Origin of monacolin L from Aspergillus terreus cultures.

In freshly harvested Aspergillus terreus cultures grown for the production of lovastatin (formerly called mevinolin), no monacolin L could be detected. However, during the isolation of lovastatin, significant quantities of monacolin L appeared. It has been discovered that a new metabolite structurally related to the members of the monacolin series is present. This metabolite is unstable and under mildly acidic conditions and elevated temperature, it converts to monacolin L. The subject metabolite is proven to be a hydroxylated derivative of dihydromonacolin L identified as 3 alpha-hydroxy-3,5-dihydromonacolin L. It seems that all monacolin L found later during various treatments of the broth and broth extracts is formed from that precursor via a dehydration reaction. The new metabolite was converted to its phenacyl ester, by means of extractive alkylation, for isolation and structure elucidation by chemical, chromatographic and spectroscopic methods. This ester, on standing, gradually formed the corresponding lactone.

Quantitative thin-layer chromatography in accelerated stability studies for prediction of inherent sensitivity of drugs toward oxygen.

This paper discusses a novel technique for studying the inherent sensitivity of materials toward oxygen and the utility of quantitative thin-layer chromatography, as a tool in such studies. The degradation generally followed first order kinetics up to about 60% decomposition, indicating that the usual kinetic treatment applied to homogeneous systems can be used. The method can also detect degradation products, in many cases adding a considerable diagnostic element to its predictive value. Among the model compounds tested testosterone was the most stable with ca. 95% recovery following a 190-h exposure to air on standard silica gel plates. The half-life time of the other model substances under similar experimental conditions was estimated by means of direct measurements or by extrapolation, and found to range from approximately 300 h to 1 h 10 min with cortisone marking the upper value and cholesta-3,5-diene the lower one.

Quantitative analysis of cephamycin C in fermentation broths by means of thin-layer spectrodensitometry.

A method has been developed that consists of one-dimensional thin-layer chromatography of the samples on pre-coated silica gel 60F254 plates followed by an in situ spectrophotometric evaluation of the chromatograms at 273 nm. Statistical evaluations showed a linear calibration (r2 greater than 0.999) for the range of 0.2-20 microgram/spot. The relative standard deviations for broth samples containing 1.505 and 12.47 microgram Cephamycin C per spot were 3.61 and 1.07%, respectively. The recovery was virtually quantitative: 97.6%. The correlation with a liquid chromatographic method was quite acceptable with r2 = 0.99124 and b = 0.998 (slope).

Plasma concentrations and urinary excretion of the antiarrhythmic quaternary ammonium compound QX-572 in man.

A quantitative thin layer chromatographic (TLC) method has been developed for determination of the antiarrhythmic quaternary ammonium compound N,N-bis (phenylcarbamoyl methyl) dimethylammonium chloride (QX-572) in biological materials. Prior to chromatography QX-572 was transferred into chloroform as perchlorate by ion pair extraction. Tritium-labelled QX-572 was used as the internal standard and a TLC scanning spectrophotometer equipped with a linear detector system afforded the required accuracy, specificity and simplicity. The method was used to determine QX-572 in plasma from 11 patients with various cardiac diseases who received QX-572 8 mg/kg body wt. as an intravenous infusion over 30 min. There was a rapid initial decay of the plasma levels from 11.0+/-1.1 mug/ml (mean+/-SE) at the end of infusion to 3.5+/-0.5 mug/ml after 30 min. 240 min after commencement of the infusion the plasma level was 0.7+/-0.1 mug/ml. In these patients 22+/-2% (mean+/-SE) of the total administered dose of QX-572 was excreted unchanged in urine during the 24 hours following infusion of the drug. A second group of 28 patients with acute myocardial infarction also received QX-572 8 mg/kg body wt. Their plasma levels did not differ significantly from those found in the first group of patients. There was a poor correlation between the amount of QX-572 administered and plasma level at the end of the infusion. The study has provided some preliminary data about the pharmacokinetics of QX-572, but before a detailed analysis can be done data from longer periods of observation is required. The present results suggest that in future QX-572 can be administered in a standardized dosage, what would be advantageous in practice.