AmMaSiP9of.rm*}      Standardization  of  Preparations.  117 
The  difficulty  of  standardizing  digitalis  preparations,  therefore, 
lies  in  the  fact  that  no  single  constituent  represents  the  entire  phys- 
iologic effect  of  the  drug.  But  this  is  not  the  only  case  of  that 
kind — we  have  many  drugs  with  which  this  condition  exists,  such, 
for  example,  as  strychnine  and  brucine  in  nux  vomica  ;  and  morphine, 
codeine,  narcotine,  etc.,  in  opium.  This  fact  has  not  deterred  us 
from  officially  adopting  an  assay  process  for  nux  vomica,  based  upon 
the  strychnine  content ;  for  opium,  based  upon  the  morphine  per- 
centage ;  and  for  cinchona,  based  upon  the  amounts  of  the  alkaloids 
relatively  more  soluble  in  ether,  namely:  quinine,  cinchonidine  and 
quinidine.  Why,  then,  should  we  not  consider  equally  valuable  an 
assay  process  for  digitalis  based  upon  the  percentage  of  its  most 
active  heart-stimulating  glucoside,  digitoxin  ?  May  it  not  be  that 
such  a  standardization  of  digitalis  will  prove  to  be  quite  as  accurate 
and  efficient  as  the  standardization  of  cinchona  bark,  based  upon 
the  percentage  of  ether-soluble  alkaloids  which  it  contains  ? 
The  object  of  this  joint  paper  is  to  throw  light  upon  that  ques- 
tion. We  shall  endeavor,  by  means  of  a  table  with  parallel  columns, 
to  show  that  a  fairly  constant  ratio  exists  between  the  chemical 
assay,  based  upon  the  single  constituent  digitoxin,  and  the  result  of 
the  physiological  test  on  standard  guinea-pigs,  which,  of  course,  is 
that  due  to  the  combined  effect  of  all  of  the  active  principles.  It 
is  not  necessary  that  the  constituent  which  is  determined  should 
possess  the  entire  activity  of  the  drug,  nor  is  it  claimed  to  be  so  in 
this  case.  It  is  only  necessary  that  the  amount  of  the  readily  deter- 
mined principle  bear  a  fairly  constant  ratio  to  the  combined  action 
of  all  of  the  drug  constituents,  in  order  to  make  such  an  assay  proc- 
ess valuable.  In  this  connection,  however,  Dr.  Robert  A.  Hatcher 
states  in  the  Journal  of  the  American  Medical  Association  for  Decem- 
ber 22,  1906,  in  referring  to  the  digitalis  glucosides,  that  "  digitoxin 
more  nearly  represents  the  leaf,"  and  that  "  despite  the  numerous 
disadvantages  of  digitoxin,  it  bids  fair  to  displace  digitalis  in  thera- 
peutics." While  I  do  not  believe  that  Dr.  Hatcher  has  given 
sufficient  consideration  to  the  great  disadvantage  of  the  insolubility 
of  digitoxin  in  neutral  media,  thereby  rendering  its  hypodermic  use 
impossible,  I  fully  agree  with  him  in  believing  that  digitoxin  is  by 
far  the  most  important  constituent  of  digitalis,  and  that  it  sufficiently 
nearly  represents  the  drug  to  enable  us  to  standardize  the  drug  by 
means  of  it. 
