Development and validation of a UV-Spectrophotometric method using methanol for the simultaneous estimation of doxycycline and voriconazole in pharmaceutical formulations

Abstract

The development and validation of a UV-spectrophotometric method for the simultaneous estimation of doxycycline and voriconazole in pharmaceutical formulations are presented in this study. This method was designed to address the limitations of existing analytical techniques by providing a simple, accurate, and efficient approach suitable for routine quality control and therapeutic monitoring. Methanol was selected as the solvent, and estimation was done using the multiwavelength method of analysis. Estimation of doxycycline was done by recording a difference of absorbance at 358 and 402 nm while the estimation of voriconazole was done by recording absorbance difference at 428 and 463 nm. The difference of absorbance for estimation of two drugs is recorded for elimination of interference of the other drug. The method demonstrated excellent linearity, with calibration curves showing strong correlation coefficients. Accuracy was confirmed through satisfactory recovery rates, and precision was validated with %RSD values below 2% for both intraday and inter-day measurements. The method exhibited robustness and ruggedness, maintaining consistent performance under varying experimental conditions and across different analysts. Low limits of detection and quantification underscored the method's sensitivity. This UV-spectrophotometric method offers significant practical advantages, including reduced analysis time and cost-effectiveness, making it highly suitable for adoption in pharmaceutical laboratories. The study concludes that this method is a valuable tool for improving drug quality and safety, contributing to advancements in pharmaceutical sciences and supporting enhanced productivity in drug analysis.

Keywords

• Simultaneous estimation
• doxycycline
• voriconazole
• method validation
• UV-spectrophotometry

References

1. Muller PY, Milton MN. The determination and interpretation of the therapeutic index in drug development. Nat Rev Drug Discov. 2012;11(10):751-761. https://doi.org/10.1038/nrd3801
2. Mokhtari RB, Homayouni TS, Baluch N, Morgatskaya E, Kumar S, Das B, Yeger H. Combination therapy in combating cancer. Oncotarget. 2017;8(23):38022. https://doi.org/10.18632/oncotarget.16723
3. Azevedo MM, Teixeira-Santos R, Silva AP, Cruz L, Ricardo E, Pina-Vaz C, Rodrigues AG. The effect of antibacterial and non-antibacterial compounds alone or associated with antifungals upon fungi. Front Microbiol. 2015;6:669. https://doi.org/10.3389/fmicb.2015.00669
4. Eisen DP. Doxycycline. InKucers' the use of antibiotics 2017 Oct 2 (pp. 1204-1229). CRC Press. Spader TB, Venturini TP, Rossato L, Denardi LB, Cavalheiro PB, Botton SA, Santurio JM, Alves SH. Synergysm of voriconazole or itraconazole with other antifungal agents against species of Fusarium. Rev Iberoam Micol. 2013;30(3):200-204.https://doi.org/10.1016/j.riam.2013.01.002
5. Gupta D, Bhardwaj S, Sethi S, Pramanik S, Das DK, Kumar R, Singh PP, Vashistha VK. Simultaneous spectrophotometric determination of drug components from their dosage formulations. SpectrochimActa A MolBiomolSpectrosc. 2022 Apr 5;270:120819. https://doi.org/10.1016/j.saa.2021.120819
6. Musiol R, Mrozek-Wilczkiewicz A, Polanski J. Synergy against fungal pathogens: working together is better than working alone. Curr Med Chem. 2014 ;21(7):870-893. https://doi.org/10.2174/0929867321666131218094848.
7. Hoffman A, Stepensky D. Pharmacodynamic aspects of modes of drug administration for optimization of drug therapy. Crit Rev Ther Drug Carrier Syst. 1999;16(6): 571-639 https://doi.org/10.1615/CritRevTherDrugCarrierSyst.v16.i6.20
8. Ramesh PJ, Basavaiah K, Divya MR, Rajendraprasad N, Vinay KB, Revanasiddappa HD. Simple UV and visible spectrophotometric methods for the determination of doxycycline hyclate in pharmaceuticals. J Anal Chem. 2011;66:482-489. https://doi.org/10.1134/S1061934811050157

9. Kogawa AC, Salgado HR. Quantification of doxycycline hyclate in tablets by HPLC–UV method. J Chromatogr Sci. 2013;51(10):919-925.https://doi.org/10.1093/chromsci/bms190
10. Mitić SS, Miletić GŽ, Kostić DA, Nasković-Ðokić DČ, Arsić BB, Rašić ID. A rapid and reliable determination of doxycycline hyclate by HPLC with UV detection in pharmaceutical samples. J Serb Chem Soc. 2008;73(6):665- 671.https://doi.org/10.2298/JSC0806665M
11. Adams AI, Steppe M, Frehlich PE, Bergold AM. Comparison of microbiological and UV-spectrophotometric assays for determination of voriconazole in tablets. J AOAC Int. 2006;89(4):960-965. https://doi.org/10.1093/jaoac/89.4.960
12. Eiden C, Mathieu O, Peyrière H, Hillaire-Buys D, Cociglio M. Simultaneous quantification of voriconazole and its N- oxide metabolite in human plasma by an easy and rapid isocratic LC method with UV detection. Chromatographia. 2008;67:275-280.https://doi.org/10.1365/s10337-007-0508-z
13. Tamilselvi N, Hassan B, Fadul FB, Kondapalli D, Anusha K, Kurian DS. UV spectrophotometric estimation of voriconazole in tablet dosage form. Res J Pharm Technol. 2011;4(11):1791-1793.
14. Nováková L, Vlčková H. A review of current trends and advances in modern bio-analytical methods: chromatography and sample preparation. Anal ChimActa. 2009 ;656(1-2):8-35.https://doi.org/10.1016/j.aca.2009.10.004
15. Parmar A, Sharma S. Derivative UV-VIS absorption spectra as an invigorated spectrophotometric method for spectral resolution and quantitative analysis: Theoretical aspects and analytical applications: A review. TrAC Trends Anal Chem. 2016 ;77:44-53. https://doi.org/10.1016/j.trac.2015.12.004
16. Guideline ICH. Validation of analytical procedures: text and methodology. Q2 (R1). 2005 Nov;1(20):05.
17. Ingle RG, Zeng S, Jiang H, Fang WJ. Current developments of bioanalytical sample preparation techniques in pharmaceuticals. J Pharm Anal. 2022;12(4):517-529. https://doi.org/10.1016/j.jpha.2022.03.001
18. Patil KS, Chougale RD, Hajare AA. Development and validation of RP-HPLC method for estimation of camptothecin in mixed micelle formulation. Res J Pharm Technol. 2022;15(9):4248-4252. https://doi.org/10.52711/0974- 360X.2022.00714
19. Rakesh B, Bhargavi P, Reddy SR, Kumar AA. UV-Spectrophotometric method development and validation for the quantitative estimation of solifenacin succinate in tablets. Int J Pharm Pharm Sci. 2014;6:190-193.
20. da Silva AT, Brabo GR, Marques ID, Bajerski L, Malesuik MD, Paim CS. UV spectrophotometric method for quantitative determination of Bilastine using experimental design for robustness. Drug Anal Res. 2017;1(2):38- 43.https://doi.org/10.22456/2527-2616.79221
21. de Barros JO, Kogawa AC, Salgado HR. Short-term stability study of doxycycline tablets by high performance liquid chromatography, spectrophotometry in the ultraviolet region and turbidimetry. J Pharm SciExpPharmacol. 2017;2018:43-49.https://doi.org/10.29199/JPCT.101018
22. Bhairy S, Shaikh A, Nalawade V, Hirlekar R. Development and validation of bivariate UV-visible spectroscopic method for simultaneous estimation of curcumin and piperine in their combined nanoparticulate system. J Appl Pharm Sci. 2021;11(5):064-070.https://doi.org/10.7324/JAPS.2021.110509
23. Klimenko LY. Determination of linearity, accuracy and precision of UV-spectrophotometric methods of quantitative determination in forensic and toxicological analysis in the variant of the method of additions. Drug Anal Res. 2017;1(2):38-43.
24. Wei WZ, Zhu WH, Yao SZ. Application of robust regression in multicomponent UV spectrophotometry by direct calibration. Chemometrics and intelligent laboratory systems. 1993 ;18(1):17-26. https://doi.org/10.1016/0169- 7439(93)80041-F
25. Soni S, Ram V, Verma D, Verma A. Analytical method development and validation of metoprolol succinate by high performance liquid Chromatography and Ultraviolet spectroscopy technique. Res J Pharm Technol. 2021;14(2):931- 937. https://doi.org/10.5958/0974-360X.2021.00166.9
26. Sarkar M, Khandavilli S, Panchagnula R. Development and validation of RP-HPLC and ultraviolet spectrophotometric methods of analysis for the quantitative estimation of antiretroviral drugs in pharmaceutical dosage forms. J Chromatogr B. 2006;830(2):349-354.https://doi.org/10.1016/j.jchromb.2005.11.014