The GC/MS analysis of some commonly used non-steriodal anti-inflammatory drugs (NSAIDs) in pharmaceutical dosage forms and in urine

All the commonly used non-steriodal anti-inflammatory drugs (NSAIDs), excep t mefenamic acid, when extracted from the pharmaceutical dosage forms or th e urines of users, and derivatized by silylation and then analysed by GC/MS , gave the mono- or the di-trimethylsilyl derivatives (depending on the num ber of derivatized groups in the drug) as the sole products. Mefenamic acid gave a mixture of products. When extracted from pharmaceutical dosage form s or from the urines of users, and analysed by GC/MS without derivatization , some of the NSAIDs were separated and detected as the unchanged molecules as the sole products, while others were separated and detected in altered forms as sole products or mixtures, depending on: (a) the solvent in which the extract was dissolved for injection into GC/MS, (b) the chemical struct ure of the drug, and (c) specifically for diflunisal, the presence or absen ce of potential methylating and/or acetylating agents on the GC column and/ or septum. The main thermally-induced reactions of the underivatized NSAIDs included (i) methyl ester formation at the COOH group when the extract was dissolved in methanol, (ii) decarboxylation (i.e., loss of CO2), (iii) deh ydration (i.e., loss of H2O) when the chemical structure permitted, such as for diclofenac, and (iv) cleavage at a carbon-heterocyclic nitrogen bond w hen one is present in an NSAID. Heating the urine in similar to 2 M HCl at 100 degrees C for 30 min, has been found to be a satisfactory means for eff ecting hydrolysis of the NSAIDs glucuronide conjugates. No metabolites, res ulting from aromatic-ring hydroxylation, have been detected in urine for an y of the NSAIDs studied. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.