Stereoisomers of alpha-tocopheryl acetate--characterization of the samples by physico-chemical methods and determination of biological activities in the rat resorption-gestation test.
Stereoisomers of alpha-tocopheryl acetate (alpha-TA) have been identified and characterized by means of a recently developed gas-liquid chromatographic technique prior to the determination of their biopotency. It has been shown that totally synthetic all-rac-alpha-TA (dl-alpha-TA) is composed of four pairs of diastereomers (RRS-SSR, RRR-SSS, RSR-SRS, RSS-SRR) in virtually equal proportions. In addition, it has been verified that 2-ambo-alpha-TA (partially synthetic, ex phytol) is an equimolar mixture of RRR-alpha-TA and 2 epi-alpha-TA. Finally, it has been demonstrated that the RRR-alpha-TA (d-alpha-TA) tested was diastereomerically pure. The biopotencies of these alpha-tocopheryl acetate stereoisomers have been evaluated by standardized rat resorption-gestation test. Our first study concerned the comparison of all-rac-alpha-TA with RRR-alpha-TA and resulted in a potency ratio of 1:1.50 or 1:1.48. The first value was derived from the amounts weighed out while the second value was based on the analytically determined alpha-TA content of the stock solutions. Similarly, the comparison of 2-ambo-alpha-TA with RRR-alpha-TA yielded potency ratios of 1:1.32 (amount weighed out) and 1:11.36 (alpha-TA analysed). The influence of the configuration of the side-chain on biopotency has been analysed by a second series of investigations. Comparison of all-rac-alpha-TA with 2-ambo-alpha-TA resulted in a biopotency ratio of 1:1.09 (amount weight out) and 1:1.10 (alpha-TA analysed). However, these slightly higher values for 2-ambo-alpha-TA did not reach statistical significance. These studies demonstrate the validity of the established potency ratio of 1:1.36 for 2-ambo-alpha-TA to RRR-alpha-TA by direct comparison of these compounds. In addition, the experimental ratios for all-rac-alpha-TA to 2-ambo-alpha-TA and for all-rac-alpha-TA to RRR-alph-TA can be grouped into the expression (1:1.10)/(1:1.48) = 1.35. This indirect comparison further supports the accepted value of 1.36 USP Units for 1 mg d-alpha-tocopheryl acetate.
D000818:Animals; D001681:Biological Assay / Q000379:methods; D002849:Chromatography, Gas / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005260:Female; D005327:Fetal Resorption / Q000517:prevention & control; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D024505:Tocopherols; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis; D024502:alpha-Tocopherol / Q000031:analogs & derivatives*
D014810:Vitamin E; D024502:alpha-Tocopherol; D024505:Tocopherols