Oxybutynin is an antimuscarinic agent used for the treatment of an overactive bladder. Because of its poor chromophore, it is difficult to determine oxybutynin by HPLC-UV analysis The difficulty increases when the analysis involves a complex biological matrix like plasma. Precolumn derivatization with trifluoroacetic anhydride followed by GC separation and ECD was used to solve this problem. The developed GC-ECD method had good linearity in the concentration range 2-20 ng ml-1 with a correlation coefficient of 0.9959. The accuracy and sensitivity for the determination of the halogenated derivative by this method was better than that for GC-MS. NMR and mass spectroscopy data confirmed the derivatization reaction. The developed GC-ECD method was used to study the pharmacokinetic parameters of an oxybutynin transdermal patch (36 mg/39 cm2) and oxybutynin gel (10% w/w). The Cmax, Tmax and AUC0-96 values for the oxybutynin transdermal patch and oxybutynin gel were equivalent. © 2014 The Royal Society of Chemistry.