Stability of selected chlorinated thiazide diuretics

Area of Science:

• * Sports Science
• * Analytical Chemistry
• * Anti-Doping

Background:

• * Diuretics, such as thiazides, are misused in sports for masking prohibited substances or rapid weight loss.
• * Thiazides are known to hydrolyze, forming aminobenzenedisulphonamide, but their stability under various conditions is not well-documented.
• * Limited data exists on the impact of pH, temperature, and light on thiazide stability.

Purpose of the Study:

• * To investigate the stability of chlorothiazide, hydrochlorothiazide, and altizide under varying pH, temperature, and light conditions.
• * To identify the degradation products formed from these thiazides.
• * To assess the implications for anti-doping analysis.

Main Methods:

• * Incubation of chlorothiazide, hydrochlorothiazide, and altizide at different pH levels (including pH 9.5) and temperatures (up to 60°C).
• * Exposure of samples to UV light.
• * Detection of degradation products using analytical methods.

Main Results:

• * The degradation product, aminobenzenedisulphonamide, was detected in all three thiazides after incubation at pH 9.5 and 60°C for 48 hours.
• * Lower pH and temperatures prevented detectable degradation for all compounds.
• * Altizide and hydrochlorothiazide photodegraded to chlorothiazide under UV light, with altizide being the most unstable compound.
• * Thiazide degradation products can form in urine during sample transport.

Conclusions:

• * Thiazide diuretics are unstable under specific conditions (alkaline pH, high temperature, UV light), forming detectable degradation products.
• * Altizide is the most susceptible to degradation among the tested compounds.
• * Anti-doping laboratories must incorporate testing for thiazide degradation products into routine analyses as mandated by the World Anti-Doping Agency (WADA).