410 VITAMIN K GROUP 



substance by the American Medical Association.^^ Although one-half as 

 potent as the methylnaphthoquinone, 2-methyl-l,4-naphthohydroquinone 

 diacetate might serve as a better standard. ^^ Both of these compounds are 

 cheaply and easily prepared in a high state of purity, which can be tested 

 conveniently by means of melting point. The melting point of methylnaph- 

 thoquinone should be 105 to 106°, that of the diacetate 112 to 113°. The di- 

 acetate has the advantage of greater stability when mixed in the diet; 

 this, however, is of little or no importance for oral administration. For 

 convenience the methylnaphthoquinone I-7 unit will be used for expressing 

 comparative activities, with the caution that this unit may not represent 

 any fixed proportion of activity to weight units of vitamins Ki or K2 (Table 

 III). 



TABLE III 



Activities of Certain Antihemorrhagic Compounds Based on Chick 5-Day 

 Assays and Expressed in 2-Methyl-1,4-Naphthoquinone Units per 



Milligram 



Compound Units per milligram 



2-Methyl-l,4-naphthoquinone (menadione) 1000 



2-Methyl-l,4-naphthohydroquinone diacetate 450 



2-Methyl-4-amino-l-naphthol hydrochloride 500 

 2-Methyl-l,4-naphthohydroquinone diphosphoric acid ester (tetraso- 500 



dium salt, hexahydrate) 



2,3-Dimethyl-l,4-naphthoquinone 25 



2-Methyl-3-phytyl-l,4-naphthoquinone (vitamin Ki) 500 



2-Methyl-3-difarnes3'l-l,4-naphthoquinone (vitamin K2) 400 



2-Methyl-3-phytyl-l,4-naphthohydroquinone diacetate 170 



During the phases of isolation, purification, and synthesis the different 

 laboratories employed different assay methods and different standards or 

 units of potency which served their temporary purposes. These methods 

 and standards or units have been reviewed by Ansbacher.^^ 



7. Comparison of Assays by Different Methods 



Several of the present methods when carefully adhered to will yield 

 equivalent results. Repeated assays of 2-methyl-l,4-naphthohydroquinone 

 diacetate have all indicated that the potency of this compound is close to 

 one-half that of the methylnaphthoquinone.^' An average of relative values 

 obtained in other assays, as reviewed by Dam,^ leads to the same conclusion. 



'« Council on Pharmacy and Chemistry, J. Am. Med. Assoc. 116, 1054 (1941). 



37 D. T. Ewing, J. M. Vandenbelt, and O. Kamm, /. Biol. Chem. 131, 345 (1939). 



38 S. Ansbacher, /. Nutrition 21, 1 (1941). 



