Hydrolysis of fatty acid esters of acetaminophen in buffered pancreatic lipase systmes I.

A series of fatty acid esters of acetaminophen were prepared beginning with acetate, the propionate, and all even-numbered fatty acids and going through the octadecanoate. The enzymatic hydrolysis of all derivatives was studied in vitro with varying amounts of lipase assed to the hydrolysis mixtures. Under the conditions of the in vitro hydrolysis, it was observed that all derivatives were hydrolyzed more readily in an aqueous medium at pH 7.8. A positive relationship was seen between the hydrolysis rates and the concentration of lipase at this pH. There was a negative relationship between the chain length of the acyl moiety and the corresponding hydrolysis rates. The short chain esters were hydrolyzed at rates many times more rapid than the long chain esters. The intermediate chain-lenght ester, p-acetamidophenyl decanoate, p-acetamidophenyl laurate, and p-acetamidophenyl myristate, were hydrolyzed at intermedediate time periods extending over 12 hr, approaching completion at 97.5, 87.5, and 80.5%, respectively, when 18 Wilson units of lipase was used in each milliliter of hydrolysis mixture. The longer chain esters, p-acetamidophenyl palmitate and p-acetamidophenyl stearate, were hydrolyzed to the extent of 16 and 8%, respectively, over 12 hr under the same in vitro conditions.