534 
Methods  for  Digitalis  Assay. 
Am.  lour.  Pharm. 
August,  1920. 
It  is  commonly  assumed  that  Newcomb  uses  the  Hatcher  Method 
without  material  change  from  that  first  published,  and  this  opinion 
will  perhaps  prevail  until  some  published  account  of  his  work  ap- 
pears. Unofficially,  however,  certain  statements  have  been  made 
such  as  these:  "Hatcher's  method,  without  modification,  is  of 
little  value."  "The  cat  is  the  least  important  part  of  the  method." 
"The  important  part  of  the  method  is  the  observation  of  the  action 
of  digitalis  on  the  bundle  of  His." 
One  may  assume,  therefore,  that  Newcomb  discredits  Hatcher's 
Method  in  which  the  death  of  the  cat  is  the  deciding  factor  and 
pins  his  faith  on  observing  the  heart  block  which  follows  fatigue 
of  the  auriculo-ventricular  bundle.  This  is,  to  a  limited  extent, 
characteristic  of  digitalis  poisoning  and  so  may  be  regarded  as  a 
valuable  feature  to  distinguish  the  character  of  the  poisoning,  but  it 
adds  nothing  to  the  accuracy  of  the  only  quantitative  features  which 
the  test  possesses,  namely,  the  M.  L.  D.  (minimum  lethal  dose). 
As  a  qualitative  test  this  feature  is  admirable;  but  no  pharma- 
cologist has  succeeded  in  making  the  test  an  accurate  quantitative 
one  unless  as  yet  unpublished. 
The  M.  S.  D.  Frog-heart  Method — the  Pharmacopoeial  method — 
is,  in  brief,  to  inject  the  diluted  preparation  into  the  abdominal 
lymph  sac  of  the  frog,  injecting  them  in  series  of  three  and  at  the 
end  of  one  hour  exposing  the  heart  to  observe  its  condition.  The 
end-point  is,  that  at  the  end  of  the  one-hour  period,  the  heart  must 
be  stopped  in  systole  while  the  next  smaller  dose — a  difference  not 
to  exceed  lo  per  cent. — ^leaves  the  heart  beating  at  that  time.  This 
method  has  two  advantages  over  those  employing  mammals,  namely, 
that  a  sufficient  number  of  test  animals  can  be  used  to  detect  and 
exclude  those  more  or  less  resistant  than  the  average  and  to  test 
the  standard  on  a  number  of  similar  animals  under  exactly  the  same 
conditions  of  weight,  age,  temperature  and  season,  all  of  which  may 
be  variants.  It  has  the  further  advantage  that  the  end-point  can 
be  recognized  as  being  due  to  one  of  the  digitalis  series  and  to  no 
other  poison  by  the  position  of  the  heart  in  systole. 
It  has  the  advantage  over  Newcomb's  modification  of  Hatcher's 
method  in  the  greater  accuracy  in  the  end-point  by  having  a  large 
number  of  test  animals  from  which  to  exclude  those  of  exceptional 
resistance — either  high  or  low. 
The  M.  L.  Frog-heart  Method  has  for  its  end-point  the  mini- 
mum lethal  dose — the  smallest  dose  causing  death  with  heart  in  systole. 
