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
作者： Mohit Thummar , Prinesh N. Patel , Arun L. Petkar , Debasish Swain , R. Srinivas
DOI: 10.1002/RCM.7842
关键词:
摘要: RATIONALE Saquinavir mesylate (SQM) is an antiviral drug used for the treatment of HIV infections. The identification and characterization all degradation products are essential achieving quality in pharmaceutical product development also patient safety. METHODS was subjected to hydrolytic (HCl, NaOH water), oxidative (H2 O2 ), photolytic (UV fluorescence light) thermal (dry heat) forced conditions as per ICH guidelines. best chromatographic separation (DPs) achieved on a CSH-Phenyl Hexyl column (100 × 2.1 mm, 1.7 μm) with ammonium acetate (10 mM, pH 5.0) methanol mobile phase gradient mode at flow rate 0.28 mL/min. RESULTS Nine DPs were obtained under various conditions. All characterized by using ultra-high-performance liquid chromatography/electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC/ESI-QTOF MS/MS) pathway justified mechanistic explanations. main formed amide hydrolysis, conversion into diastereomers, N-oxide dehydration well oxidation alcohol from drug. method validated can be control (QC) laboratory assure SQM bulk finished formulations. CONCLUSIONS A simple UHPLC/photodiode array (PDA) developed successfully transferred UHPLC/ESI-Q-TOF MS/MS DPs. Very interestingly, diastereomeric resolved method. Copyright © 2017 John Wiley & Sons, Ltd.
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