Am  jour  Pharm.)        Titration  of  Certain  Alkaloids.  657 
Sept.,  1921.       y  J  ' 
in  color  over  a  definite  range^of  hydrogen  ion  concentration — that  is 
to  say,  the  change  of  color  of  an  indicator  is  brought  about  by  hy- 
drogen ions,  and  what  we  are  actually  doing  when  we  bring  a  solu- 
tion to  the  neutral  point  of  methyl  orange,  say,  is  to  bring  it  to  a  defi- 
nite hydrogen  ion  concentration.  Therefore,  if  we  add  methyl 
orange  to  our  morphine  titration  and  bring  the  solution  to  the  neu- 
tral point  we  are  bringing  the  solution  to  a  hydrogen  ion  concentra- 
tion of  about  xPh  =  4,  or,  if  we  use  cochineal,  to  about  Ph  =  6. 
Now  if  the  hydrogen  ion  concentration  of  a  solution  of  morphine 
hydrochloride  of  the  strength  used  in  the  titration  is  Ph  =  4, 
methyl  orange  will  give  a  correct  result;  if  Ph  =  6,  cochineal  will 
give  a  correct  result;  but  they  cannot  both  give  a  correct  result.  It 
is  necessary,  therefore,  in  order  to  find  the  best  indicator  for  use 
in  any  given  titration,  to  determine  the  hydrogen  ion  concentration 
of  a  solution  of  the  end  product  of  the  titration  of  the  same  strength 
as  that  produced  in  the  titration.  Then  if  we  can  find  an  indicator 
which  has  its  color  change  at  this  hydrogen  ion  concentration,  that 
indicator  (other  things  being  equal)  should  be  the  best  for  use  in 
that  titration. 
TITRATION   OF  MORPHINE. 
The  B.  P.  recommends  methyl  orange  for  the  titration  of 
morphine;  the  U.  S.  P.  advises  cochineal.  In  Allen's  "Commercial 
Organic  Analysis,"  Vol.  V,  page  376,  we  find:  "Morphine  forms 
salts  which  are  perfectly  neutral  in  reaction  to  litmus  and  methyl 
orange,  and  hence  it  may  be  titrated  with  accuracy  by  the  aid  of 
standard  hydrochloric  acid  and  either  of  these  indicators." 
Experiments  were  therefore  carried  out  in  order  to  find  the 
hydrogen  ion  concentration  of  pure  morphine  hydrochloride  in  1 
per  cent,  solution,  which  is  about  the  strength  most  frequently  em- 
ployed in  a  titration. 
Pure  morphine  was  prepared  from  ordinary  pure  morphine 
hydrochloride  by  twice  crystallizing  from  a  dilute  slightly  alkaline 
solution  saturated  with  ether.  The  crystals  were  dried  and  ren- 
dered anhydrous  by  heating  at  115°. 
1  Ph  is  the  logarithm  of  the  reciprocal  of  the  hydrogen  ion  concentration 
in  terms  of  normal,  i.  e.,  if  Ph  =  1  the  hydrogen  ion  concentration  is  N/10. 
If  Ph  =  2,  N/100,  etc.  The  lower  the  value  of  Ph  the  more  acid  is  the  solu- 
tion and  vice-versa.   At  the  point  of  absolute  neutrality  Ph  =  7. 
