A  janJuaUry  1909 m" }      Analysis  of  Headache  Mixtures.  5 
The  residue,  obtained  on  distilling  off  the  chloroform  and  consist- 
ing of  caffeine  and  acetanilid,  is  heated  with  sulphuric  acid  in  order 
to  change  the  acetanilid  into  aniline  sulphate,  the  caffeine  extracted 
with  chloroform  and  weighed,  and  the  aniline  sulphate  titrated  with 
a  solution  of  standard  potassium  bromide-bromate,  substantially  as 
has  been  described  by  Riedel  in  some  work  on  carbolic  acid  and 
on  aniline. 
In  mixtures  containing  acetphenetidin  in  place  of  acetanilid,  the 
procedure  is  similar  in  every  way  to  that  just  outlined  for  the  pre- 
ceding mixture,  with  the  one  exception  that  the  phenetidin  sul- 
phate formed  in  the  operation  cannot  be  titrated,  as  is  done  in  the 
case  of  aniline  sulphate,  but  is  by  means  of  acetylization  converted 
back  to  acetphenetidin  and  as  such  weighed. 
The  problem  becomes  somewhat  more  complicated  when  both 
acetanilid  and  acetphenetidin  are  present  in  the  same  mixture,  and 
it  required  diligent  search  to  discover  a  satisfactory  basis  of  separa- 
tion. The  sodium  bicarbonate  and  caffeine  may  be  eliminated  in 
the  manner  already  described.  The  resulting  sulphates  of  aniline 
and  phenetidin  are  converted  to  acetanilid  and  acetphenetidin  re- 
spectively and  the  mixture  treated  with  iodine  and  potassium  iodide 
in  the  presence  of  an  acid.  An  iodine  addition  product  of  acetphe- 
netidin is  formed,  practically  insoluble  in  the  liquids  used.  It  may 
be  filtered  off  and  made  to  yield  the  acetphenetidin  held  in  combi- 
nation, or  the  iodine  absorbed  in  the  reaction  is  determined  volu- 
metrically.  The  acetanilid  is  found  in  the  filtrate  from  the  acetphenet- 
idin compound  and  can,  after  suitable  treatment,  be  extracted  with 
chloroform  and  titrated  with  bromide-bromate  of  potassium  as  pre- 
viously noted.  This  method  of  separating  acetanilid  and  acetphenet- 
idin is  proving  exceedingly  useful  in  the  hands  of  the  Bureau 
workers,  affording  as  it  does,  a  rapid  and  convenient  check  on  acet- 
phenetidin sophistication. 
When  headache  mixtures  contain,  in  addition  to  the  synthetics 
just  considered,  cinchona,  coca  or  opium  alkaloids,  laxative  princi- 
ples and  other  extractive  matter,  their  analysis  sometimes  presents 
problems  not  at  all  easy  of  solution,  so  that  one  is  required  to  develop 
an  analytical  procedure  applicable  only  to  the  particular  case  in  hand. 
