水中有机磷农药二嗪农的臭氧化降解机制及影响因素

目的臭氧是一种清洁高效的饮用水消毒剂，并能氧化水中有机污染物而不产生消毒副产物，广泛地用于饮用水处理。方法臭氧与有机磷农药二嗪农反应后，采用GC-MS对中间产物进行定性分析，用HPLC监测二嗪农的残留量和中间产物的生成量，研究二嗪农的臭氧降解动力、机制及影响因素。结果二嗪农的臭氧降解由臭氧直接氧化和羟基自由基间接氧化共同作用，并遵循假一级动力学。降解受离子清除剂与溶液pH的影响。加入50mmol／L的离子清除剂和降低溶液pH都使二嗪农的臭氧降解速率常数明显减小。结论通过GC-MS分析，确定了二嗪氧磷为二嗪农的臭氧化中间产物，提高溶液pH有利于二嗪氧磷进一步降解，而加入离子清除剂则不利于二嗪氧磷的降解。     

Alkaline hydrolysis of methyl, ethyl and n-propyl 4-hydroxybenzoate esters in the liquid and frozen states

The alkaline hydrolysis of the methyl, ethyl and n-propyl esters of 4-hydroxybenzoic acid was studied in the liquid and frozen states in sodium hydroxide solutions. The temperature range was −26 to 60°C. Significant acceleration of the reaction rate was evident in the frozen state compared with rates found at liquid state temperatures. The maximum reaction rate in the frozen state occurred in the temperature range −12 to −10°C. Methyl 4-hydroxybenzoate showed more than a 20-fold increased rate constant from 7.17 × 10⁻⁶ s⁻¹ at 30°C to 1.53 × 10⁻⁴ s⁻¹ at −9°C in a 1.00 × 10⁻² M solution of sodium hydroxide. Rate constants in the liquid and frozen states followed pseudo first-order kinetics over 2–4 half-lives of reaction. Data were fitted to a theoretical model describing the reaction rate in the frozen state as dependent upon the increased concentration of solutes in liquid vesicles in the frozen state and the predicted reduction in the reaction rate constant with temperature decrease. Although the data exhibited similar trends to that predicted by the model, there was frequently a 50% difference in the rates observed compared with those predicted. This study has clearly demonstrated that there is a significantly increased rate of hydrolysis of these esters in the frozen state. This is a further indication that it cannot be assumed that drugs stored in solution will necessarily be stabilized, or their stability enhanced, on freezing. Storage under refrigeration conditions (4–8°C) results in enhanced shelf-lives compared with deep-freeze storage at −20°C under the conditions of this study.     

Temperature-responsive and degradable hyaluronic acid/Pluronic composite hydrogels for controlled release of human growth hormone

Temperature-sensitive hyaluronic acid (HA) hydrogels were synthesized by photopolymerization of vinyl group modified HA in combination with acrylate group end-capped poly(ethylene glycol)–poly(propylene glycol)–poly(ethylene glycol) tri-block copolymer (Pluronic F127). The synthesized HA/Pluronic composite hydrogels gradually collapsed with increasing temperature over the range of 5–40 °C, suggesting that the Pluronic component formed self-associating micelles in the hydrogel structure. Upon prolonged incubation in a buffer medium, the micelles slowly degraded due to the hydrolytic scission of the ester linkage between the Pluronic and acrylate group. The mass erosion occurred much faster at 37 °C than at 13 °C, indicating that at the higher temperature, the ester linkage between the Pluronic and acrylate group might be more exposed to an aqueous environment and thus be more readily hydrolyzed due to Pluronic micellization. Incorporation of recombinant human growth hormone in the hydrogel resulted in a sustained release profile which followed a mass erosion pattern.     

盐酸戊乙奎宁在水溶液中的降解机理

Penequine hydrochloride (Ⅰ) is a new potent anticholinergic drug, the degradation mechanism of Ⅰ in aqueous solutions is reported in this paper. Ⅰ is an ethereal compound, stable in neutral and alkaline solutions, but it decomposes in strong acidic solutions. Its main degradation products have been separated and identified by means of TLC, MS, GC/MS and GC/FTIR. With reference to the general degradation rule of ethereal compound and the structure of the degradation products, we deduced that the ether linkage of Ⅰ splits in acidic solutions by the catalysis of hydrogen ion, producing 3- quinuclidinol (DP1) and 1-phenyl- 1-cyclopentyl glycol. The latter turns into 1-phenyl-l-cyclopentyl acetaldehyde through dehydration and rearrangement. In addition, small amounts of other degradation compounds, e. g. benzaldehyde, acetophenone, phenylcyclopentyl ketone, etc. have also been found, but the mechanism remains to be further studied.     

The ICH guidance in practice: stress degradation studies on indinavir sulphate and development of a validated specific stability-indicating HPTLC assay method

A sensitive, selective, precise and stability-indicating high-performance thin layer chromatography (HPTLC) method for analysis of indinavir sulphate both as a bulk drug and in formulations was developed and validated. The method employed TLC aluminium plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of carbon tetrachloride/chloroform/methanol/10% v/v ammonia (4:4.5:1.5:0.05, v/v/v/v). Densitometric analysis of indinavir sulphate was carried out in the absorbance mode at 260 nm. This system was found to give compact spots for indinavir sulphate (Rf value of 0.43 +/- 0.02, for six replicates). Indinavir sulphate was subjected to acid and alkali hydrolysis, oxidation, dry and wet heat treatment, and photo degradation. The drug undergoes degradation under acidic and basic conditions, oxidation, dry and wet heat treatment, and photo degradation. Also the degraded products were well resolved from the pure drug with significantly different Rf values. The method was validated for linearity, precision, robustness, limit of detection (LOD), limit of quantitation (LOQ), specificity and accuracy. Linearity was found to be in the range of 100-6000 ng/spot with significantly high value of correlation coefficient r2 = 0.997 +/- 0.64. The linear regression analysis data for the calibration plots showed good linear relationship with r2 = 0.999 +/- 0.002 in the working concentration range of 1000-6000 ng/spot. The LOD and LOQ were 40 and 120 ng/spot, respectively. Statistical analysis proves that the method is repeatable and specific for the estimation of the said drug. As the method could effectively separate the drug from its degradation products, it can be employed as a stability-indicating one. Moreover, the proposed HPTLC method was utilized to investigate the kinetics of acid degradation process. Arrhenius plot was constructed and activation energy was calculated.     

Determination of cisapride, its oxidation product, propyl and butyl parabens in pharmaceutical dosage form by reversed-phase liquid chromatography

A simple, rapid and reproducible high-performance liquid chromatography (HPLC) assay for cisapride, its oxidation product (OP), propyl and butyl parabens in a pharmaceutical formulation is described. Chromatography was performed at room temperature by pumping acetonitrile–20 mM phosphate buffer pH 7 (50:50, v/v) at 1.5 ml min⁻¹ through C₈ reversed-phase column. Cisapride, OP, propyl and butyl parabens were detected at 276 nm and were eluted at 9.7, 3.1, 5.1 and 7.1 min, respectively. Calibration plots were linear (r>0.999) for all compounds from 0.5 to 200 μg ml⁻¹ for cisapride and OP and 0.1–200 μg ml⁻¹ for propyl and butyl parabens. Detection limits for cisapride, OP, propyl and butyl parabens were 40, 46, 48 and 54 ng ml⁻¹, respectively. Forced degradation investigations showed that cisapride does not undergo degradation under heat, acidic and basic conditions but it was susceptible to oxidation. The proposed method was successfully applied to the assay of cisapride in the presence of preservatives and OP in a commercial suspension.     

Identification of the degradation product of ezlopitant,a non-peptidic substance P antagonist receptor,by hydrogen deuterium exchange,electrospray ionization tandem mass spectrometry (ESI/MS/MS) and nuclear magnetic resonance (NMR) spectroscopy

The degradation product of ezlopitant was isolated from low specific activity material and identified by solution phase hydrogen/deuterium (H/D) exchange and electrospray ionization tandem mass spectrometry (ESI/MS/MS) to be an isopropyl peroxide analog of ezlopitant. The structure of the degradant was further confirmed by nuclear magnetic resonance (NMR) spectroscopy utilizing complete ¹H and ¹³C assignments. Studies were also performed to identify the factors responsible for the oxidative degradation of ezlopitant, which included salt form, storage conditions and salt formation solvent. Of all the variable studies over a 3 weeks period, only a change in the salt form prevented this oxidative degradation.     

Identification and quantitation of sodium-thyroxine and its degradation products by LC using electrochemical and MS detection

High performance liquid chromatography (HPLC) was used in combination with an amperometric and mass spectrometric detection to elucidate and quantitate the degradation products and contaminants of the photo-sensitive Na-thyroxine. Using HPLC with amperometric detection, seven decomposition compounds were separated. These products, which occur mostly as contaminants, were then identified by a developed liquid chromatography-mass spectrometry technique. The same HPLC method was also employed to analyze Na-thyroxine and its degradation products in three commercially available brands of Na-thyroxine tablets.     

Liquid chromatographic analysis of physostigmine salicylate and its degradation products

A simple stability-indicating HPLC assay has been developed for physostigmine salicylate, capable of following its degradation. A 250×5 mm i.d. column packed with 10 μm Bondapak C₁₈ was used, with a mobile phase of acetonitrile–ammonium acetate (pH 6.0; 0.1 M) (50:50, v/v) and flow rate 1.2 ml min⁻¹. All peaks are eluted in <10 min and the method has good precision. The optimum wavelength for detection of degradation products is 305 nm. Application of the assay for a commercial preparation of physostigmine salicylate for injection is presented.     

Nucleotide sequence of the cellulase gene celF of Clostridium thermocellum

The nucleotide sequence of the celF gene of Clostridium thermocellum was determined. The open reading frame extended over 2217 bp. The encoded 739-aa polypeptide, CelF, with a M_w = 82,015, was an endoglucanase with activity against carboxymethylcellulose. The N terminus showed a typical signal peptide, and a cleavage site after Ala-27 was predicted. From residues 28 to 470, the sequence of CelF was related to the catalytic domains of type E₂ endoglucanases, with a strong homology to the endoglucanases CelZ of Clostridium stercorarium and CenB of Cellulomonas fimi. The catalytic region was followed by a 134-aa segment also present in C. stercorarium CelZ and in C. fimi CenB, and belonging to the family of non-catalytic, presumably cellulose-binding domains first identified in Bacillus subtilis endoglucanase. A 21-aa segment rich in Pro/Thr/Ser residues separated the putative cellulose-binding region from the COOH-terminal region, which contained two conserved stretches of 24 amino acids closely similar to those previously described in endoglucanases CelA, CelB, CelD, CelE, CelH and CelX, and xylanase XynZ of C. thermocellum.