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Identification of degradation products of saquinavir mesylate by LC-MS: Molecular docking and in silico ADME prediction studies
* 1 , 1 , 1 , 2 , 1
1  School of Pharmacy, Anurag Group of Institutions, Venkatapur (V), Ghatkaser (M), Medchal (D), Hyderabad- 500 088, Telangana, India-500 088
2  Department of Pharmaceutics, Mother Theresa College of Pharmacy, Edulabad(V), Ghatkaser (M), Medchal (D), Telangana, India-500 088

Published: 03 November 2018 by MDPI in 4th International Electronic Conference on Medicinal Chemistry session ECMC-4

Saquinavir mesylate (SQM) is subjected to forced degradation under conditions of hydrolysis, oxidation, dry heat, photolysis as recommended by International Conference on Harmonization guideline Q1A (R2). In total, (I-V) degradation products (DPs) were formed in acidic hydrolytic, alkaline hydrolytic and oxidative conditions. Successful separation of SQM and its DPs was achieved on C18(4.6mm×75mm) 3.5µg column at ambient temperature (30˚C) with mobile phase A (10mM ammonium acetate in water), B100% acetonitrile at 2.0ml/min flow rate in the gradient mode. The injection volume was fixed at 20µl and detection wavelength at 238nm. The HPLC method was found to be linear, accurate, precise, sensitive, specific, rugged, and robust for quantification of SQM as well as degradation products. The major degradation products (DP-1) formed under hydrolytic acid conditions were identified and characterized by LC-MS/MS. Further, DP-1 were isolated through column chromatography and analyzed by 1H NMR. In silico molecular docking studies on HIV protease (PDB: 4qgi) for DPs and SQM as well as prediction of toxicity and ADME properties were performed.

Keywords: Saquinavir mesylate, Degradation Products, HPLC, 1H NMR, Mass Spectra, Molecular Docking, Toxicity