^""^  ASgus^rS. }         Methods  for  Digitalis  Assay.  529 
THE  BIOLOGIC  METHODS  I^OR   DIGITALIS  ASSAY.* 
By  Herbert  C.  HamiIvTon. 
detroit,  mich. 
There  are  many  steps  in  the  process  of  transforming  the  lovely 
old-fashioned  flowering  plant,  fox-glove,  into  the  powerful  medicinal 
product  known  as  the  digitalis  heart  tonic.  In  fact,  some  of  the 
steps  might  be  called  stopping  places  and  regarded  as  of  more  than 
passing  interest;  especially  such  points  as  the  selection  of  some 
one  out  of  the  many  varieties  of  digitalis  to  be  the  official  one,  the 
choice  of  the  portion  of  the  plant  to  be  used,  the  age  of  the  plant, 
and  the  menstruum  for  extraction.  The  seriousness  of  these  prob- 
lems may  be  judged  by  the  last  mentioned,  since  the  U.  S.  P. 
Revision  Committees  have,  on  each  occasion,  selected  a  different 
menstruum  for  extracting  the  crude  drug. 
But  of  all  the  problems  demanding  attention,  probably  no  one 
has  received  more  than  that  of  proper  means  of  testing  and  stand- 
ardizing the  crude  drug  and  its  extracts.  From  the  time  of  Fagge 
and  Stevenson's  work^  recorded  in  1866  up  to  the  present  time, 
the  controversy  has  raged  unceasingly. 
These  investigators  first  used  the  method  later  modified  and  known 
as  the  Focke  method^  by  which  the  frog  was  injected  in  the  thigh,  the 
heart  exposed  and  the  time  noted  when  the  heart  stopped  in  systole. 
Koppe,  in  1875,^  studied  the  action  on  warm-blooded  animals, 
noting  the  effect  on  the  heart  but  especially  the  amount  necessary 
to  induce  vomiting.  This  was  later  suggested  by  Hatcher''  as  a 
means  of  standardization. 
Bennefeld,^  in  1881,  in  his  careful  examination  of  tinctures  of 
digitalis  from  different  parts  of  Germany,  selected  the  method  later 
known  as  the  Hatcher  Cat  Method,^  the  diluted  preparation  being 
slowly  injected  into  the  vein  of  a  rabbit  until  death  occurred. 
Bardet,^  in  1889,  used  the  frog  in  the  way  later  suggested  by 
Houghton,  that  is,  comparing  activities  on  the  basis  of  the  mini- 
mum lethal  dose. 
Houghton,^  in  1898,  first  published  the  method  and  described 
the  exact  technic  by  which  to  standardize  the  digitalis  prepara- 
tions. The  method,  at  time  of  publication,  had  actually  been  in 
practice  for  three  years  and  is  the  first  recorded  attempt  not  merely 
*Paper  read  at  the  St.  Louis  meeting  of  the  A.  C.  S.  and  published  by  courtesy 
of  the  American  Chemical  Society. 
