Enhancement of ampicillin partition behavior

Several ion-pair or adduct forming additives tha" enhanced ampicillin partition behavior were identified and evaluated. At pH 3, picric acid and trichloroacetic acid increased the ampicillin aqueous-octanol partition coefficient 250 and 30 times, respectively. At pH 7, quaternary compounds gave the most significant increases in the partition coefficient. Values for an aqueous pH 7 chloroform system increased from zero in the absence of additives to 2.28, 1.86, 1.82, and 1.70 for equimolar amounts of benzalkonium, tetraheptylammonium, benzethonium, and cetalkonium chlorides, respectively. Extraction of ampicillin from aqueous pH 7 solution was possible by adding a quaternary agent in an equimolar amount. However, extraction of ampicillin from plasma required large molar excesses. Tetraheptylammonium chloride was added at a molar concentration 10(3) times greater than that of the ampicillin. Plasma samples spiked at the 3-microgram/ml level gave 93% recovery (CV 6.7%, n = 16) when extracted three times. The extracts were quantitated by TLC.