Am.  Jour.  Pharm. 
June,  1921. 
The  Assay  of  Aconite. 
427 
both  cases  the  end  product  was  represented  by  ether  soluble  alkal- 
oids. We  have  shown  that  the  ether  soluble  alkaloids  are  not  all 
aconitine,  but  represent  a  inore  or  less  variable  proportion  of  aconi- 
tine  and  its  products  of  hydrolysis  benzoyl-aconirie  and  aconine.  This 
variability  alone  makes  the  assay  process  of  little  value  as  an  abso- 
lute standard  of  therapeutic  efficiency  and  as  well  makes  its  relative 
or  comparative  value  more  or  less  of  an  uncertain  quantity. 
In  order  to  determine  definitely  if  the  three  alkaloids  which  con- 
stitute the  ether  soluble  alkaloids — aconitine,  benzoyl-aconine  and 
aconine  could  be  separated  from  one  another  by  chemical  means  a 
supply  of  pure  aconitine  was  procured  and  hydrolized  into  benzoyl- 
aconine  and  some  of  the  latter  hydrolized  further  into  aconine. 
After  thus  coverting  a  number  of  grammes  in  this  way  and  obtain- 
ing a  quantity  of  each  of  benzoyl-aconine  and  aconine  in  pure  con- 
dition, attempts  were  made  to  determine  if  varying  solubility  in  all 
available  solvents  or  precipitation  by  all  known  precipitants  might 
give  a  method  of  separating  them  when  contained  in  a  mixture.  The 
result,  however,  was  that  no  method  was  discovered  by  which  they 
could  be  quantitatively  separated,  as  they  showed  similar  solubilities 
and  precipitation  by  precipitants.  It  was,  therefore,  decided  that  a 
chemical  separation  quantitatively  was  not  feasible  and  that,  there- 
fore, the  so-called  chemical  method  of  assay  was  not  possible,  pro- 
vided our  aim  was  to  get  as  the  end-product  of  our  assay  only  aconi- 
tine. 
It  was  also  determined  by  animal  experiments  that  benzoyl- 
aconine  and  aconine  do  not  possess  the  therapeutic  properties  of 
aconitine  and  their  lethal  dose  was  quite  far  removed  from  that  of 
aconitine. 
Hence  the  final  conclusion  reached  was  that  the  present  chem- 
ical assay  of  aconite  for  ether  soluble  alkaloids  was  misleading  and 
untrustworthy  and  had  better  be  abandoned, 
The  next  part  of  our  problem  was  to  see  if  a  physiological  assay 
could  be  developed  which  would  be  of  some  real  value  in  determin- 
ing approximately  correctly  the  therapeutic  efficiency  of  aconite  and 
its  preparations.  This,  of  course,  at  once  opens  up  the  question  as 
to  the  correctness  of  a  method  of  assay  which  has  as  its  criterion  and 
basis  the  lethal  dose  or  the  amount  that  will  kill  a  definite  weight  of 
animal  per  gram.  Or  in  simple  form  is  lethal  power  a  basis  for  thera- 
peutic efficiency,  and  is  one  drug  that  will  kill  300  gm.  of  guinea 
pig  in  a  dose  of  one  milligram  twice  as  efficient  therapeutically  upon 
