Statistical optimisation applied to the spectrophotometric study of the tolmetin-Fe(III) complex.
Tolmetin sodium has been examined and determined from dosage forms as its Fe(III) complex and the method has been optimized by statistical optimization.
Micro-determination of tolmetin in plasma by electron-capture gas chromatography.
A highly sensitive, specific and precise gas chromatographic method for the determination of the anti-inflammatory agent tolmetin in micro-samples of blood plasma is described. The pentafluorobenzyl ester derivative of tolmetin, which can be detected down to picogram levels using electron-capture detection, has been prepared. The lowest concentration of tolmetin which can be measured accurately and precisely (coefficient of variation less than 15%) in a 25-microliter plasma sample is 0.1 microgram/ml. Previously reported assays require a sample size 20--80 times larger and have a detection limit of 0.5 microgram/ml. The pentafluorobenzyl ester derivatives of both tolmetin and the internal standard have been identified from their chemical ionization mass spectra. The present method was found to be in good agreement with another published gas chromatographic assay when both methods were employed to analyze the same set of plasma samples from four juvenile reheumatoid arthritic patients.
BIOSYNTHESIS OF DAUNORUBICIN GLYCOSIDES: ANALYSIS WITH BLOCKED MUTANTS
ABSTRACT Daunorubicin (daunomycin; NSC 82151) is an anthracycline antibiotic that is useful in the treatment of human leukemias. Several Streptomyces species accumulate higher glycosides of daunorubicin, which can be converted to daunorubicin by simple hydrolysis. We isolated a number of mutants of a daunorubicin glycoside-producing streptomycete, and found that some were deficient in accumulation of daunorubicin glycosides. One such mutant accumulated no detectable anthracyclines, while other mutants accumulated anthracyclines or aglycones that have not been reported before or have been described as co-metabolites of daunorubicin glycosides. Some of these anthracyclines and aglycones were purified and used as substrates in bioconversion experiments with various mutants. The results allowed us to construct a proposed pathway for the biosynthesis of daunorubicin glycosides by this streptomycete. KEYWORDS Anthracycline; daunorubicin; biosynthesis; blocked mutants; biotransformation.