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Biomedical subjects

D M Patel

Publications and source records attributed to D M Patel.

31 records · Page 2Linked to original sources

Transient respiratory difficulty following cesarian delivery.

57 newborn infants delivered by planned, repeat cesarian section were studied to determine the role of surfactant in transient neonatal respiratory distress. 22.8% of the newborn infants studied had transient tachypnea of the newborn. The mean amniotic fluid lecithin-sphingomyelin ratio (L/S) was 2.8 in normal infants and 2.6 in infants with transient tachypnea. The mean gastric aspirate L/S at the time of delivery was 3.0 in the normal infants and 2.7 in infants with transient tachypnea. There were no statistically significant differences in either amniotic fluid L/S or gastric aspirate L/S. Based on these results we speculate that, despite altered lung mechanics in neonates with transient tachypnea, lung maturity as determined by L/S ratio does not differ from that of normal neonates.

Amniotic Fluid↗

Novel method of derivatization of an amidinourea (lidamidine) for GLC analysis.

A new quantitative GLC method for analysis of lidamidine hydrochloride (I) was developed. The method was based on derivatization of I to 1-(2,6-dimethylphenyl)-4-methylamino-dihydro-1,3,5-triazin-2-one (II) using dimethylformamide dimethylacetal reagent. Compound II was synthesized and characterized by IR, NMR, mass spectrometry, and elemental analysis. The assigned structure was in agreement with characterization analyses. Cyclization of I to a triazinone using dimethylformamide dimethylacetal reagent presented a new route for the preparation of II.

Chemistry, Pharmaceutical↗

Simultaneous GLC analysis of aspirin and nonaspirin salicylates in pharmaceutical tablet formulations.

The analysis of aspirin and nonaspirin salicylates in buffered and plain tablet formulations employing nearly nonaqueous extraction is described. The results obtained compare favorably with those obtained from USP procedures. A simultaneous assay for aspirin and nonaspirin salicylates in buffered tablets involves the use of an acidified chromatographic siliceous earth column for the separation of the aspirin and nonaspirin salicylates from various buffers or antacids. The methods described here have definite advantages over USP XX procedures, and the buffered aspirin tablet procedures also is adaptable to aspirin formulations containing codeine, acetaminophen, propoxyphene, caffeine, and many antihistamines.

Aluminum Hydroxide↗

Regulation of Neurospora crassa nucleosidases by some environmental factors.

Enzymic cleavage of N-glycosidic bonds of AMP, GMP, and inosine by the cell-free extracts of Neurospora crassa has been studied. The enzymic activities with these substrates appear to be discrete from one another. The levels of these enzymes in the cell vary with age, and are dependent upon the inoculum size, aeration rate, and phosphate level in the medium. Glucose (or ribose) controls the phosphate-mediated repression of all the three nucleosidases of this fungus.

Adenosine Monophosphate↗

Modified USP assay for simultaneous determination of aspirin and nonaspirin salicylates in aspirin and buffered aspirin tablets.

Modified USP procedures are described for the simultaneous determination of nonaspirin salicylates and aspirin in aspirin and buffered aspirin tablets. The existing USP procedures are not stability indicating for intact aspirin when significant levels of nonaspirin salicylates are present, as is often the case in short-term, high temperature stability programs. The modified procedures yeld considerably shorter analysis times and stability-indicating assays for intact aspirin without the need for sophisticated equipment other than that presently required by USP XIX.

Aspirin↗

Solid-state acetylation of codeine phosphate by aspirin.

A nonsolvolytic (solid-state) acetylation of codeine phosphate in the presence of aspirin to yield acetylcodeine phosphate is reported. GLC assays for the simultaneous determination of aspirin and salicylic acid and codeine and acetylcodeine are described. The apparent heat of activation for codeine phosphate is estimated, and the possible reaction mechanisms are discussed.

Acetylation↗

Hydrolytic degradation of 2,6-dichlorobenzylthiopseudourea hydrochloride.

Degradation of 2,6-dichlorobenzylthiopseudourea hydrochloride was followed in basic medium (pH 7.5) to isolate and characterize all possible degradation products. IR, Raman, and NMR spectroscopy, TLC, and elemental analysis were used to identify the products. Degradation of base-hydrolyzed 2,6-dichlorobenzylthiopseudourea hydrochloride produced 2,6-dichlorobenzylthiol and cyanamide and was followed by oxidation (air) to produce bis(2,6-dichlorobenzyl) disulfide, dimerization to give cyanoguanidine, and hydrolysis to yield urea. The kinetics of hydrolysis at 22.5 degrees (pH 7.0 and 7.5) and at 37 degrees (pH 7.0) revealed a pseudo-first-order reaction with respect to the substrate. Apparent first-order rate constants and energy of activation, entropy of activation, and half-life values were determined.

Drug Stability↗

Characterization of impurities in sulfasalazine.

The chemical structures of four impurities isolated from sulfasalazine were determined. Three impurities are the by-products of the reaction process in drug synthesis, i.e., during diazotization of sulfapyridine and during coupling with salicylic acid. Only one contaminant was identified as a starting material, sulfapyridine, in the drug synthesis. The four impurities were characterized as 2-[[p-(2-pyridylsulfamoyl)-phenyl]azo]hydroxybenzene (I), 3-[[P-(2-pyridylsulfamoyl) phenyl]-azo]salicylic acid (II), 5-[[p-[4-(2-pyridylanilino)]-N-phenyl]azo]salicylic acid (III), and sulfapyridine (IV). Compounds I-III are novel molecules, and IV is the precursor of sulfasalazine. The isolation of the impurities was accomplished by TLC and liquid extraction procedures. The methods used to characterize the impurities were a combination of IR, UV, and NMR spectroscopy, mass spectrometry, and TLC. For I and III, comparisons also were made with the synthesized materials to supplement the evaluation.

Chemical Phenomena↗

Kinetics of hydrolysis of fenclorac.

The kinetics of hydrolysis of fenclorac were studied to determine its stability in aqueous solution at different pH's and temperatures. For this study, a stability-specific liquid chromatographic assay method was developed to separate fenclorac from its hydrolysis product, alpha-hydroxy-3-chloro-4-cyclohexylbenzeneacetic acid. The k-pH profile in the 0-12 pH range in various buffer solutions shows that fenclorac is stable in its undissociated form in strongly acidic media and is unstable in neutral and alkaline media. The instability of fenclorac in aqueous solution is proportional to the degree of ionization of the carboxyl group in the 1-4 pH range and is independent of pH above 4. The rate-determining step in the mechanism of hydrolysis of fenclorac involves ionization of the carbon-chlorine bond. The ionization is catalyzed by an intramolecular necleophilic attack on the alpha-carbon by the dissociated carboxyl group, resulting in the formation of an unstable intermediate, a three-membered ring lactone. This unstable intermediate rapidly hydrolyzes to the final hydrolysis product. This mechanism is supported by experimental evidence such as the medium effect, positive salt effect, common ion effect, and substituent effect. Arrhenius parameters for the hydrolysis of fenclorac and its 3-nitro substituted analog were obtained.

Anti-Inflammatory Agents, Non-Steroidal↗

GLC assay for fenclorac.

A rapid stability-indicating GLC method is described for the determination of fenclorac as the diethylamine salt in dosage formulations. The procedure is also applied in detecting and quantitating the weight percent of 3-chloro-4-cyclohexylphenylglycolic acid and alpha-chloro-4-cyclohexylphenylacetic acid impurities associated with the synthesis of the fenclorac drug substance. The former compound, in addition to being an impurity, is also the degradation product of fenclorac. The procedure involves preparations of the silyl derivatives, addition of an internal standard (triphenylethylene), and use of a hydrogen flame-ionization detector. The column, with a phenyl methyl silicone liquid phase and operated at about 195degrees, is well suited for the separation. The silyl derivatives were characterized by GLC-mass spectrometry.

Anti-Inflammatory Agents↗