372 
Standardization  of  Drugs. 
j  Am.  Jour.  Pharm 
{     August,  1910. 
examined  and  the  tincture  and  the  infusion  gave  concordant  results 
indicating  that  3.5  mgs  equalled  1  cat  unit.  A  specimen  of  the 
Kombe  showed  exactly  half  the  activity  of  the  hispidus,  7  mgs. 
being  found  to  be  equal  to  a  cat  unit,  a  tincture  and  an  infusion 
being  likewise  examined.  Subsequently  an  authentic  specimen  of 
each,  obtained  from  Professor  Rusby,  was  examined,  the  seed  being 
finely  powdered  and  exhausted  by  heating  on  a  boiling  water  bath 
for  an  hour.  The  ratio  of  activity  of  the  infusions  was  the  same 
as  that  just  mentioned,  but  both  infusions  wTere  much  stronger  than 
we  had  anticipated  they  would  be,  and  1.5  mg.  of  the  hispidus  and 
3  mgs.  of  the  Kombe  were  found  to  be  equal  to  a  cat  unit.  The 
activity  of  this  specimen  of  hispidus  corresponds  to  about  12  per 
cent,  of  Merck's  amorphous  strophanthin — an  activity  that  has  been 
hitherto  unsuspected,  we  believe. 
Conclusions. — The  cat  affords  a  simple  method  of  standardizing 
the  drugs  of  the  digitalis  group.  This  method  is  available  for  the 
retail  pharmacist  who  will  devote  as  much  care  to  the  process  as  is 
required  in  the  chemical  assay  of  opium. 
The  cat  affords  a  means  of  comparing  the  activity  of  the  several 
digitalis  bodies  on  the  human  heart.  This  is  not  possible  on  the 
frog  by  present  methods. 
With  some  of  the  digitalis  bodies,  notably  digitoxin,  the  minimal 
lethal  dose  for  the  cat  by  the  vein  is  determined  more  conveniently 
by  injecting  about  one-half  of  the  lethal  dose  into  the  vein,  and 
after  an  interval  of  about  twenty  minutes,  injecting  crystalline  oua- 
bain (so-called  crystalline  strophanthin)  until  the  animal  dies. 
Crystalline  ouabain  is  capable  of  replacing  any  of  the  digitalis 
bodies  which  we  have  tested  so  far  as  the  direct  action  on  the  heart 
is  concerned,  that  is,  one-half  of  the  fatal  dose  of  any  of  these 
digitalis  bodies  and  one-half  of  the  fatal  dose  of  crystalline  ouabain 
will  cause  death  in  a  short  time  if  they  be  injected  into  the  femoral 
vein  in  the  manner  described. 
The  absorption  of  digitalis  and  of  strophanthus  from  the  alimen- 
tary canal  is  extremely  variable,  that  of  strophanthus  is  far  more 
variable  than  that  of  digitalis,  for  this  reason  the  activity  of  these 
drugs  cannot  be  fixed  by  means  of  the  oral  administration. 
Cumulation  occurs  with  digitalis  to  such  a  degree  that  no  conclu- 
sions can  be  drawn  regarding  activity  from  the  effects  on  animals 
which  have  been  used  previously  for  digitalis,  unless  many  weeks 
have  elapsed  since  the  previous  use. 
