Hydrochlorothiazide (6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7sulfonamide 1,1-dioxide) (HCTZ) 1 is a widely used diuretic and anti-hypertensive. Recently, the Pharmeuropa recognized a new impurity initially thought to be an HCTZ dimer 6, which consists of the active drug (HCTZ) linked via the former b-ring methylene to a known degradate, 5-chloro-2,4-disulfamylaniline 2. In an effort to meet a new requirement, an analytical high-pressure liquid chromatography method was developed that was selective and sensitive to the subject impurity. The impurity was concentrated and puriยฎed using a combination of solid phase extraction and reversephase high-pressure liquid chromatography. Subsequently, the impurity has been identiยฎed as a speciยฎc HCTZ-CH 2 -HCTZ isomer utilizing a variety of analytical techniques, including hydrolysis, ultraviolet spectroscopy, liquid chromatography/mass spectrometry, and 1 H and 13 C nuclear magnetic resonance (NMR) spectroscopy. The data resulting from the application of these analytical techniques conยฎrm the identity of the impurity as a methylene bridged pair of HCTZ molecules; however, a total of six possible isomers 7aยฑf exist because of the presence of three reactive amines/sulfonamides on each HCTZ molecule.