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A desimple-tailed study of the rate of interaction of citrate buffers with aniline to form anilides and imides shows that the basic mechanism follows essentially that previously described. Results show in particular that the rate of anhydride formation by the polycarboxylic acid is faster than from the previously studied succinic system and probably involves both the undissociated acid and its singly charged anion. The overall equilibria and rates for the total reaction were determined and the approach to equilibria checked with an analog computer. The speed and nature of the reaction suggest that these interactions may often be responsible for loss of activity of some drugs formulated with this buffer.

Tartaric acid buffer has been shown to form a reactive intermediate in aqueous solution capable of rapidly acylating any nucleophilic compound present. With aniline as the nucleophile, the rate of formation of the intermediate, presumably an acid anhydride, has been found to proceed at roughly the same rate as that of succinic acid but slower than citric acid. Only the monoanilide was obtained in appreciable amount.