216  Standardization  of  Officinal  Drugs.  {Am-&™*\m&vm' 
unlikely  that  the  variability  noted  in  gelsemium  is  due  to  the  same 
cause.  Of  the  effects  of  cultivation,  altitude,  climate,  character  of 
soil,  etc.,  we  as  yet  know  but  little.  It  is  also  pretty  certain  that 
drying  and  age  alter  materially  the  character  of  the  active  princi- 
ples. Again  our  knowledge  of  the  chemical  nature  of  the  active 
principles  of  most  drugs  is,  at  least,  very  uncertain,  and  in  many  we 
are  as  yet  unable  to  decide,  on  what  ingredient  the  activity  depends; 
as  for  example  cannabis  indica.  In  ergot  we  cannot  accept  the 
alkaloids  of  Wenzell,  Tanret  and  other  investigators  as  representing 
the  activity  of  the  drug.  In  the  great  bone  of  the  contention,  how- 
ever, the  important  solanaceous  drugs  we  are  confronted  with  a 
serious  difficulty.  Accepting  the  results  of  Ladenburg  we  find 
three  alkaloids  atropine,  hyoscyamine  and  hyoscine,  all  having 
the  same  forumla  C17HMN03,  but  these  same  alkaloids  vary  greatly 
physiologically.  No  process  of  assay  such  as  could  be  made  officinal 
would  serve  to  separate  the  hyoscyamine  from  atropine  in  bella- 
donna and  stramonium  or  hyoscine  from  hyoscyamine  in  hyoscya- 
mus.  According  to  some  recent  investigations  the  alkaloid  of 
belladonna  is  hyoscyamine  which  in  the  course  of  extraction  is  con- 
verted into  atropine.  Or  what  is  probably  true  is  that  the  composi- 
tion varies  with  the  age  of  the  root  or  season  when  collected. 
There  is  yet  room  for  a  thorough  scientific  study  of  the  subject. 
If  these  alkaloids  existed  in  nature  associated  in  a  definite  propor- 
tion an  estimation  of  total  alkaloids  would  be  sufficient. '  In  vera- 
trum  and  digitalis  we  are  confronted  by  analogous  conditions.  An 
assay  under  such  circumstances  can  certainly  be  of  little  value  in 
correcting  the  uncertainty  of  medical  practice.  While  admitting 
the  desirability  of  some  method  of  determining  the  medical  value 
of  such  powerful  drugs  an  attempt  to  standardize  such  would  result 
in  making  uncertainty  more  uncertain.  Our  foundation  is  too 
unstable  to  permit  the  rearing  of  a  fine  super-structure. 
The  alkaloidal  principles  are  associated  in  drugs  with  other 
organic  substances  such  as  resin,  coloring  matter,  tannin,  vegetable 
acids,  inert  alkaloids,  etc.,  and  it  is  frequently  difficult  to  separate 
the  active  principle  in  anything  like  a  pure  condition  in  a  single  opera- 
tion. Frequently  it  requires  several  additional  purifications  before 
it  can  be  satisfactorily  determined.  It  certainly  would  be  a  serious 
error  to  estimate  the  percentage  of  alkaloid  from  the  weight  of 
crude  residue  obtained,  yet  this  is  recommended  in  some  of  the 
