Journal of Pharmaceutical and Biomedical Analysis 53 (2010) 287–294 Contents lists available at ScienceDirect Journal of Pharmaceutical and Biomedical Analysis journal homepage: www.elsevier.com/locate/jpba Stress degradation studies of nelfinavir mesylate by Fourier transform infrared spectroscopy Parul Singh a , Ranjana Mehrotra a,∗ , A.K. Bakhshi b a Optical Radiation Standards, National Physical Laboratory (Council of Scientific and Industrial Research), K.S. Krishnan Road, New Delhi 110012, India b Department of Chemistry, University of Delhi, Delhi 110007, India article info Article history: Received 16 January 2010 Received in revised form 21 March 2010 Accepted 23 March 2010 Available online 30 March 2010 Keywords: Nelfinavir mesylate Stress degradation ICH HIV protease inhibitors Fourier transform infrared spectroscopy abstract Nelfinavir mesylate is the first nonpeptidic protease inhibitor available in pediatric formulation. In the present paper the stability of nelfinavir mesylate under different stress conditions is evaluated using Fourier transform infrared spectroscopy. The drug is subjected to thermal degradation, photodegradation, acid hydrolysis, base hydrolysis and oxidation as per ICH guidelines. Differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD) and high performance liquid chro- matography (HPLC) are carried out to support the implementation of infrared spectroscopy for the stability studies of nelfinavir mesylate. Significant changes are observed in the IR spectra collected after exposing the drug to thermal radiations, acid and base hydrolysis and oxidative degradation. No change is observed in the spectra of the drug after exposing it to sunlight indicating the good photostability of nelfinavir mesylate. The results of infrared spectroscopy agree well with that of other complementary techniques as DSC, TGA, XRD and HPLC. © 2010 Elsevier B.V. All rights reserved. 1. Introduction Nelfinavir mesylate (mol. formula C 32 H 45 N 3 O 4 S·CH 4 O 3 S) is the first nonpeptidic protease inhibitor available in pediatric formulation. The molecule contains 5-chiral carbon (Fig. 1) and the drug substance is presented as a single isomer. The chemical name of the nelfinavir mesylate is [3S-[2(2S*,3S*),3,4a,8a]]- N-(1,1-dimethylethyl)decahydro-2-[2-hydroxy-3-[(3-hydroxy- 2-methylbenzoyl)amino]-4-(phenylthio)butyl]-3-isoquinoline carboxamide monomethanesulphonate (salt). The HIV pro- tease is an enzyme required for the proteolytic cleavage of the viral polyprotien precursors found in infectious HIV. Nelfinavir reversibly binds to the active site of the HIV protease and prevents it from cleaving the gag-pol polyprotien resulting in the formation of immature noninfectious viral particles [1]. Several reports are available on the simultaneous determination of nelfinavir mesylate with other protease inhibitors and nonnu- cleoside reverse transcriptase inhibitors using high performance liquid chromatography (HPLC) [2–8], ion pair HPLC [9], liquid chromatography–mass spectroscopy (LC–MS) [10] and HPLC–MS [11]. The determination of nelfinavir in bulk drugs and dosage form has been reported by some researchers [12–14]. Nelfinavir mesy- ∗ Corresponding author. E-mail addresses: ranjana@mail.nplindia.ernet.in, ranjanamehrotra@hotmail.com (R. Mehrotra). late was determined in the presence of its degradation products using high performance thin layer chromatography (HPTLC) [12]. Another stability indicating HPLC method was reported for the determination of nelfinavir mesylate as bulk drug and in pharma- ceutical dosage form [13]. Spectrophotometry [14,15], ultraviolet (UV) spectrophotometry [16], and potentiometry [17] methods have been described for the determination of nelfinavir mesylate. An evaluation of the liquid chromatography based international pharmacopeia’s method for the nelfinavir mesylate purity control was published by Yekkala et al. [18]. A reverse phase (RP) HPLC method has been described for the determination of nelfinavir mesylate in tablet dosage form [19]. More recently Seshachalam et al. [20] developed a stability indicating RP-LC method for the determination of nelfinavir mesylate and its related impurities in drug substances and pharmaceutical formulations. Stress testing provides information about degradation mech- anisms and potential degradation products. This information can be used to develop manufacturing processes or to select proper packaging. It may also help in preparing reference material for iden- tified degradation products. There is a need to develop a simple, fast and accurate method to determine the stability of drug substances under different stress conditions. Susceptibility to oxidation, acidic hydrolysis, base hydrolysis, thermal stability and photostability are some of the important stress conditions defined by ICH. In the present scenario infrared spectroscopic techniques are becoming increasingly important and popular in pharmaceutical industries because they are nondestructive in nature, can be applied 0731-7085/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.jpba.2010.03.030