Stability of Pharmaceuticals

The pharmacokinetic characteristics of testosterone propionate were studied in normal men after a single im dose of 25 mg testosterone propionate-19,19,19-d3. Plasma levels of testosterone propionate-19,19,19-d3, its active metabolite testosterone-19,19,19-d3, and endogenous testosterone were measured by gas chromatography-mass spectrometry. Testosterone propionate-19,19,19-d3 was gradually transferred from the im injection site to the systemic circulation. The plasma levels of testosterone propionate-19,19,19-d3 were maintained at 2-4 ng/ml between 3 and 36 h after administration. Plasma testosterone-19,19,19-d3 levels were maintained above the physiological testosterone level for 48 h, while plasma levels of endogenous testosterone changed little.

Pharmacokinetic properties of testosterone propionate in normal men

A review is given on methods of practical importance for the determination of steroids in pharmaceutical formulations (sex hormones, adrenocortical steroids, vitamins D, cardiac glycosides). Spectrophotometric, fluorimetric, chromatographic (TLC, GC, HPLC) and polarographic methods are discussed, others are briefly mentioned. Methods of fundamental importance in biological-clinical analysis but not in pharmacy have been omitted.

Determination of steroids in pharmaceutical formulations

https://lib.dr.iastate.edu/cgi/viewcontent.cgi?article=5801&context=rtd

Isolation and partial characterization of

A mild method for the isolation of flavins from plant tissues was developed and applied. The method consists of an aqueous extraction in the presence of enough ammonium sulfate to form a saturated solution, and isolation using 1) columns of a resorcinolformaldehyde resin, 2) columns of unwashed talc, and 3) thin-layer chromatograms of Silica Gel H. Amounts of riboflavin as small as 1.5 ng. obtained from 1/40 of one corn coleoptile were detectable. Using this method, a compound which was characterized as lumichrome was detected when etiolated seedlings of corn and of oats, and cells of yeasts were exposed to six hours of sunlight or to 1100 foot-candles of artificial light for the same period of time. Compounds which are probably natural derivatives of riboflavin were found in etiolated seedlings of oats and Job's tears. The work with oats confirmed an earlier report of a new fla'^'-n and showed this flavin to be negatively charged, and apparently substituted on neither the ring nor the second or third carbon of the side chain. The two compounds from Job's tears were not charged, and apparently not substituted on the ring, the second, or third carbon of the side chain. These compounds did not correspond chromatographically to any derivatives of riboflavin whose structure is now known.

Isolation and partial characterization of flavins from plants

Multi-stage extraction from a solution of testosterone oily injection in heptane with 85% ethanol yields a hormone extract in which testosterone can be specifically determined by applying the sulphuric acid-picric acid reaction. A parallel analysis of standard samples, which are dissolved in different oily media, and of identical blank media shows that the oily residues and pharmaceutical adjuvants do not interfere at a wavelength of 640 nm and that the recoveries, calculated by comparison with a standard or directly from the value of E1%1cm for the ester concerned, are within the range 98.4–101.6%. The precision, for assays of 25 mg ml–1 solutions, is ±1%.Testosterone is also determined with similarly high accuracy in complex injections containing oestradiol or progesterone although these hormones pass quantitatively into the hormone extract.The possibility of determining both testosterone and either progesterone or oestradiol in the same extract, without further manipulation, constitutes a useful saving in time and labour.

Specific determination of testosterone in oily injections

A method for separating riboflavine from vitamin mixtures is described. The acidified aqueous solution is passed through a small column of large particle size talc on which the riboflavine is selectively and quantitatively adsorbed. Successive washings with 0–01 n hydrochloric acid and 5–10% dioxan remove the other components almost completely. The vitamin, eluted with 20% dioxan, is measured spectrophotometrically.

Quantitative separation of riboflavine from vitamin mixtures.

The chromogen resulting from preliminary treatment of testosterone with concentrated sulphuric acid gives a stable green colour on further treatment with a saturated aqueous solution of picric acid. The absorbance graph of the green colour shows two maxima, at 470 and 640 nm, and obeys Beer's law. Under the specified conditions, absorbances at the two maxima have a fairly constant ratio (2·80 to 2·96), which is characteristic for testosterone and its esters in amounts ranging from 125 to 250 µg. Spectral and structural studies involving a large number of steroids show that the colour reaction is specific for testosterone.

Emil Fahmy

Papers

Specific determination of testosterone in oily injections

Quantitative separation of riboflavine from vitamin mixtures.

Studies on a specific colour reaction for the determination of testosterone