Abstract
Objective: A simple, accurate and economical reverse phase- high performance liquid chromatographic method has been developed for the simultaneous quantitative estimation of two anti-retro viral drugs, Etravirine and Elvitegravir in nanoparticulate formulations for the first time. This method is a novel analytical technique for the detection of the both the drugs concurrently, as there is no method available for their simultaneous quantification, to the best of our knowledge.
Methods: Optimization and validation of the chromatographic conditions were completed according to the standard ICH guidelines. The separation was done on a C18 column (250 mm x 4.6mm, 5μm) using methanol and phosphate buffer of pH (5.6) as the mobile phase in the ratio 78:22 v/v at a flow rate of 1ml/min for a short run time of 13 min. The detection wavelength was 285nm and the column temperature was maintained at 32oC. Results: The developed method was linear over 10 to 160 µg/ml with a regression coefficient of 0.999 for each. The LOD values were 4.83 and 9.25 µg/ml while LOQ values were 14.63 and 28.01 µg/ml for etravirine and elvitegravir respectively. The recovery values obtained by etravirine and elvitegravir were between 97.6% and 100.8%. Conclusion: The method was specific, precise, fast and accurate with good inter and intra day precision. The method was also effectively employed for the characterization and simultaneous quantification of both drugs in nanoparticulate formulation.Keywords: Etravirine, elvitegravir, HPLC, nanoformulation, AIDS, anti-retro virals.
Graphical Abstract
[1]
Das, M.K.; Sarma, A.; Chakraborty, T. Nano-ART and NeuroAIDS. Drug Deliv. Transl. Res., 2016, 6(5), 452-472.
[3]
Taiwo, B.; Hicks, C.; Eron, J. Unmet therapeutic needs in the new era of combination antiretroviral therapy for HIV-1. J. Antimicrob. Chemother., 2010, 65(6), 1100-1107.
[4]
Abbott, N.J.; Patabendige, A.A.K.; Dolman, D.E.M.; Yusof, S.R.; Begley, D.J. Structure and function of the blood-brain barrier. Neurobiol. Dis., 2010, 37(1), 13-25.
[5]
Abbott, N.J. Blood-brain barrier structure and function and the challenges for CNS drug delivery. J. Inherit. Metab. Dis., 2013, 36(3), 437-449.
[6]
Ramana, L.N.; Anand, A.R.; Sethuraman, S.; Krishnan, U.M. Targeting strategies for delivery of anti-HIV Drugs. J. Control. Release, 2014, 192, 271-283.
[7]
Kumari, A.; Yadav, S.K.; Yadav, S.C. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surfaces. B Biointerfaces, 2010, 75, 1-18.
[8]
Tosi, G.; Costantino, L.; Ruozi, B.; Forni, F. Polymeric nanoparticles for the drug delivery to the central nervous system. Expert Opin. Drug Deliv., 2008, 5(2), 155-174.
[9]
Barakat, N.S.; Taleb, D.A. Bin; Salehi, A.S. Al. Target nanoparticles : An appealing drug delivery platform. J. Nanomedic. Nanotechnol., 2012, S4, 009.
[10]
Usach, I.; Melis, V.; Peris, J-E. Non-nucleoside reverse transcriptase inhibitors: a review on pharmacokinetics, pharmacodynamics, safety and tolerability. J. Int. AIDS Soc., 2013, 16, 1-14.
[11]
Tseng, A.; MacArthur, R.D. Profile of etravirine for the treatment of HIV infection. Ther. Clin. Risk Manag., 2010, 6(1), 49-58.
[12]
Lazzarin, A.; Campbell, T.; Clotet, B.; Johnson, M.; Katlama, C.; Moll, A.; Towner, W.; Trottier, B.; Peeters, M.; Vingerhoets, J.; de Smedt, G.; Baeten, B.; Beets, G.; Sinha, R.; Woodfall, B. Efficacy and safety of TMC125 (Etravirine) in treatment-experienced HIV-1-Infected patients in DUET-2: 24-Week results from a randomised, double-blind, placebo-controlled trial. Lancet, 2007, 370(9581), 39-48.
[13]
Elvitegravir @ pubchem.ncbi.nlm.nih.gov
https://pubchem.ncbi. nlm.nih.gov/compound/Elvitegravir#section=Mechanism-of-Action
[14]
Wills, T.; Vega, V. Elvitegravir: A once-daily inhibitor of hiv-1 integrase. Expert Opin. Investig. Drugs, 2012, 21(3), 395-401.
[15]
Tian, Y.; Zhang, L.; Shen, J.; Wu, L.; He, H.; Ma, D.L.; Leung, C.H.; Wu, W.; Fan, Q.; Huang, W.; Wang, L. An individual nanocube-based plasmonic biosensor for real-time monitoring the structural switch of the telomeric G-Quadruplex. Small, 2016, 12(21), 2913-2920.
[16]
Liu, L-J.; Wang, W.; Huang, S-Y.; Hong, Y.; Li, G.; Lin, S.; Tian, J.; Cai, Z.; Wang, H-M.D.; Ma, D-L.; Leung, C-H. Inhibition of the Ras/Raf interaction and repression of renal cancer xenografts in vivo by an Enantiomeric Iridium(III) metal-based compound. Chem. Sci., 2017, 8(7), 4756-4763.
[17]
Lin, S.; Gao, W.; Tian, Z.; Yang, C.; Lu, L.; Mergny, J-L.; Leung, C-H.; Ma, D-L. Luminescence switch-on detection of protein tyrosine kinase-7 using a G-Quadruplex-selective probe. Chem. Sci., 2015, 6(7), 4284-4290.
[18]
Wang, M.; Mao, Z.; Kang, T-S.; Wong, C-Y.; Mergny, J-L.; Leung, C-H.; Ma, D-L. Conjugating a groove-binding motif to an Ir(III) complex for the enhancement of G-Quadruplex probe behavior. Chem. Sci., 2016, 7(4), 2516-2523.
[19]
Damle, M.; Damle, M.C.; Road, K. Determination of etravirine in human plasma by HPLC. Indo Am. J. Pharm., 2017, 4(6), 1657-1664.
[20]
Runja, C.; Pigili, R.K. Development and validation of uv-spectroscopic method for estimation of niacin in bulk and pharmaceutical dosage form. J. Appl. Pharm. Sci., 2017, 3(4), 291-294.
[21]
Kommavarapu, P.; Maruthapillai, A.; Palanisamy, K. Preparation, characterization and evaluation of elvitegravir-loaded solid lipid nanoparticles for enhanced solubility and dissolution rate. Trop. J. Pharm. Res., 2015, 14(September), 1549-1556.
[22]
Swetha, P.; Prasad, V.; Raju, M.B.; Kumar, N.S. Estimation of elvitegravir in tablet dosage forms by RP-HPLC. Indo Am. J. Pharm. Res., 2013, 3(6)
[23]
Abobo, C.V.; Wu, L.; John, J.; Joseph, M.K.; Bates, T.R.; Liang, D. LC-MS/MS determination of etravirine in rat plasma and its application in pharmacokinetic studies. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2010, 15(878), 3181-3186.
[24]
Schöller-Gyüre, M.; Kakuda, T.N.; Sekar, V.; Woodfall, B.; De Smedt, G.; Lefebvre, E.; Peeters, M.; Hoetelmans, R.M. Pharmacokinetics of darunavir/ritonavir and TMC125 alone and coadministered in HIV-negative volunteers. Antivir. Ther., 2007, 12(5), 789-796.
[25]
Boffito, M.; Winston, A.; Jackson, A.; Fletcher, C.; Pozniak, A.; Nelson, M.; Moyle, G.; Tolowinska, I.; Hoetelmans, R.; Miralles, D.; Gazzard, B. Pharmacokinetics and antiretroviral response to darunavir/ritonavir and etravirine combination in patients with high-level viral resistance. Aids, 2007, 21(11), 1449-1455.
[26]
Schöller-Gyüre, M.; Kakuda, T.N.; De Smedt, G.; Vanaken, H.; Bouche, M.P.; Peeters, M.; Woodfall, B.; Hoetelmans, R.M.W. A pharmacokinetic study of etravirine (TMC125) co-administered with ranitidine and omeprazole in HIV-negative volunteers. Br. J. Clin. Pharmacol., 2008, 66(4), 508-516.
[27]
Simiele, M.; Ariaudo, A.; De Nicolo, A.; Favata, F.; Ferrante, M.; Carcieri, C.; Bonora, S.; Di Perri, G.; D’Avolio, A. UPLC-MS/MS method for the simultaneous quantification of three new antiretroviral drugs, dolutegravir, elvitegravir and rilpivirine, and other thirteen antiretroviral agents plus cobicistat and ritonavir boosters in human plasma. J. Pharm. Biomed. Anal., 2017, 138, 223-230.
[28]
Ramanathan, S.; Kakuda, T.N.; Mack, R.; West, S.; Kearney, B.P. Pharmacokinetics of elvitegravir and etravirine following coadministration of ritonavir-boosted elvitegravir and etravirine. Antivir. Ther., 2008, 13(8), 1011-1017.
[29]
Liu, C.; Xue, D.; Qin, X.; Li, X.; Tang, J.; Cao, L.; Xu, X.; Liu, Y.; Chen, Z. Development and validation of stability-indicating UPLC method for 9-Desmethyl-α-Dihydrotetrabenazine. Chromatographia, 2017, 80(10), 1589-1595.
[30]
Gousuddin, M.; Sengupta, P.; Chatterjee, B.; Das, S.K. Stability-indicating RP-HPLC method for simultaneous quantitation of tramadol and aceclofenac in presence of their major degradation products: method development and validation. J. Liq. Chromatogr. Relat. Technol., 2017, 40(17), 887-893.
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