The novel acid degradation products of losartan: Isolation and characterization using Q-TOF, 2D-NMR and FTIR

• Forced degradation of losartan in acidic condition.
• Isolation and characterization of degradation product.
• Structural elucidation using LC-QTOF-MS, 1D/2D NMR.
• Identification of positional dimers.

Forced degradation of losartan potassium in acidic condition resulted into three potential unknown impurities. These unknown degradation products marked as LD-I, LD-II and LD-III were analyzed using a new reverse-phase high performance liquid chromatography (HPLC), eluting at 3.63, 3.73 and 3.91 relative retention times with respect to losartan potassium (LOS) peak. All three were isolated from reaction mass using preparative HPLC and their structures were elucidated using LC–MS/MS, multidimensional NMR and FTIR spectroscopic techniques, as 52,112-dibutyl-54,114-dichloro-11H,51H,71H,111H-1(5,1),7(1,5)-ditetrazola-5,11(1,5)-diimidazola-2,8(1,2),3,9(1,4)-tetrabenzenacyclododecaphane,(Z)-52,112-dibutyl-54,114-dichloro-11H,51H,72H,111H-1(5,1),7(2,5)-ditetrazola-5,11(1,5)-diimidazola-2,8(1,2),3,9(1,4)-tetrabenzenacyclododecaphane, and 52,112-dibutyl-54,114-dichloro-12H,51H,72H,111H-1(5,2),7(2,5)-ditetrazola-5,11(1,5)-diimidazola-2,8(1,2),3,9(1,4)-tetrabenzenacyclododecaphane, respectively. To best of our knowledge, all three degradation products are novel impurities which are not discussed at any form of publication yet.

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