scholarly journals Stability of Cephalosporin Prodrug Esters in Human Intestinal Juice: Implications for Oral Bioavailability

1998 ◽  
Vol 42 (10) ◽  
pp. 2602-2606 ◽  
Author(s):  
Klaus Stoeckel ◽  
Werner Hofheinz ◽  
Jean Paul Laneury ◽  
Patrick Duchene ◽  
Steve Shedlofsky ◽  
...  
Keyword(s):  
Enzymatic Hydrolysis ◽  
Degradation Product ◽  
Phosphate Buffer ◽  
Degradation Products ◽  
Cefuroxime Axetil ◽  
Intestinal Fluid ◽  
Intestinal Juice ◽  
Time Courses ◽  
High Degree ◽  
Major Degradation Product

ABSTRACT The levels of degradation of cefetamet pivoxil (CAT), cefuroxime axetil (CAE), and cefpodoxime proxetil (CPD) in 0.6 M phosphate buffer (pH 7.4) and human intestinal juice (pH 7.4) at 37°C over 24 h were compared. Significant differences in the time courses of degradation and in the patterns of degradation products were observed. (i) The relative proportions of the Δ2- and Δ3-cephalosporins were roughly reversed in the two incubation media. In phosphate buffer, the major degradation product was the Δ2-cephalosporin (CAT = 61%; CAE = 74%; CPD = 85%), while in intestinal juice it was the Δ3-cephalosporin (CAT = 86%; CAE = 75%; CPD = 87%). (ii) Generally, the degradation of the prodrug esters progressed faster in intestinal juice than in phosphate buffer (e.g., for CAT the half-lives [t 1/2s] were 0.78 and 4.3 h, respectively). (iii) The two diastereoisomers of CAE and CPD were degraded at different rates in intestinal juice (for the CAE diasteroisomers, t 1/2s = 0.37 and 0.93 h; for the CPD diastereoisomers,t 1/2s = 0.18 and 0.98 h) but were degraded at similar rates in phosphate buffer (for the CAE diastereoisomers, t 1/2 = 1.6 h; for the CPD t 1/2 diastereoisomers, = 2.2 h). It is concluded that (i) the Δ2 isomerization does not significantly affect the bioavailability of prodrug esters since enzymatic hydrolysis in the intestinal fluid proceeds mainly to the active Δ3-cephalosporin and (ii) the high degree of stereoselectivity of the enzymatic ester hydrolysis should make it possible to increase the bioavailabilities of certain prodrug esters (CAE, CPD) by using the more stable diasterioisomer.

scholarly journals Toxicity of Canola-Derived Glucosinolate Degradation Products in Pigs—A Review

Animals ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 2337
Author(s):  
Jung Wook Lee ◽  
In Ho Kim ◽  
Tofuko Awori Woyengo
Keyword(s):  
Degradation Product ◽  
Degradation Products ◽  
Acidic Ph ◽  
Neutral Ph ◽  
Aliphatic Glucosinolates ◽  
Epithiospecifier Protein ◽  
Swine Diets ◽  
Major Degradation Product

Canola co-products are widely included in swine diets as sources of proteins. However, inclusion of canola co-products in diets for pigs is limited by toxicity of glucosinolate degradation products. Aliphatic and aromatic glucosinolates are two major classes of glucosinolates. Glucosinolate degradation products derived from aliphatic glucosinolates (progoitrin) include crambene, epithionitriles, and goitrin, whereas indole-3-acetonitrile, thiocyanate, and indole-3-carbinol are the major aromatic glucosinolates (glucobrassicin)-derived degradation products. At acidic pH (<5.7), progoitrin is degraded by myrosinases to crambene and epithionitriles in the presence of iron, regardless of the presence of epithiospecifier protein (ESP), whereas progoitrin is degraded by myrosinases to goitrin in the absence of ESP, regardless of the presence of iron at neutral pH (6.5). Indole-3-acetonitrile is the major degradation product derived from glucobrassicin in the absence of ESP, regardless of the presence of iron at acidic pH (<4.0), whereas thiocyanate and indole-3-carbinol are the major glucobrassicin-derived degradation products in the absence of ESP, regardless of the presence of iron at neutral pH (7.0). In conclusion, the composition of glucosinolate degradation products is affected by parent glucosinolate composition and hindgut pH. Thus, toxicity of canola co-product-derived glucosinolates can be potentially alleviated by modifying the hindgut pH of pigs.

scholarly journals Differences in susceptibility of marine bacterial communities to metal pyrithiones, their degradation compounds and organotin antifouling biocides

2019 ◽  
Vol 99 (5) ◽  
pp. 1033-1039
Author(s):  
Madoka Ohji ◽  
Hiroya Harino ◽  
William John Langston
Keyword(s):  
Life History ◽  
Degradation Product ◽  
Bacterial Communities ◽  
Degradation Products ◽  
High Susceptibility ◽  
Zinc Pyrithione ◽  
Bacterial Colony ◽  
Indigenous Bacteria ◽  
Antifouling Biocides ◽  
Colony Forming Units

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.

Glyphosate Residues in Soil and Air: An Integrated Review

2020 ◽  
Author(s):  
Evagelia Tzanetou ◽  
Helen Karasali
Keyword(s):  
Degradation Product ◽  
Critical Review ◽  
Safety Evaluation ◽  
Environmental Safety ◽  
Soil Ecosystem ◽  
Aminomethylphosphonic Acid ◽  
The Relationship ◽  
Surface And Groundwater ◽  
Major Degradation Product

Glyphosate [N-(phosphonomethyl) glycine] (GPS) is currently the most commonly applied herbicide worldwide. Given the widespread use of glyphosate, the investigation of the relationship between glyphosate and soil ecosystem is critical and has great significance for its valid application and environmental safety evaluation. However, although the occurrence of glyphosate residues in surface and groundwater is rather well documented, only few information are available for soils and even fewer for air. Due to this, the importance of developing methods that are effective and fast to determine and quantify glyphosate and its major degradation product, aminomethylphosphonic acid (AMPA), is emphasized. Based on its structure, the determination of this pesticide using a simple analytical method remains a challenge, a fact known as the “glyphosate paradox.” In this chapter a critical review of the existing literature and data comparison studies regarding the occurrence and the development of analytical methods for the determination of pesticide glyphosate in soil and air is performed.

IMPURITY PROFILING IMPURITY PROFILING OF THIAMINE HYDROCHLORIDE INJECTION BY RP-HPLC AND CHARACTERIZATION OF DEGRADATION PRODUCT BY LC-MS/MS/QTOF

2020 ◽  
pp. 151-161
Author(s):  
SRINIVASU KONDRA ◽  
BAPUJI A. T. ◽  
D. GOWRI SANKAR ◽  
POTTURI MURALI KRISHNAM RAJU
Keyword(s):  
Degradation Product ◽  
Degradation Products ◽  
Hplc Method ◽  
Thiamine Hydrochloride ◽  
Injectable Formulation ◽  
Hyphenated Technique ◽  
Isolation And Characterization ◽  
Impurity Profiling ◽  
Rp Hplc

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.

Extraction and Identification of Endrin and Heptachlor Degradation Products

1971 ◽  
Vol 54 (4) ◽  
pp. 959-963 ◽  
Author(s):  
R G Nash ◽  
M L Beall
Keyword(s):  
Degradation Product ◽  
Degradation Products ◽  
Heptachlor Epoxide ◽  
Soybean Plants

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.

scholarly journals Isolation and Structural Characterization of Degradation Products of Aceclofenac by HPLC, HRMS and 2D NMR

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 ◽  
...  
Keyword(s):  
Degradation Product ◽  
Degradation Products ◽  
Acid Stress ◽  
2D Nmr ◽  
Stress Conditions ◽  
Preparative Hplc ◽  
Mass Spectral ◽  
2D Nmr Spectra ◽  
The Stability

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.

Furosemide Concentrations in Serum and Urine, and Its Binding by Serum Proteins as Measured Fluorometrically

1974 ◽  
Vol 20 (2) ◽  
pp. 152-158 ◽  
Author(s):  
A W Forrey ◽  
B Kimpel ◽  
A D Blair ◽  
R E Cutler
Keyword(s):  
Quantum Yield ◽  
Diethyl Ether ◽  
Degradation Product ◽  
Phosphate Buffer ◽  
Serum Proteins ◽  
Extraction Ratio ◽  
Fluorometric Method ◽  
Internal Standards ◽  
Serum And Urine

Abstract We describe a modification of the fluorometric method of Häussler and Hajdú [Arzneim. Forsch. 14, 704 and 709 (1964)] for assay of furosemide in either serum or urine. A 1-ml sample, acidified to pH 2, is extracted with 5 ml of diethyl ether; 4 ml of the ether is back-extracted into 1 ml of phosphate buffer (pH 7.0, 0.1 mol/liter), and finally acidified with 1 ml of dilute HCl (0.6 mol/liter). A procedure for estimating blanks in urine was derived to correct for dilution caused by diuresis. Internal standards are used, and the "effective" extraction ratio is used to correct for the effects of quenching and extraction differences. In equilibrium, 93% of the drug is bound to serum proteins; 65% is tightly bound. Erythrocytes contain less than 5% of the drug. Quantum yield of fluorescence at pH 1 is 0.0496 for furosemide and is 0.0163 for 4-chloro-5-sulfamoylanthranilic acid. Furosemide fluorescence diminishes with increasing pH, while that of 4-chloro-5-sulfamoylanthranilic acid (a degradation product) increases.

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