LC, LC-MS/MS studies for the identification and characterization of degradation products of hydrochlorothiazide and establishment of mechanistic approach towards degradation

The objective of the present investigation was to separate, identify and characterize the degradation products of hydrochlorothiazide under hydrolytic, oxidative, photolytic and thermal stress conditions as per the International Conference on Harmonization (ICH) guideline Q1A (R2). The drug degraded under acidic, basic, neutral and oxidative stress, while it was stable under photolytic and thermal stress conditions. Two degradation products were formed, which were separated by using HPLC on C18 column using isocratic elution program. A complete mass fragmentation pathway of the drug was first established with the help of LC-MS/MS studies. The stressed samples were subjected to LC-MS studies. The obtained mass spectral data were employed to characterize the degradation products and assign structures. The degradation products were identified as 4-amino-6-chloro-1,3-benzenedisulfonamide and 6-chloro-2-oxy-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide.