Fast drug stability determination by LC variable-parameter kinetic experiments Giuseppe Alibrandi a, *, Salvatore Coppolino b , Santi D’Aliberti a , Rita Ficarra b , Norberto Micali c , Antonino Villari b a Dipartimento di Chimica Inorganica, Chimica Analitica e Chimica Fisica, Universita ` di Messina, Salita Sperone 31, Villaggio S. Agata, 98166 Messina, Italy b Dipartimento Farmaco-Chimico, Facolta ` di Farmacia, Universita ` di Messina, Villaggio Annunziata, Messina, Italy c Istituto di Tecniche Spettroscopiche, CNR, Via La Farina 237, 98100 Messina, Italy Received 24 April 2002; received in revised form 7 June 2002; accepted 19 June 2002 Abstract Variable-parameter kinetic experiments were carried out using HPLC as analytical instrument. The hydrolysis of aspirin was followed both at variable-temperature and at variable-pH conditions. The peak areas relative to salicylic acid were processed by direct fit to a mathematical model and/or by differential method obtaining, by single experiments, the values of the apparent rate constant in the whole range of temperature and pH studied. The results, although the discontinuity of this kind of analysis, are in agreement with those obtained by constant-parameter kinetics but saving experimental time. # 2003 Elsevier Science B.V. All rights reserved. Keywords: Variable-parameter kinetics; Variable-temperature kinetics; Variable-pH kinetics; HPLC; Aspirin; Hydrolysis 1. Introduction The effect of environmental parameters on the stability of drugs in solution is a vitally important information in pharmaceutical industry. It often requires a detailed kinetic investigation on new molecules of interest before its release on the market, to have quantitative data on the depen- dence of the reaction rate constant on tempera- ture, pH, ionic strength, metal ions concentration, etc [1]. This gives technical useful data on the time the species maintains its chemical identity in specified conditions and, more deeply, a panora- mic picture of the reactive behaviour useful for mechanistic studies. The usual way consists of following many times the reaction, by a suitable analytical instrument, in pseudo-first order condi- tions, for different values of a parameter and for each parameter enquired. Variable-parameter ki- * Corresponding author. Tel.: 39-090-39-3537; fax: 39- 090-39-3756. E-mail address: alibrandi@chem.unime.it (G. Alibrandi). Journal of Pharmaceutical and Biomedical Analysis 32 (2003) 1073  /1079 www.elsevier.com/locate/jpba 0731-7085/03/$ - see front matter # 2003 Elsevier Science B.V. All rights reserved. doi:10.1016/S0731-7085(03)00211-5