title: Identification of degradation products of saquinavir mesylate by ultra-high-performance liquid chromatography/electrospray ionization quadrupole time-of-flight tandem mass spectrometry and its application to quality control.
abstract: BACKGROUND
  Saquinavir mesylate (SQM) is an antiviral drug used for the treatment of HIV infections. The identification and characterization of all degradation products are essential for achieving the quality in pharmaceutical product development and also for patient safety.
  
  
  METHODS
  The drug was subjected to hydrolytic (HCl, NaOH and water), oxidative (H2O2), photolytic (UV and fluorescence light) and thermal (dry heat) forced degradation conditions as per ICH guidelines. The best chromatographic separation of the drug and all degradation products (DPs) was achieved on a CSH-Phenyl Hexyl column (100 × 2.1 mm, 1.7 μm) with ammonium acetate (10 mM, pH 5.0) and methanol as mobile phase in gradient mode at a flow rate of 0.28 mL/min.
  
  
  RESULTS
  Nine DPs were obtained under various forced degradation conditions. All the DPs were characterized by using ultra-high-performance liquid chromatography/electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC/ESI-QTOF MS/MS) and the degradation pathway of the drug was justified by mechanistic explanations. The main DPs were formed by amide hydrolysis, conversion into diastereomers, an N-oxide and dehydration as well as oxidation of the alcohol from the drug. The method was validated and can be used in a quality control (QC) laboratory to assure the quality of SQM in bulk and finished formulations.
  
  
  CONCLUSIONS
  A simple UHPLC/photodiode array (PDA) method was developed and successfully transferred to UHPLC/ESI-Q-TOF MS/MS for the identification and characterization of DPs. Very interestingly, diastereomeric DPs were obtained and successfully resolved by the chromatographic method. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, 500037, Telangana, India.
authors.forename: Mohit
authors.initials: M
authors.lastname: Thummar
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, 500037, Telangana, India.
authors.forename: Prinesh N
authors.initials: PN
authors.lastname: Patel
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, 500037, Telangana, India.
authors.forename: Arun L
authors.initials: AL
authors.lastname: Petkar
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, 500037, Telangana, India.
authors.forename: Debasish
authors.initials: D
authors.lastname: Swain
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, 500037, Telangana, India.|National Centre for Mass Spectrometry, CSIR - Indian Institute of Chemical Technology, Hyderabad, 500 007, Telangana, India.
authors.forename: R
authors.initials: R
authors.lastname: Srinivas
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, 500037, Telangana, India.
authors.forename: Gananadhamu
authors.identifier: http://orcid.org/0000-0002-6389-5994
authors.initials: G
authors.lastname: Samanthula