500 THE TOCOPHEROLS 



succinates, fatty acid esters, nitrobenzoates, and phosphates of a-tocoph- 

 erol are described^''"'*'' but have remained laboratory products. 



D. PRODUCTION CONTROL TESTS 



Considerable experience with various physical and chemical techniques 

 permits the generalization that the Emmerie-Engel reaction^^ is the method 

 of choice for production control in which total tocopherol values suffice. ^^'^'^ 

 However, procedures employing eerie sulfate titration of tocopherols, modi- 

 fications of Kofier's method,^^ serve a useful purpose in control analyses on 

 pure tocopherols. The quantity of a-tocopherol in the preparation, how- 

 ever, is the important question and is obtained by determining the non-a- 

 tocopherol moiety by the nitroso method and subtracting this from the 

 amount of total tocopherols determined separately.*^ Direct determination 

 of cc-tocopherol, after removal of non-a-tocopherols by careful, arbitrary 

 washing with sulfuric acid, is used by a regulatory agency in inspection 

 control assays.'*'^ 



Products containing tocopherol esters must be carefully saponified be- 

 fore analyzing for total and individual tocopherols. Quantitative hydrolysis 

 is possible if proper precautions to prevent tocopherol loss and destruction 

 are observed. For example, exclusion of air during reaction and neutraliza- 

 tion and use of an antioxidant are necessary .*^"^- 



Bioassays of final products and praticularly of new types of preparations 

 are desirable, since the chemical methods do not distinguish the various 

 unnatural isomers of a-tocopherol from the natural d isomer. The physio- 



" F. Hoffmann-La Roche & Co., Swiss Pat. 208,851 (May 16, 1940). 



35 F. Hoffmann-La Roche & Co., German Fat. 711,243 (Aug. 28, 1941). 



36 F. Hoffmann-La Roche & Co., German Pat. 712,743 (Oct. 2, 1941). 

 "F. Hoffmann-La Roche & Co., Swiss Pat. 216,825 (Sept. 15, 1941). 

 38 P. Karrer, U.S. Pat. 2,231,125 (Feb. 11, 1941). 



^^ L. I. Smith, W. B. Renfrow, Jr., and J. W. Opie, J. Am. Chem. Soc. 64, 1084 (1942). 



40 U. V. Solmssen and J. Lee, U.S. Pat. 2,457,932 (Jan. 4, 1949). 



" A. Emmerie and C. Engel, Rec. irav. chim. 58, 283 (1939). 



« J. G. Baxter, Biol. Symposia 12, 484 (1947). 



« H. W. Rawlings, Oil & Soap 21, 257 (1944). 



" H. W. Rawlings, N. H. Kuhrt, and J. G. Baxter, /. Am. Oil Chemists' Soc. 25, 



24 (1948). 

 «M. Kofler, Helv. Chim. Acta 30, 1053 (1947). 

 46 M. L. Quaife, /. Biol. Chem. 175, 605 (1948). 

 "D. G. Chapman, P. Lichon, and J. A. Campbell, /. Am. Pharm. Assoc. Sci. Ed. 



40, 379 (1951). 



48 K. Ritsert, E. Merck's Jnhresher. 55, 13 (1943). 



49 T. Canback and B. Wallenberg, Svensk Farm. Tidskr. 50, 477 (1946). 

 ^o T. Moore and J. Tosic, Biochem. J. 37, xiv (1943). 



5' R. A. Dunford, Can. Chem. Process Inds. 35, 47 (1951). 

 52 E. Eden and V. H. Booth, Food ManuJ. 25, 279 (1950). 



