BIODISCRIMINATION OF THE 8 ALPHA-TOCOPHEROL STEREOISOMERS RESULTS IN PREFERENTIAL ACCUMULATION OF THE 4 2R FORMS IN TISSUES AND PLASMA OF RATS

According to the USP, 2R,4'R,8'R-alpha-tocopheryl acetate (RRR-alpha-T Ac) is 1.36 times more active than all-rac-alpha-tocopheryl acetate (a ll-rac-alpha-TAc). The all-rac form contains 12.5% each of the stereoi somers RRR, RRS, RSR, RSS, SSS, SSR, SRS and SRR, which display differ ent biopotencies. In the present study, female rats fed a vitamin E-de ficient diet were administered 0.82 mg of ali-rac-alpha-TAc or 0.60 mg of RRR-alpha-TAc daily for up to 90 d. alpha-Tocopherol concentration s in liver, brain, adipose tissue and plasma were not significantly di fferent among groups on treatment d 64 and 90. Thus, equipotent dosage s of all-rac-alpha-TAc or RRR-alpha-TAc resulted in equimolar alpha-to copherol plasma and tissue concentrations. A comparison with rats admi nistered tocopherol-free placebo showed that plasma and tissue cu-toco pherol of alpha-TAc-treated rats represented alpha-tocopherol uptake d uring the repletion period. The eight individual alpha-tocopherol ster eoisomers in tissues and plasma were determined by chiral HPLC and cap illary gas chromatography. Rats treated with all-rac-alpha-TAc prefere ntially accumulated the four 2R alpha-tocopherol stereoisomers (15-22% each, sum of all 2R = 70-86%) in tissues and plasma. The remaining 14 -30% were 25 stereoisomers with a predominance of the SRS form, In con clusion, all-rac-alpha-TAc administration led to the presence of all e ight alpha-tocopherol stereoisomers in rat liver, brain, adipose tissu e and plasma. The four 2R stereoisomers including RRR-alpha-tocopherol were equally and significantly enriched. This confirmed that the conf iguration at C-2 of the alpha-tocopherol molecule has a major impact o n stereoisomer biodiscrimination. Furthermore, the results are in agre ement with the hypothesis that for alpha-tocopherol stereoisomers, bio potency differences are related to corresponding differences of alpha- tocopherol concentrations.