Identification of losartan degradates in stressed tablets by LC-MS and LC-MS/MS

Three unknown peaks were observed in the severely stressed losartan tablets (at 40 degrees C and 75% relative humidity for 3 years) analyzed by a stab ility indicating HPLC method. The sample solutions were subjected to liquid chromatography-tandem mass spectrometric (LC-MS/MS) analysis to obtain the chemical identities of these potential degradates. High accuracy and sensi tivity of losartan and its degradates were obtained by using atmospheric pr essure chemical ionization (APCI) technique in the LC-MS/MS analysis. Three trace level degradates (less than or equal to 0.1%) were found to be the a ldehyde and dimeric derivatives of losartan. The structural assignment was further confirmed by comparing the tandem mass spectra of the unknowns with those of the authentic materials of each corresponding degradate. Finally, the mechanistic pathways for the formation of the dimers are discussed. (C ) 1999 Elsevier Science B.V. All rights reserved.