Am.  Jour.  Pharm.  ) 
August,  1920.  j 
Methods  for  Digitalis  Assay. 
533 
favorable  consideration.  The  gold  fish,  however,  is  exceedingly 
sensitive  to  substances  not  always  recognized  as  poisons  and  cer- 
tainly not  in  the  same  class  with  digitalis.  While  the  chances  of  a 
foreign  and  more  toxic  substance  being  found  with  digitalis  are 
remote,  they  are  always  possibly  present  as  every  manufacturer 
knows.  Without  a  confirmatory  test,  the  gold  fish  M.  L.  D.  method 
is  to  be  classed  as  questionable. 
The  guinea  pig  method  is  no  less  open  to  question  on  the  same 
score,  although  the  results  obtainable  purely  on  toxicity  are  quite 
uniform  and  accurate.  In  this  instance,  also,  there  is  no  observable 
reaction  characteristic  of  digitalis  either  before  or  after  death; 
and  death  often  results  from  respiratory  paralysis  rather  than  a 
direct  action  of  digitalis  on  the  heart. 
The  method  is  simple  and  as  described  by  the  authors  inexpensive, 
since  the  intention  is  to  use  guinea  pigs  already  used  for  another 
purpose  for  which  they  no  longer  are  eligible,  and  therefore  with  a 
value  theoretically  nil. 
Injection  is  made  subcutaneously  and  results  recorded  after  a 
definite  period.  Results  show  that  pigs,  while  fairly  uniform,  have 
individual  variations  as  well  as  seasonal,  but  these  can  be  eliminated 
as  factors  in  the  assay,  by  the  occasional  test  of  the  standard  and 
by  the  use  of  a  number  of  pigs  to  obtain  the  average  M.  L.  D. 
The  Hatcher  Cat  Method  seems  to  have  even  less  to  recommend 
it  since  there  is  nothing  characteristic  of  digitalis  in  the  death  of  the 
animal  and  further  its  inaccuracies  have  been  the  subject  of  comment 
by  several  authors.  Hatcher*^  noted  that  in  some  cases,  cats  re- 
quired a  dose  of  50  per  cent  larger  than  the  average  M.  L.  D. 
Robinson  and  Wilson^ found  in  a  series  of  ten  cats  that  the  M.  L. 
D.  ranged  from  70  to  210  per  cent,  of  the  average  M.  L.  D.  Eck- 
ler^^  found  a  variation  of  over  100  per  cent,  in  the  M.  L.  D.  of  cats. 
The  details  first  published  by  Hatcher  for  the  assay  of  digitalis 
required  that  the  immediate  cause  of  death  should  be  ouabain, 
only  a  part  of  the  M.  L.  D.  was  to  be  brought  about  by  the  digitalis. 
The  cat  is  partly  anesthetized  in  order  to  open  a  vein  into  which  is 
inserted  a  glass  canula.  Through  this  the  injection  is  made  slowly 
over  a  stated  period.  The  animal  must  die  in  less  than  90  minutes. 
The  method  has  been  modified  by  most  investigators,  especially 
by  those  who  found  any  valuable  feature  in  it. 
The  only  radical  change,  however,  is  that  made  use  of  by  New- 
comb  of  the  Pharmacy  Department  of  the  University  of  Minnesota. 
