Stereoisomers of alpha-tocopheryl acetate. IV. USP units and alpha-tocopherol equivalents of all-rac-, 2-ambo- and RRR-alpha-tocopherol evaluated by simultaneous determination of resorption-gestation, myopathy and liver storage capacity in rats.
Whereas the alpha-tocopheryl acetate (alpha-TA) stereoisomers have frequently been compared in various vitamin E tests, only little studies have been made on the free alpha-tocopherols. For this reason, comparative tests of the alpha-tocopherol (alpha-TOH) stereoisomers were made by means of the resorption-gestation method, not only individually but also against the USP standard all-rac-alpha-TA. In some of these tests, the parameter resorption-gestation was supplemented by determination of pyruvate kinase (PK) activity as well as by measurement of the vitamin E level in the liver. Quantitative statistical evaluation of the results was made by weighted probit analysis or by symmetrical parallel line assays. Comparison of all-rac-alpha-TOH (dl-alpha-TOH) with RRR-alpha-TOH (d-alpha-TOH) in the resorption-gestation test revealed an activity ratio of 1:1.38. Compared with 2-ambo-alpha-TOH, RRR-alpha-TOH was more active by a factor of 1.34 (resorption-gestation) or 1.45 (myopathy). On account of its great importance in practice, the comparison between RRR-alpha-TOH and the USP standard was repeated three times. With the parameters resorption-gestation and myopathy, mean activities on a weight basis of 0.69 and 0.74, respectively, were measured. These results fail to confirm the established activity of 1 mg RRR-alpha-TOH = 1.49 USP units. If vitamin E activity is to be given in alpha-tocopherol equivalents (alpha-TE), the values are referred to RRR-alpha-TOH and the calculation is made with their reciprocals. Depending on the parameter used, the activity of 1 mg all-rac-alpha-TA was equivalent to 1.45 alpha-TE (resorption-gestation) or 1.35 alpha-TE (myopathy) and was thus noticeably higher than the established value of 0.67 alpha-TE. For the first time, three parameters were determined simultaneously in the comparison of all-rac-alpha-TOH with the USP standard. Quantitative evaluation yielded the following activities: Resorption-gestation, 0.52; Myopathy, 0.63; liver storage, 0.68. The currently accepted value of 1.10 USP units for 1 mg all-rac-alpha-TOH was thus not even reached approximately. In the light of our experimental findings as well as of those of other laboratories, the activities of the alpha-tocopherol stereoisomers expressed in USP units and of their esters expressed in alpha-tocopherol equivalents need to be corrected.
Weiser
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Vecchi
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Schlachter
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D000818:Animals; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced; D008099:Liver / Q000378:metabolism; D009135:Muscular Diseases / Q000139:chemically induced / Q000201:enzymology; D011247:Pregnancy; D011770:Pyruvate Kinase / Q000097:blood; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000031:analogs & derivatives*
D014810:Vitamin E; D011770:Pyruvate Kinase; D024502:alpha-Tocopherol; D024505:Tocopherols