Method development for Quantification of (S) - Isomer in Tenofovir Disoproxil Fumarate Bulk Drug and Formulations using Meta Substituted Phenyl Carbamate of Amylose as Chiral Selector
Abstract
The present paper involves developing a novel Chiral ultra-high performance liquid chromatographic (UPLC) technique for estimating Tenofovir Disoproxilfumarate (TDF) enantiomeric purity in both bulk and bulk dosage forms. The TDF is a pro drug employed in treating HIV in which the (R) isomer is active, while (S) isomer remains impurity and pharmacologically inactive. The UPLC method is categorized as a green chromatographic technique in which the chiral separation was achieved on ChiralpakIG-3(2.1x100mm) 3.0μm immobilized amylose column with meta substituted 3 chloro, 5 dimethyl phenyl carbamate as chiral selector, at a flow rate of 0.5ml/min using 0.5% diethylamine as an additive in hexane and ethanol. The influence of chiral additives and organic modifiers on enantio separation was investigated. The separation was analyzed on different columns for maximum resolution>10.0. The method was linear between within 0.25 to 7.5 μg.mL−1. The detection and quantification limits of (S) isomer were 0.08 μg.mL−1 and 0.25 μg.mL−1, respectively. Forced degradation studies were conducted and all the degradants were separated from drug peak. ICH guidelines validated the method.
Keywords:
Tenofovir Disoproxil fumarate, UPLC Method, CHIRALPAK-IG-3, Forced degradation and Validation.DOI
https://doi.org/10.25004/IJPSDR.2021.130405References
Neil MJO. Ed by the Merck Index-An Encyclopaedia of Chemicals, Drugs and Biological, Merck and Co. Inc, 2006.
Keamey BP, Flherty JF, Shah J. Tenofovir disoproxil fumarate: clinical pharmacology and Pharmacokinetics. ClinPharma-cokine.2004;43:595-612.
Fung HB, Stone EA, Piacenti FJ. Tenofovir disoproxil fumarate: a nucleotide reverse transcriptase inhibitor for the treatment of HIV infection. Clinical Therapeutics. 2002;24(10): 1515–1548.
Srinivas RV, Robbins BL, Connelly MC. Metabolism and in vitro antiretroviral activities of bis(pivaloyloxymethyl) prodrugs of acyclic nucleoside phosphonates. Antimicrobial Agents Chemother.1993; 37:2247–2250.
Balzarini J, Aquaro S, Perno CF. Activity of the (R)-enantiomers of 9-(2-phosphonylmethoxypropyl)-adenine and 9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine against human immunodeficiency virus in different human cell systems. Biochem Biophys Res Commun.1996; 219:337–341.
Balzarini J, Holý A, Jindrich J. Differential antiherpes virus and antiretroviral effects of the (S) and (R) enantiomers of acyclic nucleoside phosphonates: potent and selective in vitro and in vivo antiretroviral activities of (R)-9-(2-phosphonomethoxypropyl)-2, 6-diaminopurine. Antimicrobial Agents Chemother.1993; 37:332–338.
Nelson M, Portsmouth S, Stebbing J. An open-label study of Tenofovir in HIV-1 and Hepatitis B virus co-infected individuals. AIDS. 2003; 17:F7–F10.
Patel S, Baghel US, Rajesh P, Prabhakar D, Engla G, Nagar PN. Spectrophotometric method development and validation for simultaneous estimation of Tenofovirdisoproxilfumarate and Emtricitabine in bulk drug and tablet dosage form.International Journal of Pharmaceutical and Clinical Research. 2009;1(1):28–30.
Pendela M, Getu WK, Van den Mooter G, Baert L, Hoogmartens J, Adams E. LC assay for a HIV tablet containing emtricitabine, tenofovir disoproxil fumarate and rilpivirine. Chromatographia.2011; 73:439–445.
Raju NA, Begum S. Simultaneous RP-HPLC method for the estimation of the Emtricitabine, Tenofovir disoproxil fumarate and Efavirenz in tablet dosage forms. Res J of Pharm and Tech.2008; 1(4):522–525.
Jullein V, Treluyer JM, Pons G, Rey E. Determination of tenofovir in human plasma by high performance liquid chromatography with spectrofluorometric detection. J of Chrom B. 2003; 785:377–381.
Sentenac S, Fernandez C, Thullier A, Lechat P, Aymard G. Sensitive determination of tenofovir in human plasma samples using reverse phase liquid chromatography. J of Chrom B. 2003; 793: 317–324
Kandagal PB, Manjunatha DH, Seetharamappa J, Kalanur SS.RP-HPLC method for the determination of tenofovir in pharmaceutical formulations and spiked human plasma. Analytical Let.2008; 41(4):561–570.
King T, Bushman L, Kiser J, Anderson PL, Ray M, Delahunty T, Fletcher CV. Liquid Chromatography–tandem mass spectrometric determination of tenofovir-diphosphatein human peripheral blood mononuclear cells. J of Chrom B. 2006; 843:147–156.
Chantelle BH, Mary LC, Edward PA. Development of a sensitive and specific liquid chromatography/mass spectrometry method for the determination of tenofovir in human plasma. Rapid Comm in Mass Spec. 2007; 21:2087–2094.
Takahashi M, Kudaka Y, Okumura N, Hirano A, Banno K, Kaneda T. Determination of plasma tenofovir concentrations using a conventional LC-MS method. Bio and Pharm Bull. 2007; 30:1784–1786.
Joshi M, Nikalje AP, Shahed M, Dehghan M. HPTLC method for the simultaneous estimation of emtricitabine and tenofovir in tablet dosage form.Ind J of Pharm Sci. 2009; 71(1): 95–97.
Seshachalam U, Rajababu B, Haribabu B, Chandrasekhar KB. Enantiomeric separation of tenofovir on an achiral C18 column by HPLC using L-phenylalanine as a chiral mobile phase additive. J of Liq Chrom and Rel Tech. 2008;3(1–4):410–420.
Suresh Babu, Ravi Chandra Babu, Konda Reddy S. Development and validation of RP-chiral HPLC method for quantification of (S)-isomer in Tenofovir Disoproxil Fumarate. Int J of current Pharm Res.2017; 9(6):31-36.
Heydari R, Shamsipur M. Enantiomeric separation and quantification of Tenofovir Disoproxil Fumarate using amylose based chiral stationary phase by high performance liquid Chromatography. Acta Chromatographica.2015; 27(4):583-595.
Nov’akov’a L, Matysov’a L, Solich P. Advantages of application of UPLC in pharm analysis Talanta.2006; 68:908-918.
Swartz M. UPLC: An introduction and review. J of LiqChrom and Related Tech. 2005;28:1253-1263.
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