Influence of Siduron and its Degradation Products on Soil Microflora

Weed Science ◽  
1968 ◽  
Vol 16 (4) ◽  
pp. 417-420 ◽  
Author(s):  
M. L. Fields ◽  
D. D. Hemphill

The herbicide l-(2-methylcyclohexyl)-3-phenylurea (siduron) suppressed the growth of soil bacteria,Azotobacter sp.andChlorella vulgariswhereas siduron had no effect on actinomycetes, filamentous fungi, soil ciliates and other algae. Siduron had no effect upon the growth ofThiobacillus thioparus, Euglena gracilis, andStreptomyces griseus.The degradation product, 2-methylcyclohexylamine (hereinafter referred to as 2-MCHA) suppressed the growth ofAztobacter chroococcumand soil ciliates. Aniline, another degradation product of siduron, depressed the growth ofAspergillus versicolorandA. fischeri;however,A. ochraceus, A. candidus, A. clavatus, A. nidulans, A. flavus, Botrytis cinerea, andRhizopus nigricanswere not affected. None of these fungi was influenced in growth by 2-MCHA.Streptomyces griseusgrew significantly less in the presence of aniline. The growth ofChlamydomonas pyrenoidosa, C. radiata, Anabaena catenula, andRhizobium leguminosarumwere not influenced by 10 ppm aniline or 10 ppm 2-MCHA.

Author(s):  
L. E. Makarova ◽  
A. S. Morits ◽  
N. A. Sokolova

N-phenyl-2-naphthylamine (N-PNA) and phthalates are classified as antibiotic substances. The appearance and accumulation of these substances in the biosphere is associated with their technogenic and biogenic origin (metabolites of plants and bacteria). In this article, we compare the degrading action of such soil bacteria as Rhizobium leguminosarum bv. viceae, Bradyrhizobium japonicum, Pseudomonas syringae pv. pisi, Clavibacter michiganensis sps. Sepedonicus and Azotobacter chroococcum against N-PNA. These bacteria differ in their interaction with pea plants (Pisum sativum L.) synthesising N-PNA. The degradation products were studied using gas chromatography-mass spectrometry in ethyl acetate extracts obtained from culture liquid media, in which N-PNA at a concentration of 10 μM and the bacteria under study were introduced. The decrease in the N-PNA concentration in the extracts obtained using ethyl acetate from culture media, in which N-PNA had been added to a concentration of 100 μM, was monitored following two days of bacterial growth using the methods of high-performance liquid chromatography. It was shown that all the studied bacterial species are capable of degrading N-PNA with the formation of phthalates. The Rhizobium bacteria, endosymbionts of pea plants synthesising N-PNA, and free-living nitrogen-fixing bacteria of the Azotobacter genus showed the highest degrading activity. It was found that N-PNA reduced the viability of all types of bacteria, although to a varying degree. N-PNA had the most negative effect on the viability of the Azotobacter genus, although these bacteria showed a high degrading action against N-PNA. The dependence between the negative effect of NPNA on bacterial viability and the N-PNA concentration was mildly pronounced for Rhizobium and Pseudomonas, although being significant for Bradyrhizobium and Clavibacter.


2019 ◽  
Vol 99 (5) ◽  
pp. 1033-1039
Author(s):  
Madoka Ohji ◽  
Hiroya Harino ◽  
William John Langston

AbstractThe susceptibility of marine bacterial communities to copper pyrithione (CuPT2), zinc pyrithione (ZnPT2) and their degradation product is described and toxicities of these relatively new antifouling biocides compared with those of their harmful organotin (OT) predecessors, tributyltin (TBT) and triphenyltin (TPT). These biocides were added to agar at concentrations of 0, 0.01, 0.1, 1 and 10 mg l−1and coastal seawater including indigenous bacteria added to each batch of agar solution. The number of bacterial colony forming units (CFU) was measured after 7 days culture. Relative CFU (as a percentage of control) was more than 80% at a concentration of 0.01 mg l−1of each compound, except for TBT. Relative CFU decreased as a function of dose of each biocide, although concentration-dependent changes in rate of CFU were relatively low during exposure to degradation products of CuPT2and ZnPT2, pyridineN-oxide (PO) and pyridine-2-sulphonic acid (PSA). Based on comparisons of EC50, TBT was the most bacterio-toxic of the tested compounds (0.2 mg l−1), marginally more so than CuPT2(0.3 mg l−1). Interestingly, EC50values of degradation products of CuPT2and ZnPT2, 2-mercaptopyridineN-oxide (HPT) and 2,2′-dithio-bispyridineN-oxide (PT2) were 0.8 and 0.5 mg l−1, respectively, lower than that of the parent chemical, ZnPT2(1.4 mg l−1). The EC50of PT2was also lower than that of TPT (0.7 mg l−1), implying higher toxicity. Given the overlapping toxicity ranges, these results suggest that marine bacterial communities experience comparably high susceptibility to metal PTs and OTs during their life history.


Author(s):  
SRINIVASU KONDRA ◽  
BAPUJI A. T. ◽  
D. GOWRI SANKAR ◽  
POTTURI MURALI KRISHNAM RAJU

Objective: To propose a comprehensive, simple, and affordable RP-HPLC method for impurity profiling and characterization of unknown degradation products of thiamine hydrochloride injectable formulation. Methods: The chromatographic separation employs gradient mode using the octadecyl silane column using a mobile phase consisting of phosphate buffer with ion pair reagent, acetonitrile, and methanol delivered flow rate at 1.2 ml/min. The detection was carried out at 248 nm using empower software. LC-MS/MS/QTOF hyphenated technique was used for isolation and characterization of unknown degradation impurity. The performance of the method was systematically validated as per ICH Q2 (R1) guidelines. Results: Degradation product observed in accelerated stability was characterized by LC-MS/MS/QTOF hyphenated technique and found m/z value 351.1604 and postulated as an oxidative degradation product of thiamine due to excipient interaction. The validated method was sensitive, selective, and specific data proves the method is precise and accurate from LOQ to 150% level and results are within 95-108% and less than 4.5% RSD. The developed method is linear from 0.03-58.83 µg/ml with a correlation coefficient of more than 0.990 and LOD and LOQ value ranged from 0.03 to1.51 μg/ml. Conclusion: An efficient RP-HPLC method for impurity profiling of thiamine injectable formulation was successfully developed and unknown degradation product observed instability condition samples characterized by LC-MS/MS/QTOF technique. The validated method can be successfully employed for the impurity profiling of thiamine injectable in the quality control department.


1971 ◽  
Vol 54 (4) ◽  
pp. 959-963 ◽  
Author(s):  
R G Nash ◽  
M L Beall

Abstract Two endrin degradation products and a heptachlor degradation product, in addition to heptachlor epoxide, were extracted from soybean plants grown in soil treated with 14C-endrin or 14C-heptachlor. One endrin product was identified as 1,8,9,9,10,11-hexachloropentacyclo[6.3.0.12,5.03′7.06,10]dodecan-12-one (endrin delta ketone); the second endrin product was identified as 1,8,9,9,10,11-hexachlorohexacyclo-[6.3.0.12′5.03,7.06,10.011,12]dodecan-12-ol (endrin alcohol); and the heptachlor product was identified as l,7,8,9,10,10-hexachloro-2,3-6,5-endo-tricyclo[5.2.1.02′6]deca-4,8-diene-exo-3-ol (hydroxychlordene). Identifications were by multiple GLC and TLC techniques.


2019 ◽  
Vol 31 (4) ◽  
pp. 851-854
Author(s):  
Santhosh Guduru ◽  
V.V.S.R.N. Anji Karun Mutha ◽  
B. Vijayabhaskar ◽  
Muralidharan Kaliyaperumal ◽  
Raghu Babu Korupolu ◽  
...  

The stability of aceclofenac under stress conditions was assessed to identify the degradation products. So, it was subjected to stress conditions like acid, base and oxidation, according to ICH guideline Q1A (R2). One degradation product formed when the drug was subjected to acid stress. Three degradation products were formed during the basic stress condition. The drug substance was found to be stable to oxidative stress. The degradants formed during the stress were separated on a C-18 column using gradient preparative HPLC elution. The only product (DP-2) formed during the acid stress and this one is same as of one of the three degradation products (DP-1, DP-2, DP-3) were formed during base stress. 1D and 2D NMR spectra and mass spectral analysis supported the proposed structures for the products. The products DP-2 and DP-3 have been reported earlier but this is the first report of product DP-1 as a degradation product of aceclofenac.


Blood ◽  
1990 ◽  
Vol 76 (7) ◽  
pp. 1341-1348 ◽  
Author(s):  
CM Lawler ◽  
EG Bovill ◽  
DC Stump ◽  
DJ Collen ◽  
KG Mann ◽  
...  

Abstract The validity of markers in plasma of in vitro thrombolysis was investigated in 12 patients with extensive fibrinogen breakdown (greater than 80%, group 1) and in 12 patients with minimal breakdown (less than 20%, group 2). The patients were treated with 100 mg of recombinant tissue-type plasminogen activator (rt-PA) in the “Thrombolysis in Myocardial Infarction II” (TIMI II) trial. Cross- linked fibrin degradation product levels were measured with two variant enzyme-linked immunosorbent assays (ELISAs), both using a fibrin fragment D-dimer specific capture antibody. In one instance, a tag antibody was used that cross-reacts with fibrinogen (pan-specific tag ELISA); in the other, the tag antibody was specific for fibrin fragment D (fibrin-specific tag ELISA). Apparent concentrations of cross-linked fibrin degradation products at baseline were within normal limits with both assays in most patients. At 8 hours after rt-PA infusion, the measured cross-linked fibrin degradation products were increased about twofold to fourfold in group 2 with both assays. However, in group 1, levels were significantly higher with the pan-specific tag ELISA (5.8 +/- 4.2 micrograms/mL) compared with the fibrin-specific tag ELISA (1.5 +/- 1.3 micrograms/mL). This observation was most likely a result of detection of fibrinogen degradation products in the pan-specific ELISA. Apparent levels of fibrinopeptide B beta 1–42, a marker of fragment X formation, increased during thrombolysis from 4.2 +/- 2.8 pmol/mL to 2,000 +/- 230 pmol/mL in group 1 and from 4.1 +/- 2.1 pmol/mL to 300 +/- 43 pmol/mL in group 2, and were correlated significantly with the extent of fibrinogen breakdown (r = -0.8). Fibrinopeptide beta 15–42 levels increased from 4.3 +/- 3 pmol/mL to 70 +/- 19 pmol/mL in group 1, but did not increase in group 2. The apparent increase in group 1 could be explained by cross-reactivity of fibrinopeptide B beta 1–42 in the fibrinopeptide beta 15–42 assay. We conclude that cross-linked fibrin degradation product levels as measured with a pan-specific tag ELISA and fibrinopeptide beta 15–42 levels as measured with certain monoclonal antibody-based ELISA are influenced by the extent of fibrinogen degradation. Fibrinopeptide B beta 1–42 is a marker specific for fibrinogen breakdown. Cross-linked fibrin degradation product levels, measured with a fibrin-specific tag ELISA, appear to be markers specific for thrombolysis. Consequently, assays similar to the fibrin- specific tag ELISA may provide more accurate information when correlated with clinical endpoints.


Pharmaceutics ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 452 ◽  
Author(s):  
Robnik ◽  
Likozar ◽  
Wang ◽  
Stanić Ljubin ◽  
Časar

Drug substance degradation kinetics in solid dosage forms is rarely mechanistically modeled due to several potential micro-environmental and manufacturing related effects that need to be integrated into rate laws. The aim of our work was to construct a model capable of predicting individual degradation product concentrations, taking into account also formulation composition parameters. A comprehensive study was done on active film-coated tablets, manufactured by layering of the drug substance, a primary amine compound saxagliptin, onto inert tablet cores. Formulation variables like polyethylene glycol (PEG) 6000 amount and film-coat polymer composition are incorporated into the model, and are connected to saxagliptin degradation, via formation of reactive impurities. Derived reaction equations are based on mechanisms supported by ab initio calculations of individual reaction activation energies. Alongside temperature, relative humidity, and reactant concentration, the drug substance impurity profile is dependent on micro-environmental pH, altered by formation of acidic PEG degradation products. A consequence of pH lowering, due to formation of formic acid, is lower formation of main saxagliptin degradation product epi-cyclic amidine, a better resistance of formulation to high relative humidity conditions, and satisfactory tablet appearance. Discovered insights enhance the understanding of degradational behavior of similarly composed solid dosage forms on overall drug product quality and may be adopted by pharmaceutical scientists for the design of a stable formulation.


2019 ◽  
Vol 16 (1) ◽  
pp. 55-63
Author(s):  
Rodolfo Ortigara ◽  
Martin Steppe ◽  
Cássia Virginia Garcia

Background: Ambrisentan is a drug used to treat the pulmonary arterial hypertension symptoms, commercialized as coated tablets. Drug quality control is an essential part for the development and release of drugs for consumption; however, there are few studies related to the proposition of analytical methods and stability study for ambrisentan. Objective: The development of an UPLC assay of ambrisentan in tablets with degradation product`s elucidation was proposed. Methods: Tests with different solvents and chromatographic columns were carried out, achieving an optimal condition using mobile phase in gradient mode, Waters® BEH C18 column and detection at 260 nm. Results: Satisfactory system suitability was obtained (theoretical plates, sensitivity and resolution among peaks), with a reduced analysis time (6 minutes). The method was validated in accordance with the international guidelines and it demonstrated adequate specificity, either for the drug assay as for the identification and quantification of degradation product. It showed linearity (r= 0.999), accuracy (degradation products recovery: 98.47 - 102.44; assay recovery: 99.98 - 104.32%) and precision (RSD: 0.69), with limits of quantification and detection in suitable magnitude in order to evaluate possible drug degradation. Conclusion: UPLC method demonstrated to be fast with satisfactory robustness. The main ambrisentan degradation product formed under thermal stress conditions was elucidated by UPLC-MS/MS and its structure was suggested.


Author(s):  
Murlidhar V Zope ◽  
Rahul M Patel ◽  
Ashwinikumari Patel ◽  
Samir G Patel

Objective: The objective was to develop and validate the stability indicating reverse-phase high-performance liquid chromatography method for the quantification of potential degradation products of regadenoson (REGA) from its injectable dosage form.Methods: YMC-PAK ODS AQ, 150 mm × 4.6 mm, 3 μm composed with hydrophobic high carbon loading and a relatively hydrophilic surface chemically bonded to porous silica particles column was used with the temperature maintained at 40°C. Mobile phase A composed of 0.1% triethylamine buffer having pH 4.5 while mobile phase B is 100 % acetonitrile was used for gradient elution with 1.5 ml/min as a flow rate. The wavelength used for quantification was 245 nm and 20 μl as an injection volume. The suitability of the method has been checked and validated according to the International Council for Harmonization (ICH) guidelines for different parameters, namely, specificity, linearity, accuracy, precision, limit of quantification (LOQ), Limit of detection (LOQ), and robustness studies.Results: The resolution between REGA and its two-degradation product is >8.0 for all pairs of components. The high correlation coefficient (r2>0.990) values are for drug and all potential degradation products from LOQ to 150% of specification limits for impurities calculated based on the maximum daily dose of REGA. LOQ for the drug as well as each degradation product is <0.02% w/w. The % relative standard deviation (RSD) for precision and intermediate precision is in the range of 0.17–0.89, and % RSD for precision at LOQ is 0.86–2.35. The % RSD for robustness study is maximum 2.59.Conclusion: The developed method can quantify the specified and unknown degradation products from 0.1% in the injectable dosage form which indicates that method is sensitive. Method fulfills the ICH criteria for its different validation parameters and demonstrates that the developed analytical method is highly specific, precise, and robust and would have a great value when applied in quality control and stability studies for REGA injection.


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