Biomedical subjects

B S Rutherford

Publications and source records attributed to B S Rutherford.

5 recordsLinked to original sources

PubMed1992

Effect of impurities on estradiol crystallization in a sustained-release implant.

During the development of a silicone rubber implant for the delivery of estradiol 17-beta some batches of implants made from a certain lot of commercial estradiol inexplicably developed surface crystals of estradiol after several days of storage. An impurity profile was obtained for 28 lots of estradiol by a newly developed HPLC method. One or more impurities may have had a role in the spontaneous crystal growth on the surface of the implants, because the one lot of estradiol that initially had surface crystals on aging produced acceptable implants after multiple recrystallizations. Attempts to isolate suspected impurities for characterization were unsuccessful. During the manufacture of the implants, temperatures sufficient to melt the estradiol (mp, 173-179 degrees C) were used. It was expected that, upon implant cooling, melted impure estradiol would form a thermodynamically more active (i.e., noncrystalline) physical form. This metastable form could have migrated to the implant surface, where ambient conditions favored crystallization. Because melted estradiol of a higher purity tended to crystallize more readily, it was less likely to form a glass upon cooling. The phenomenon of surface crystallization was limited to one lot of estradiol with the highest level of impurities. Data from differential scanning calorimetry studies supported this conclusion.

Calorimetry, Differential Scanning↗

PubMed1987

General method validation guidelines for pharmaceutical samples.

Method validation guidelines, which provide an organizational structure for the design and evaluation of a validation procedure, are presented for a wide range of pharmaceutical applications. The validation guidelines are based on the analyte concentration/sample matrix combination to which the method will be applied. These guidelines include the selection of appropriate validation parameters, design considerations for evaluation, and a discussion of acceptance guidelines for the determination of acceptable method performance. A set of tables is included which illustrates the selection and testing procedure and tailors the entire validation process to the specific characteristics of the determination to be made.

Chemistry, Pharmaceutical↗

PubMed1976

GLC determination of aprindine: quantitation and stability measurement.

A GLC method of analysis of a new antiarrhythmic agent, aprindine, is described. The raw material of the new drug substance, supplied as the hydrochloride salt, is dissolved in deionized water, and the base is liberated by a 10% aqueous solution of sodium carbonate. aprindine is extracted with chloroform and mixed with the internal standard, 5alpha-cholestane. GLC is perfomed on a glass column packed with 3.8% W-98 on Chromosorb W-HP. Quantitation is achieved by computer calculation of the peak area ratios. GLC-mass spectral analysis indicates that the observed peak is that of aprindine, with a molecular ion at m/e 322. The retention times of aprindine and the internal standard are 2.0 and 5.8 min, respectively. All synthetic precursors show a shorter retention time than aprindine. This GLC method is applied to the quantitative determination of aprindine as raw material and in capsule and ampul formulations. The method is also used to measure the stability of aprindine to acid, base, dry, heat, refluxing, and UV light and to pH variations.

Aprindine↗

PubMed1975

GLC determination of 17 alpha-ethynylestriol 3-cyclopentyl ether.

A rapid, sensitive, and accurate GLC method of analysis of a new estrogenic drug, 17 alpha-ethynylestriol 3-cyclopentyl ether, was developed. The drug and the internal standard, tetratriacontane, are dissolved in chloroform, and an aliquot is heated with N-trimethylsilylimidazole at 80 degrees for 30 min. The silylated sample is chromatographed using a column packed with 1% methyl vinyl silicone gum on Gas Chrom Q. Quantitation is achieved by computer calculation of the peak area ratios. The observed peak is the 16alpha,17beta-bistrimethylsilyl derivative of the new drug substance. The GLC method was applied to the quantitative determination of the estrogenic compound in a tablet formulation containing 25 mug/tablet.

Chromatography, Gas↗

PubMed1975

3-Substituted 2',3'-dihydroestra-1,3,5(10)-trieno (16alpha, 17alpha-b)furan-17beta-ols as potential estrogens.

The preparation, characterization, and estrogenic activity of the two new steroids 3-(cylopentyloxy)-2',3'-dihydroestra-1,3,5(10)-trieno(16alpha,17alpha-b)furan-17beta-ol and 2',3'-dihydroestra-1,3,5(10)-trieno(16alpha,17alphs-b)furan-3,17beta-diol are described. The compounds were found to be 0.1 and 0.002 respectively, as potnet as estrone in a test design to measure the uterine weight gain of treated immature mice relative to controls.

Animals↗