Stability of selected chlorinated thiazide diuretics

In sports, diuretics are used for two main reasons: to flush previously taken prohibited substances with forced diuresis and in sports where weight classes are involved to achieve acute weight loss. A common property observed for thiazides is hydrolysis in aqueous media resulting in the formation of the degradation product aminobenzenedisulphonamide. This degradation product can be observed for several thiazides. Because there is limited information regarding the effect of pH, temperature and light on the stability of thiazides, these parameters were investigated for chlorothiaizide, hydrochlorothiazide and altizide. For all three compounds the degradation product could be detected after incubation at pH 9.5 for 48h at 60 degrees C. At lower pH and temperature the degradation product could not be detected for all compounds. When samples were exposed to UV-light altizide and hydrochlorothiazide were photodegraded to chlorothiazide. When the degradation rate between the different compounds was compared for a given temperature and pH, altizide is the most unstable compound. This study confirms that thiazide degradation products can be formed in urine during transport. Hence doping control laboratories shall include them into their routine testing methods as required by WADA.