Abstract An HPLC method was developed to determine the stability of alprazolam (AL) as a pure drug and in monodrug pharmaceutical tablets. The main degradation product of AL tablets was isolated and fully characterized as triazolaminoquinoleine (TAQ). For a quantitative evaluation of the excipient effects in the pharmaceutical formulations, a 2 k fractionated factorial design was applied in the preparation of the different samples. The kinetic of degradation of AL in each formulation was followed by UV spectrophotometry. It was found that excipients like CMC and magnesium stearate favour degradation, while the rate of the reaction is decreased when lactose and starch were used as excipients. A mechanism for the interactions of AL with some excipients is postulated that explains the observed results. Copyright © 2009 John Wiley & Sons, Ltd.