XXIX] DRUGS 353 



CAFFEIN and ACETPHENETIDIN fPHENACETIN) IN MIXTURES. 



5 PREPARATION OF SAMPLE AND SOLUTION.-TENTATIVE. 



In the case of preparations containing acetphenctidin instead of acetanilid, but 

 otherwise identical, make the gross separation of the caffein-acetphenetidin mix- 

 ture as directed under 1 . 



6 CAFFEIN.-TENTATIVE. 



Treat the chloroform extract, obtained as directed under 1, with 10 cc. of sul- 

 phuric acid (1 to 10) and digest on a steam bath until the liquid is reduced to about 

 5 cc. Dilute with 10 cc. of water and continue the digestion until the volume is 

 again reduced to 5 cc, then add 10 cc. of water and continue heating until the 

 residual liquid amounts to 8-10 cc. If, during the digestion, particles of acet- 

 phenctidin remain on the sides of the flask rinse them into the solution vnth a few 

 drops of chloroform. 



Great care must also be given to the degree of evaporation. Should the aqueous- 

 acid solution and suspension of caffein-acetphenetidin be concentrated far beyond 

 the limits indicated, more or less phenetidin sulphonate is likely to be formed, 

 which later resists acetylization and conversion to acetphenctidin. 



Cool and transfer with water to a separatory funnel, so that the final volume does 

 not greatly exceed 20 cc. Then proceed as directed under 3. 



7 ACETPHENETIDIN.-TENTATIVE. 



Wash the filter, used to dry the chloroform in 6, with 5 cc. of water, receiving the 

 te r in the separatory funnel containing the solution of phenetidin sulphate. 

 Treat with successive small portions of solid sodium bicarbonate until, after com- 

 plete neutralization of free acid, an excess of the former remains at the bottom of the 

 mixture. Add 50 cc. of chloroform and for every 0.10 gram of acetphenetidin, known 

 or believed to have been present, 5 drops of acetic anhydrid; shake vigorouslj', allow 

 to clear, then withdraw the chloroform into a second separatory funnel containing 

 5 cc. of water. Shake this mixture and, after clearing, pass the solvent through a 

 small, dry filter into a 200 cc. Erlenmeyer flask. Distil over about 40 cc. of the 

 chloroform, make up the distillate to 50 cc. with chloroform, add this to the mate- 

 rial in the first separatory funnel and extract again. Withdraw the chloroform 

 layer to the second separatory funnel, wash and distil about 50 cc.(for use in the 

 final extraction). Distil the chloroform down to about 10 cc, transfer with sufficient 

 fresh solvent to a tared 50 cc. beaker or crystallizing dish, evaporate on the steam 

 bath to apparent dryness, finally removing any considerable e.xcess of acetic anhy- 

 drid by repeated additions of 1 cc. of chloroform and a drop of alcohol. The re- 

 formed acetphenetidin should finalh* appear as a whitish, crystalline mass with 

 a faint, acetous odor which disappears completely on standing some hours in the 

 open, or in a vacuum desiccator over lime. Weigh from time to time until the 

 final weight differs from the preceding by not more than 0.5 mg. 



CAFFEIN AND ANTIPYRIN IN MIXTURES'. 



8 PREPARATION OF SAMPLE AND SOLUTION.-TENTATIVE. 



(a) Extract a weighed portion of the finely powdered sample on a filter with 

 chloroform to separate the caffein and antipyrin from the usual excipients of tab- 

 let and pill combinations. Distil off the greater part of the chloroform and evap- 

 orate the remainder on the steam bath. 



