process between PC and FRPC.Meanwhile,the addition of PMPSQ influenced the lifetime of PC,but the composite still met the demand in manufacturing and application.

Degradation kinetic study of lysine in lysine hydrochloride solutions for injection by determining its main degradation product

A limited number of researches have been reported to apply the Arrhenius equation to study the relationship between drugs and its degradation products so far.In the present work,the thermal degradation kinetics of lysine hydrochloride solutions for injection,the special solvent for ademetionine 1,4-butanedisulfonate(SAM)for injection,was investigated at selected temperatures and pH values.The main degradation product of lysine was separated,purified,and confirmed as lysine lactam.A reversed-phase high performance liquid chromatographic(RP-HPLC)method without derivation was developed for the simultaneous determination of lysine and lysine lactam.The results confirmed that both the lysine degradation and lysine lactam generation followed zero-order reaction kinetics.The degradation and generation rate constants increased with increasing temperatures and decreasing pH values.The temperature-dependent degradation and generation reaction could be sufficiently modeled on the Arrhenius equation with the activation energy of 80.14 and 83.22 kJ/mol,respectively.Meanwhile,a linear relationship existed between the amount of lysine degradation and lysine lactam generation since the approximate activation energy.Considering there could be other side effects,we established an upper limit of lysine lactam(500 mg/ml),as the acceptable criteria for stability to estimate the shelf life together with lysine,which made the prediction more accurate and credible.Extrapolation data demonstrated that the lysine hydrochloride solutions for injection could be stable for two years stored at room temperature.

Effect of Graphene Nanoplatelets Presence on the Thermal and Mechanical Properties of Polypropylene Fibers Produced by Melt Spinning

In aiming to obtain fibers with enhanced thermal and mechanical properties,graphene based textile fibers with 144 filaments were developed using an approach in which the PP/GnP(polypropylene/graphene nanoplatelets)nanocomposite was employed as conductive material in a fiber with circular cross-section geometry.The kinetics of thermal degradation was evaluated by the Broido method using thermogravimetric analysis(TGA).Activation energy was enhanced from 260.6 kJ·mol^-1 to 337.4 kJ·mol^-1 compared to the neat PP.GnP increased the thermal stability of the PP,slowing its degradation by thermal depolymerization.Furthermore,the degree of crystallization declined as the GnP content increased,reducing the tenacity of the yarn,but improving its elastic modulus from 91.9 to 95.9 cN/tex,being a promising alternative to produce smart textiles.In conclusion,it has been confirmed that GnP loading up to 1%(w/w)can be incorporated into polypropylene by melt spinning and that the resulting nanocomposite fibers are suitable for several applications in the textile industry.

Kinetics and mechanism of thermal degradation of vegetable-tanned leather fiber

Thermal degradation of vegetable-tanned leather fiber(VLF)was investigated by thermogravimetric analysis aiming to know the exact kinetics and degradation mechanism.The thermogravimetric(TG)and differential thermogravimetric(DTG)curves showed that decomposition of the VLF occurs mainly in the range of 150-600℃,and the latter exhibits asymmetrical peak with a pronounced shoulder.The decomposition process was first analyzed by deconvolution of the experimental DTG curves,followed by reconstruction of the weight loss profiles of two individual processes.Several common isoconversional approaches were applied to calculate the activation energy over a wide range of conversion for the sample,including modified Kissinger-Akahira-Sunose(MKAS),Friedman,and Flynn-Wall-Ozawa.The average activation energy of vegetable-tanned leather fiber was found to be 241.9 kJ mol^(−1) by MKAS method.The activation energy values obtained for the pseudocomponents representing highly-crosslinked and low-crosslinked collagen in VLF were given as 190.6 and 124.8 kJ mol^(−1),respectively.Generalized master plots results suggested that the reaction mechanism for highly-crosslinked collagen follows the random nucleation and growth process at conversion values lower than 0.5.When the conversion is higher than 0.5,the mechanism tends to random scission model.For low-crosslinked collagen,the degradation is mainly governed by random nucleation and nuclei growth.The gaseous products of VLF thermal degradation were analyzed with an online-coupled TG-Fourier transform infrared spectroscopy system.

Treatment Processes of Leachate from a Landfill by Advanced Oxidation Fenton and Ozone-UV

In this paper it is presented the results of advanced oxidation of leachates from a technified sanitary landfill located in the State of Querétaro, Mexico. One characteristic of already stabilized leachates from sanitary landfills like this case, is their difficult degradation, mainly because the organic matter contained is recalcitrant. For the samples collect, four sites were selected, where three points per site were sampled, measuring at each site the parameters: temperature, pH, conductivity, redox potential (ORP) and dissolved oxygen (DO) and leachate samples were collected. On the other hand, the Chemical Oxygen Demand (COD) of crude leachates, leachates acidified and leachates oxidized by Fenton reagent and Ozone-UV combined were analyzed. COD was used to monitor the degradation kinetics. With the results, the ArcGIS software was applied to study the distribution of temperature, dissolved oxygen and COD mainly in the leachate lagoon. For the application of Fenton reagent in the crude leachate oxidation, the pH was first adjusted and Fe2+/H2O2 ratio was optimized. The efficiency of Ozone-UV treatments was studied through COD degradation kinetics. The graphs of in (Ci/Co) vs time, showed that the kinetic processes are of order one, with very acceptable regression coefficients (R2) and extraordinarily similar speed constants (K). With Fenton oxidation, the highest percentage of COD degradation was achieved and with Ozone-UV oxidation, it was possible to practically degrade all the COD.

Assessment by HPLC of the degradation behavior of acitretin under hydrolytic,oxidative,photolytic and thermal stress conditions

Acitretin is a photosensitive oral retinoid with very limited data available on its degradation.The official HPLC method for acitretin determination was insufficient to resolve the degradation products generated during stability studies.Therefore,an isocratic RP-HPLC-UV method was developed for the determination of acitretin in the presence of its related impurities and degradation products.Efficient chromatographic separation was achieved on a Thermo beta-basic column C18(100 mm
4.6 mm,5μm)with mobile phase containing 0.3%(v/v)glacial acetic acid with acetonitrile(ACN)and isopropyl alcohol(IPA)in an isocratic ratio of 70:30 at a flow rate of 1.0 mL/min with the eluent monitored at 360 nm.The method was validated for specificity,linearity,precision,accuracy and robustness.The calibration plot was linear over the concentration range of 50-150μg/mL with a correlation coefficient(r2)of 0.999.The proposed method was used to investigate the degradation kinetics of acitretin under the different degradative conditions.The degradation rate constant(K),half-life(t1/2),and t90 were calculated.Degradation of acitretin followed pseudo-first-order kinetics.The drug was found to be less stable under acidic and photolytic degradation conditions:the photolytic degradation constants for acitretin in sunlight and UV light were 0.002698%and 0.0008402%min1,respectively.The LOD for acitretin and the known impurities were at a level below 0.02%.The method shows consistent recoveries for ACTR(99.8%-101.2%)and also for its known impurities(97.2-101.3%).The method was found to be accurate,precise,linear,specific,sensitive,rugged,robust,and useful for characterizing the stability of this chemical.

Impeded degradation of perovskite solar cells via the dual interfacial modification of siloxane

It is challenging to improve the long-term stability of perovskite solar cells(PSCs) without sacrificing efficiency. The perovskite absorbers degrade from the film surface/interfaces, which follows entangled mechanisms that have not been fully revealed yet.Herein, we decouple and elaborate two distinctive pathways regarding film degradation based on FACsPbI3perovskites.Moreover, a dual interfacial modification strategy has been developed for improving the material’s intrinsic stability, thus leading to the film degrading in a more retardant pathway. The corresponding PSCs achieve a stable power output efficiency of 23.75%.More importantly, the unencapsulated PSCs devices retain over 93% of their initial PCE after the maximum power point(MPP)tracking under the continuous 1-sun illumination and show significantly improved stability after aged under the thermal treatment or stored in ambient atmosphere for over 1500 hours without obvious PCE decay. This work shows the importance of modulating the degradation pathway on stability improvement, and at the same time, proposes a strategy for designing perovskite-based optoelectronics with excellent performance and stability.

Factors influencing the photodegradation of Nnitrosodimethylamine in drinking water

In order to provide basic data for practical application,photodegradation experiment of Nnitrosodimethylamine(NDMA)in aqueous solution was carried out with a low-pressure Hg lamp.Effects of the initial concentration of NDMA,solution pH,dissolved oxygen,and the presence of humic acid on NDMA photodegradation were investigated.NDMA at various initial concentrations selected in this study was almost completely photodegraded by UV irradiation within 20 min,except that at 1.07 mmol/L,NDMA could be photodegraded almost completely in the acidic and neutral solutions,while the removal efficiency decreased remarkably in the alkaline solution.Dissolved oxygen enhanced the NDMA photodegradation,and the presence of humic acid inhibited the degradation of NDMA.Depending on the initial concentration of NDMA,NDMA photodegradation by UV obeyed the pseudo-first-order kinetics.Dimethylamine,nitrite,and nitrate were detected as the photodegradation products of NDMA.^(1)O_(2) was found to be the reactive oxygen species present in the NDMA photodegradation process by UV,based on the inhibiting experiments using tert-butanol and sodium azide.

Pronounced temporal changes in soil microbial community and nitrogen transformation caused by benzalkonium chloride

As one typical cationic disinfectant, quaternary ammonium compounds(QACs) were approved for surface disinfection in the coronavirus disease 2019 pandemic and then unintentionally or intentionally released into the surrounding environment. Concerningly, it is still unclear how the soil microbial community succession happens and the nitrogen(N)cycling processes alter when exposed to QACs. In this study, one common QAC(benzalkonium chloride(BAC) was selected as the target contaminant, and its effects on the temporal changes in soil microbial community structure and nitrogen transformation processes were determined by q PCR and 16S r RNA sequencing-based methods. The results showed that the aerobic microbial degradation of BAC in the two different soils followed first-order kinetics with a half-life(4.92 vs. 17.33 days) highly dependent on the properties of the soil. BAC activated the abundance of N fixation gene(nif H) and nitrification genes(AOA and AOB) in the soil and inhibited that of denitrification gene(nar G). BAC exposure resulted in the decrease of the alpha diversity of soil microbial community and the enrichment of Crenarchaeota and Proteobacteria. This study demonstrates that BAC degradation is accompanied by changes in soil microbial community structure and N transformation capacity.

Degradation behaviors of Nabumetone and its metabolite during UV/monochloramine process:Experimental and theoretical study

This study investigated degradation behaviors of a nonsteroidal anti-inflammatory drug Nabumetone(NMT)and its major metabolite 6-methoxy-2-naphthylacetic acid(MNA)in the coupling process of ultraviolet and monochloramine(UV/NH2Cl).The second-order rate constants of the contaminants reacting with reactive radicals(HO·,Cl·,Cl_(2)·-,and CO_(3)·^(-))were determined by laser flash photolysis experiments.HO·and Cl·contributed predominantly with 52.3%and 21.7%for NMT degradation and 60.8%and 22.3%for MNA degradation.The presence of chlorides retarded the degradation of NMT,while promoted the destruction of MNA,which was ascribed to the photosensitization effects of MNA under UV irradiation.Density functional theory(DFT)calculations revealed that radical adduct formation(RAF)was dominant pathway for both HO·and Cl·reacting with the contaminants,and hydrogen atom transfer(HAT)preferred to occur on side chains of NMT and MNA.NMT reacted with NO_(2)·through single electron transfer(SET)with the second-order rate constant calculated to be 5.35×10^(7)(mol/L)^(-1)sec^(-1),and the contribution of NO_(2)·was predicted to be 13.0%of the total rate constant of NMT in pure water,which indicated that NO_(2)·played a nonnegligible role in the degradation of NMT.The acute toxicity and developmental toxicity of NMT were enhanced after UV/NH_(2)Cl treatment,while those of MNA were alleviated.The transformation products of both NMT and MNA exhibited higher mutagenicity than their parent compounds.This study provides a deep understanding of the mechanism of radical degradation of NMT and MNA in the treatment of UV/NH2Cl.

Treatability studies of naphthalene in soil,water and air with persulfate activated by iron(Ⅱ)

Chemical oxidation was applied to an artificially contaminated soil with naphthalene(NAP).Evaluation of NAP distribution and mass reduction in soil,water and air phases was carried out through mass balance.Evaluation of NAP distribution and mass reduction in soil,water and air phases was carried out through mass balance.The importance of the air phase analysis was emphasized by demonstrating how NAP behaves in a sealed system over a 4 hr reaction period.Design of Experiments method was applied to the following variables:sodium persulfate concentration[SP],ferrous sulfate concentration[FeS04],and pH.The system operated with a prefixed solid to liquid ratio of 1:2.The following conditions resulted in optimum NAP removal[SP]=18.37 g/L,[FeSO4]=4.25 g/L and pH=3.00.At the end of the 4 hr reaction,62%of NAP was degraded.In the soil phase,the chemical oxidation reduced the NAP concentration thus achieving levels which comply with Brazilian and USA environmental legislations.Besides the NAP partitioning view,the monitoring of each phase allowed the variabilities assessment over the process,refining the knowledge of mass reduction.Based on NAP distribution in the system,this study demonstrates the importance of evaluating the presence of semi-volatile and volatile organic compounds in the air phase during remediation,so that there is greater control of the system as to the distribution and presence of the contaminant in the environment.The results highlight the importance of treating the contaminant in all its phases at the contaminated site.

Synchronous mineralization of three aqueous non-steroidal anti-inflammatory drugs in electrochemical advanced oxidation process

Electrochemical degradation performances of three non-steroidal anti-inflammatory drugs(NSAIDs),acetaminophen(ACT),aspirin(ASP)and ibuprofen(IBP),were investigated and compared in their alone and mixture conditions using Ti/SnO_(2)-Sb/La-PbO_(2).The pseudo-first-order degradation kinetics(k)order was k_(IBP-A)(0.110 min^(-1))>k_(ASP-A)(0.092 min^(-1))>k_(ACRT-A)(0.066 min^(-1))in their alone condition,while that was k_(ACT-M)(0.088 min^(-1))>k_(ASP-M)(0.063 min^(-1))>k_(IBP-M)(0.057 min^(-1)) in their mixture condition.The·OH apparent production rate constant of 5.23 mmol L^(-1)min^(-1)m^(-2) and an electrical energy per order(E_(EO)) value of 6.55 Wh/L could ensure the synchronous degradation of the NSAIDs mixture.The mineralization efficiency of NSAIDs mixture was 86.9%at 240 min with a mineralization current efficiency of 1.67%.Acetic acid and oxalic acid were the main products in the mineralization process for the both conditions.In the mixture condition,there were higher k values at lower initial concentrations and higher current density,while the presence of carbonate and humic acid inhibited their degradation.The results indicated electrochemical advanced oxidation process can effectively and synchronously mineralize NSAIDs mixture in wastewater.

Thermal decomposition of poly(ethylene terephthalate)/mesoporous molecular sieve composites

The nonisothermal and isothermal degradation processes of poly(ethylene terephthalate)/mesoporous molecular sieve(PET/MMS)composites synthesized by in-situ polymerization were studied by using thermogravimetric analysis in nitrogen.The nonisothermal degradation of the composite is found to be the first-order reaction.An iso-conversional procedure developed by Ozawa is used to calcu-late the apparent activation energy(E),which is an average value of about 260 kJ/mol with the weight conversion from 0%to 30%,and is higher than that of neat PET.Isothermal degradation results are confirmed with the nonisothermal process,in which PET/MMS showed higher thermal stability than neat PET.The polymer in mesoporous channels has more stability due to the protection of the inorganic pore-wall.These results indicate that mesoporous MMS in PET/MMS composites improve the stability of the polymer.

Fenton oxidation of 2,4- and 2,6-dinitrotoluene and acetone inhibition

The performances and kinetic parameters of Fenton oxidation of 2,4-and 2,6-dinitrotoluene(DNT)in water-acetone mixtures and explosive contaminated soil washing-out solutions were investigated at a laboratory scale.The experimental results show that acetone can be a significant hydroxyl radical scavenger and result in serious inhibition of Fenton oxidation of 2,4-and 2,6-DNT.Although no serious inhibition was found in contaminated soil washing-out solutions,longer reaction time was needed to remove 2,4-and 2,6-DNT completely,mainly due to the competition of hydroxyl radicals.Fenton oxidation of 2,4-and 2,6-DNT fit well with the first-order kinetics and the presence of acetone also reduced DNT’s degradation kinetics.Based on the comparison and matching of retention time and ultraviolet(UV)spectra between high performance liquid chromatography(HPLC)and standards,the following reaction pathway for 2,4-DNT primary degradation was proposed:2,4-DNT→2,4-dinitro-benzaldehyde→2,4-dinitrobenzoic acid→1,3-dinitrobenzene→3-nitrophenol.