538  Assay  Methods  for  Tincture  of  Aconite.  { ^ecembe/w™' 
It  has  been  urged  that  lethal-dose  methods  do  not  measure  the 
therapeutic  value  of  drugs.  This  objection  may  be  valid  in  regard 
to  the  assay  of  such  a  drug  as  digitalis,  which  contains  several  im- 
portant active  principles  that  may,  theoretically,  decompose  into 
substances  that  are  highly  toxic  but  possess  no  therapeutic  value. 
With  aconite,  however,  the  matter  is  entirely  different.  Aconitine 
is  by  far  the  most  important  constituent,8  the  other  alkaloids  which 
may  be  present  contributing  little  or  nothing  to  the  physiological 
or  toxic  action  of  the  aconite  preparation.  Under  certain  condi- 
tions, aconitine  undergoes  decomposition,  but  the  resulting  products 
are,  relatively,  devoid  of  toxicity.  Therefore,  since  it  seems  safe 
to  consider  only  one  active  principle,  and  since  decomposition  of 
this  active  principle  leads  to  the  formation  of  substances  much 
less  toxic  and  also  much  less  active  therapeutically,  a  lethal-dose 
method  should  give  information  regarding  the  amount  of  this  sub- 
stance present  in  the  preparation  to  be  assayed. 
The  determination  of  the  lethal  dose  for  guinea-pigs  has  been 
commonly  accepted  as  the  most  trustworthy  method  for  the  physi- 
ological assay  of  aconite.  In  carrying  out  the  tests  according  to 
this  method,  the  tinctures  were  diluted  in  the  proportion  of  one 
part  of  tincture  to  three  parts  of  normal  salt  solution;  the  dose 
calculated  per  gramme  body  weight,  and  the  injections  made  sub- 
cutaneously.  The  animals  were  examined  at  intervals  over  24 
hours,  and  note  was  made  at  the  end  of  that  time  as  to  those  that 
survived  and  those  that  succumbed.  The  method  proved  very 
satisfactory,  in  so  far  that  the  lethal  dose  can  usually  be  determined 
with  considerable  accuracy,  and  it  is  not  common  for  pigs  to  die 
much  "  out  of  order,"  though  this  occasionally  occurs.  The  fol- 
lowing protocol  is  illustrative  of  the  results  obtained : 
Experiment  I.    Tincture  of  Aconite  A. 
Weight  of  Animal  Dose  in  Cc.  per  gram  body  weight  Results 
465  .00025  Survived. 
495  .00030  Survived. 
235  .00030  Died. 
240  .00030  Died. 
260  .00032  Died. 
The  final  results  secured  by  the  guinea-pig  method  are  given  in 
Table  IT. 
Preparation  M.  L.  D.  in  Cc.  per  gramme  body  weight 
Tincture  A   00033 
Tincture  B  00065 
Tincture  C   00065 
Tincture  D   00240 
