62 
Biological  Standardisation. 
f  Am.  Jour.  Pharm. 
February,  19 17. 
a  practical  working  basis.  These  manufacturers  through  years  of 
experience  were  in  a  position  to  eliminate  the  nonessentials  and  to 
arrive  at  some  common  ground  by  compromise.  A  method  which 
under  certain  conditions  can  be  made  fairly  satisfactory  may  fail 
entirely  when  attempts  are  made  to  apply  it  under  practical  work- 
ing conditions. 
As  may  be  inferred  from  the  foregoing  introduction  it  is  the 
purpose  of  the  writer  to  point  out  certain  objectionable  features  in 
the  biological  assays  which  are  either  suggested  or  required  in  the 
9th  Revision  of  the  U.  S.  Pharmacopoeia  (2). 
We  will  assume,  as  the  Revision  Committee  evidently  did,  that 
a  biological  method  can  be  found  which  is  a  measure  of  therapeutic 
value. 
It  is  very  natural  that  opinions  should  differ  among  pharmacolo- 
gists as  to  which  reaction  more  nearly  represents  the  activity  of  a 
drug,  when  the  drug  has  a  number  of  apparently  different  thera- 
peutic uses. 
It  is  no  more  remarkable  that  differences  of  opinion  exist  as  to 
which  is  more  accurate,  if  several  assay  methods  are  available. 
One  can  expect  therefore  that  the  methods  adopted  would  be  sub- 
jected to  criticism,  for  in  this  way  only  can  errors  be  eliminated. 
The  Digitalis  Series  of  Heart  Tonics. 
The  method  adopted  for  the  assay  of  the  digitalis  series  of  heart 
tonics  is  that  known  as  the  one-hour  frog  heart  or  the  minimum  sys- 
tolic dose  (M.  S.  D.)  method. 
In  a  review  of  the  various  methods  in  use  Edmunds  and  Hale 
(3)  eliminated  most  of  them  as  illogical  or  inaccurate.  These 
authors  found  little  reason  for  choice  between  the  one  mentioned 
above  and  another  known  as  the  minimum  lethal  dose  (M.  L.  D.) 
method.1  Their  preference  inclined  toward  the  former  on  the  basis 
of  cost  and  time. 
This  method  leaves  much  to  be  desired  in  regard  to  accuracy  and 
dependability,  since  if  one  economizes  either  in  time  or  in  material  it 
is  usually  at  the  expense  of  accuracy. 
1  The  M.  L.  D.  or  minimum  lethal  dose  method  is  described  in  detail  by 
Houghton  and  Hamilton  (4).  The  M.  L.  D.  is  the  smallest  dose  per  gram 
weight  of  frog  which  kills  a  majority  of  the  test  animals,  the  correctness  of 
the  end  point  being  verified  by  observation  of  the  laid-bare  heart,  which  is  in 
systole,  if  death  is  due  to  the  uncomplicated  action  of  one  of  the  digitalis 
series. 
