Paracetamol esters, hydrolysis

The esters of PAABA reflect the pattern observed for the esters of paracetamol but the hydrolysis rates are much lower, apart from the alkyl esters which have similar rates of hydrolysis to the paracetamol esters in plasma and liver. 

EC oxidation is commonly employed in the analysis of some basic drugs, especially morphine and related opioids (Chapter 6, Section 1). Even if a compound is not amenable to EC oxidation, its metabolites may be. Phase I metabolism of aromatic xenobiotics often proceeds with aromatic hydroxylation. Hydrolysis of phenolic esters, reduction of diazo double bonds to primary amines and other reactions also occur. EC detection is not widely used to measure acidic or neutral compounds, such as salicylate or paracetamol after overdosage, since these compounds, although easily oxidised, are normally present at relatively high concentrations and UV detection is adequate. However, EC methods may be useful in measuring the plasma concentrations of these compounds attained after a single oral dose. ... 

Examples of substances that are prone to hydrolysis are acetylsalicylic acid, ampicillin, barbiturates, chloramphenicol, chlordiazepoxide, cocaine, corticosteroid phosphate or succinate esters, proteins, folinic acid, indomethacin, local anaesthetics, paracetamol (acetaminophen), pilocarpine, tropa alkaloids (atropine, scopolamine), xylomethazoline and the antimicrobial preservatives methyl and propyl parahydroxybenzoate. In the field of oncology, melphalan and bendamustine hydrochloride are highly susceptable to hydrolysis with a shelf life of 1.5 h for melphalan and 3.5 h for bendamustine at room temperature. 

Under addic conditions (pH 1) at room temperature, aspirin hydrolyses in a few horns whereas paracetamol can be stored at room temperature rmder acidic conditions (pH 1) for many days without much hydrolysis occurring. We will return to the properties of esters and amides in a little more detail in Chapters 3 and 4. 

A variation on the basic hydrolysis process is transesterifl-cation which is a widespread process in biological systems (c.f. the action of aspirin, choline esterase inhibitors and phosphorylation of proteins) but can also occur in vitro. In this case, the ester transfers the acyl group to the base carrying out the hydrolysis. Thus, for instance, if the base is paracetamol, as has been observed in mixtures of aspirin and paracetamol, acetylated paracetamol is produced (Fig. 5.38). 

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