TITRATION OF BASES AND THEIR SALTS WITH PERCHLORIC-ACID IN ACETIC-ANHYDRIDE, GLACIAL ACETIC-ACID AND THEIR MIXTURE

The nonaqueous titration of 8 drugs in Japanese Pharmacopoeia was investigated in place of Kjeldahl's method and diazotization titration. The drugs were determined directly by potentiometric titration with perchloric acid in a mixture of acetic anhydride and glacial acetic acid. The titration curves (the first and second derivative curves after smoothing) were recorded on an automatic titrator assisted by a microcomputer. Urea (I), pyrazinamide (II), ethenzamide (III), acetaminophen (IV), neostigmine methylsulfate (V) and procaine hydrochloride (VII) were determined by titration in acetic anhydride. Ethyl p-aminobenzoate (VIII) was determined by titration in glacial acetic acid. Primidone (VI) was too weak a base to be determined by this method. The standard deviation of this method was 0.12% (VII) approximately 0.34% (III) and 0.92% (IV). Neostigmine bromide (X), however, reacted with 1 eq. perchloric acid, 3 mol of (V) reacted with 1 eq. perchloric acid since methylsulfate decomposed to methyl acetate and sulfuric acid. The basic center of pyrazinamide was determined to be both nitrogens of pyrazine owing to the high field shift of 3-C and 6-C on NMR by protonation.