428 
The  Assay  of  Aconite. 
5  Am.  Jour.  Pharm. 
\      June,  1921. 
human  beings  as  one  that  will  kill  300  gm.  of  guinea  pig  in  a  dose  of 
two  milligrams.  On  this  question  pharmacologists  and  physiologists 
are  apt  to  divide  and  differ.,  As  lethal  dose  is  the  basis  used  in  physi- 
ological assay  methods,  it  is  probably  the  only,  and  hence  the  best 
basis  available  for  determining  relative  therapeutic  efficiency  of  the 
drug. 
Beginning  with  the  pure  aconitine  crystals  we  used  for  making 
our  hydrolysis  products  for  above  experiments  our  committee  sent 
out  samples  of  same  and  of  a  sample  of  fluidextract  aconite  to  the 
physiological  chemists  of  five  different  laboratories.  The  prime 
purpose  of  this  was  to  determine  whether  results  by  such  a  minimum 
lethal  dose  method  would  be  sufficiently  close  in  the  hands  of  varying 
laboratories  and  observers  to  warrant  hoping  to  utilize  it  in  an  assay 
method — assuming,  of  course,  that  minimum  lethal  dose  on  guinea 
pigs  would  be  a  basis  for  therapeutic  value.   The  results  follow: 
Aconitine  cryst. 
gm.  per  gm,  wt. 
of  guinea  pig.     F.  E.  Aconite  Rt. 
Sharp  &  Dohme  0000000625  0.000300 
Upjohn   0000000600  0.000266 
Parke  Davis  &  Co  0000000600  0.000300 
Eli  Lilly  &  Co  0000000625  0.000275 
Norwich  Pharmacal  Co.,    .0000000510  0.000360 
If  we  assume  that  minimum  lethal  dose  on  guinea  pigs  is  a  basis 
for  therapeutic  efficiency  of  aconite,  then  these  results  distinctly  in- 
dicate that  this  method  is  sufficiently  trustworhy  and  efficient  to  serve 
as  an  assay  method  to  determine  the  therapeutic  efficiency  of  aconite 
preparations  based  upon  pure  aconitine  crystallized  as  a  standard. 
The  Scientific  Section  of  the  American  Drug  Manufacturers' 
Association  hence  recommend  that  the  chemical  assay  be  dropped 
for  aconite  and  its  preparations  and  a  physiological  assay  based  upon 
aconitine  crystallized  U.  S.  P.  be  substituted  in  its  place. 
In  my  laboratory  the  m.  1.  d.  for  benzoyl-aconine  and  aconine 
were  also  determined  on  guinea  pigs  in  comparison  with  the  aconi- 
tine and  the  following  results  obtained: 
M.  L.  D.  Guinea  Pig. 
Aconitine  cryst   0.0000000625  gm.  per  gm.  wt.  of  guinea  pig. 
Benzoyl-aconine    0.00002  gm.  per  gm.  wt.  of  guinea  pig. 
Aconine    0.00025  gm.  per  gm.  wt.  of  guinea  pig. 
F.  E.  Aconite  Root  .  .    0.00003  &m-  Per  gm-  wt.  of  guinea  pig. 
