DoE Experimental design in HPLC separation of pharmaceuticals; a review

DoE in HPLC drug analysis

  • Jevrem Stojanović University of Belgrade – Faculty of Pharmacy, Department of Drug Analysis
  • Jovana Krmar University of Belgrade – Faculty of Pharmacy, Department of Drug Analysis https://orcid.org/0000-0002-5469-9633
  • Ana Protić University of Belgrade – Faculty of Pharmacy, Department of Drug Analysis https://orcid.org/0000-0002-6304-1913
  • Bojana Svrkota University of Belgrade – Faculty of Pharmacy, Department of Drug Analysis
  • Nevena Đajić University of Belgrade – Faculty of Pharmacy, Department of Drug Analysis https://orcid.org/0000-0003-4420-9781
  • Biljana Otašević University of Belgrade – Faculty of Pharmacy, Department of Drug Analysis
Keywords: design of experiments, drug analysis, high pressure liquid chromatography, analytical method development and validation

Abstract


Design of Experiments (DoE) is an indispensable tool in contemporary drug analysis as it simultaneously balances a number of chromatographic parameters to ensure optimal separation in High Pressure Liquid Chromatography (HPLC). This manuscript briefly outlines the theoretical background of the DoE and provides step-by-step instruction for its implementation in HPLC pharmaceutical practice. It particularly discusses the classification of various design types and their possibilities to rationalize the different stages of HPLC method development workflow, such as the selection of the most influential factors, factors optimization and assessment of the method robustness. Additionally, the application of the DoE-based Analytical Quality by Design (AQbD) concept in the LC method development has been summarized. Recent achievements in the use of DoE in the development of stability-indicating LC and hyphenated LC-MS methods have also been briefly reported. Performing of Quantitative structure retention relationship (QSRR) study enhanced with DoE-based data collection was recomended as a future perspective in description of retention in HPLC system.

References

Ahuja S. Overview of modern pharmaceutical analysis. Sep. Sci. Technol. 2011;10:1-9.

Watson D. Pharmaceutical Analysis 5th Ed: A Textbook for Pharmacy Students and Pharmaceutical Chemists. Edinburgh: Churchill Livingstone; 2020; p. 480.

Lobrutto R, Patel T. Method validation in Kazakevich Y, Lobrutto R,(ed). HPLC for pharmaceutical scientists. 1st ed. John Wiley & Sons, Inc. 2007; p. 455-502.

Vogt FG, Kord AS. Development of quality-by-design analytical methods. J Pharm Sci. 2011;100(3):797-812.

Mattrey FT, et al. Current challenges and future prospects in chromatographic method development for pharmaceutical research. TrAC-Trend Anal Chem. 2017;95:36-46.

Baczek T. Computer-assisted optimization of liquid chromatography separations of drugs and related substances. Curr Pharm Anal. 2008;4(3):151-161.

Ganorkar SB, Shirkhedkar AA. Design of experiments in liquid chromatography (HPLC) analysis of pharmaceuticals: Analytics, applications, implications and future prospects. Rev Anal Chem. 2017;36(3):1-43.

Sahu PK, et al. An overview of experimental designs in HPLC method development and validation. J. Pharm. Biomed. Anal. 2018;147:590-611.

Komsta Ł, et al. J. Chemometrics in chromatography. CRC Press. 2018.

Stojanović B. Factorial-based designs in liquid chromatography. Chromatographia. 2013;76(5-6):227-240.

Hibbert DB. Experimental design in chromatography: a tutorial review. J Chromatogr B. 2012;910:2-13.

Leardi R. Experimental design in chemistry: A tutorial. Anal Chim Acta. 2009;652(1-2):161-172.

Hadjmohammadi MR, Ebrahimi P. Optimization of the separation of anticonvulsant agents in mixed micellar liquid chromatography by experimental design and regression models. Anal Chim Acta. 2004;516(1-2):141-148.

Vemić A, et al. Chaotropic agents in liquid chromatographic method development for the simultaneous analysis of levodopa, carbidopa, entacapone and their impurities. J Pharm Biomed Anal. 2013;77:9-15.

Dejaegher B, Heyden YV. Ruggedness and robustness testing. J Chromatogr A. 2007;1158:138-157.

Heyden VY, et al. Guidance for robustness/ruggedness tests in method validation. J Pharm Biomed Sci. 2001;24:723-753.

Debrus B, et al. Application of new methodologies based on design of experiments, independent component analysis and design space for robust optimization in liquid chromatography. Anal Chim Acta. 2011;691(1-2):33-42.

Ferreira SLC, et al. Statistical designs and response surface techniques for the optimization of chromatographic systems. J Chromatogr A. 2007;1158(1-2):2-14.

Bezzera MA, et al. Response surface methodology (RSM) as a tool for optimization in analytical chemistry. Talanta. 2008;76: 965-977.

Attimarad M, et al. Validation of rapid RP-HPLC method for concurrent quantification of amlodipine and celecoxib in pure and formulation using an experimental design. Microchem J. 2020;152:104365.

Dalvi AV, et al. Design of experiments-based RP–HPLC bioanalytical method development for estimation of Rufinamide in rat plasma and brain and its application in pharmacokinetic study. J Chromatogr B. 2018;1102:74-82.

Panda SS, et al. Analytical procedure development: Concept to application for chemometry based ultrafast LC estimation of pimavanserin in pharmaceuticals. J Liq Chromatogr R T. 2020;43(3-4):118-130.

Yabré M, et al. Development of a green HPLC method for the analysis of artesunate and amodiaquine impurities using Quality by Design. J Pharm Biomed Anal. 2020; 190: 113507.

Brereton RG. Chemometrics–data analysis for the laboratory and chemical Plant. Chichester: Wiley. 2003; p. 489.

Dejaegher B, Heyden YV. Experimental designs and their recent advances in set-up, data interpretation, and analytical applications. J Pharm Biomed Sci. 2011;56:141-158.

Leardi R. Experimental design. In: Data Handling in Science and Technology. Elsevier. 2013. p. 9-53.

Vujić Z, et al. Simultaneous analysis of irbesartan and hydrochlorothiazide: an improved HPLC method with the aid of a chemometric protocol. Molecules. 2012;17(3):3461-3474.

Jain A, et al. Application of chemometric approach for QbD-enabled development and validation of an RP-HPLC method for estimation of methotrexate. J Liq Chromatogr R T. 2019;42(15-16):502-512.

Beg S, et al. QbD-driven development and validation of an efficient bioanalytical UPLC method for estimation of olmesartan medoxomil. J Liq Chromatogr R T. 2016;39:587-597.

Habib AA, Hammad SF, Megahed SM, Kamal AH. Innovative Quality by Design Approach for Development of Green Micellar HPLC Method for Simultaneous Determination of Atorvastatin and Amlodipine. Chromatographia. 2020;83(10):1221-1231.

Vermeij TAC, Edelbroek PM. Robust isocratic high performance liquid chromatographic method for simultaneous determination of seven antiepileptic drugs including lamotrigine, oxcarbazepine and zonisamide in serum after solid-phase extraction. J Chromatogr B. 2007;857(1):40-46.

Mendia OG, et al. Efficient method development and validation for the determination of cardiovascular drugs in human plasma by SPE–UHPLC–PDA–FLD. Chromatographia. 2017;80(4):605-615.

Armstrong, N. Anthony. Pharmaceutical experimental design and interpretation. CRC Press, 2006.

Nguyet ANM, Tallieu L, Plaizier JV, Massart DL, Heyden YV. Validation of an HPLC method on short columns to assay ketoconazole and formaldehyde in shampoo. J Pharm Biomed Anal. 2003;32(1):1-19.

Van Nederkassel AM, et al. Fast separations on monolithic silica columns: method transfer, robustness and column ageing for some case studies. J Pharm Biomed Anal. 2003;32(2):233-49.

Song Q, Putcha L. Quantitation of promethazine and metabolites in urine samples using on-line solid-phase extraction and column-switching. J Chromatogr B. 2001;763(1-2):9-20.

Sun SW, Hsiu-Ting. Validated HPLC method for determination of sennosides A and B in senna tablets. J Pharm. Biomed. Anal. 2002;29(5):881-894.

Kojic-Marinkovic S, Tumbas M, Rakic T, Jancic-Stojanovic B. Plackett-Burman design in robustness testing of liquid chromatographic method for determination of sodium-valproat. Arh Farm. 2014;64(2):128–43.

Mitrović M, et al. Analytical quality by design development of an ecologically acceptable enantioselective HPLC method for timolol maleate enantiomeric purity testing on ovomucoid chiral stationary phase. J Pharm Biomed Anal. 2020;180:113034.

Abdel-Moety EM, Ezzat M, et al. A combined approach of green chemistry and Quality-by-Design for sustainable and robust analysis of two newly introduced pharmaceutical formulations treating benign prostate hyperplasia. Microcheml J. 2021;160:105711.

Beg S, et al. Applications of Monte-Carlo simulation and chemometric techniques for development of bioanalytical liquid chromatography method for estimation of rosuvastatin calcium. J Liq Chromatogr R T. 2017;40(18):907-920.

Aboushady D, Parr MK, Hanafi RS. Quality-by-Design Is a Tool for Quality Assurance in the Assessment of Enantioseparation of a Model Active Pharmaceutical Ingredient. Pharmaceuticals. 2020;13(11):364.

Nemutlu E, et al. Simultaneous multiresponse optimization of an HPLC method to separate seven cephalosporins in plasma and amniotic fluid: application to validation and quantification of cefepime, cefixime and cefoperazone. Talanta. 2009;80(1):117-126.

Dinç-zor Ş, et al. Chemometric optimization of an HPLC method for the simultaneous analysis of a multi component drug product by the help of central composite design. Microchem J. 2020;152:104322.

Quiming NS, et al. Chromatographic behavior of uric acid and methyl uric acids on a diol column in HILIC. Chromatographia. 2008;67(7):507-515.

Li P, et al. Optimizing ultraperformance liquid chromatographic analysis of 10 diterpenoid compounds in Salvia miltiorrhiza using central composite design. J Agr Food Chem. 2008;56(4):1164-1171.

Sivakumar T, et al. Multi-criteria decision making approach and experimental design as chemometric tools to optimize HPLC separation of domperidone and pantoprazole. J Pharm Biomed Anal. 2007;43(5):1842-1848.

Attimarad M, et al. Development and Validation of Rapid RP-HPLC and Green Second-Derivative UV Spectroscopic Methods for Simultaneous Quantification of Metformin and Remogliflozin in Formulation Using Experimental Design. Separations. 2020;7(4):59.

Dragomiroiu GTAB, et al. The development and validation of a rapid HPLC method for determination of piroxicam. Farmacia. 2015;63(1):123-31.

Chaudhari SR, Shirkhedkar AA. Design of experiment avenue for development and validation of RP-HPLC-PDA method for determination of apremilast in bulk and in in-house tablet formulation. J Anal Sci Tech. 2019;10(1):1-9.

Maljurić N, et al. A new strategy for development of eco-friendly RP-HPLC method using Corona Charged Aerosol Detector and its application for simultaneous analysis of risperidone and its related impurities. Microchem J. 2020;153:104394.

Czyrski A, Sznura J. The application of Box-Behnken-Design in the optimization of HPLC separation of fluoroquinolones. Sci Rep. 2019;9(1):1-10.

Jebali S, et al. Application of Factorial and Doehlert Designs for the Optimization of the Simultaneous Separation and Determination of Antimigraine Drugs in Pharmaceutical Formulations by RP-HPLC-UV. Int J Anal Chem. 2019; DOI: 10.1155/2019/9685750

Bonfilio R, et al. Multivariate optimization and validation of an analytical methodology by RP-HPLC for the determination of losartan potassium in capsules. Talanta. 2009;80:236-41.

Lafossas C, et al. Analysis of the retention of tetracyclines on reversed-phase columns: Chemometrics, design of experiments and quantitative structure-property relationship (QSPR) study for interpretation and optimization. Talanta. 2019;198:550-559.

Araujo P, Janagap S. Doehlert uniform shell designs and chromatography. J Chromatogr B. 2012;910:14-21.

Herrero A, et al. A new multiresponse optimization approach in combination with a D-Optimal experimental design for the determination of biogenic amines in fish by HPLC-FLD. Anal Chim Acta. 2016;945:31-38.

Golabchifar A, et al. Optimization of the simultaneous determination of imatinib and its major metabolite, CGP74588, in human plasma by a rapid HPLC method using D-optimal experimental design. Talanta. 2011;85(5):2320-2329.

Vanbel PF, Tilquin BL, Schoenmakers PJ. Criteria for optimizing the separation of target analytes in complex chromatograms. Chemometr Intell Lab. 1996;35(1):67-86.

Imam SS, et al. Optimization of mobile phase by 3 2-mixture design for the validation and quantification of risperidone in bulk and pharmaceutical formulations using RP-HPLC. Anal Method. 2014;6(1):282-288.

Deming SN, Morgan SL. Experimental Design: A Chemometric Approach 2nd ed. Elsevier Science; 1993: p. 436.

Saini Sumant, et al. QbD-steered development and validation of an RP-HPLC method for quantification of ferulic acid: Rational application of chemometric tools. J Chromatogr B. 2020;1155:122300. DOI: 10.1016/j.jchromb.2020.122300

Beg S, et al. Development and validation of a stability-indicating liquid chromatographic method for estimating olmesartan medoxomil using quality by design. J Chromatogr Sci. 2015;53(7):1048-1059.

ICH Harmonised Tripartite Guideline: Pharmaceutical Development Q8(R2), current Step 4 version; International Conference on Harmonisation: Geneva, 2009.

ICH Harmonised Tripartite Guideline: Quality Risk Management Q9, current Step 4 version; International Conference on Harmonisation: Geneva, 2005.

ICH Harmonised Tripartite Guideline: Pharmaceutical Quality System Q10, current Step 4 version; International Conference on Harmonisation: Geneva, 2008.

ICH Harmonised Tripartite Guideline: Development and Manufacture of Drug Substances Q11, current Step 4 version; International Conference on Harmonisation: Geneva, 2012.

Analytical Procedures and Methods Validation for Drugs and Biologics - Guidance for Industry; U.S. Food and Drug Administration Silver Spring, MD, 2015.

Otašević B, et al. Comparison of AQbD and grid point search methodology in the development of micellar HPLC method for the analysis of cilazapril and hydrochlorothiazide dosage form stability. Microchem J. 2019;145:655-663.

Tome T, et al. Development and optimization of liquid chromatography analytical methods by using AQbD principles: Overview and recent advances. Org Process Res Dev. 2019;23(9):1784-1802.

Sylvester B, et al. A Quality by Design (QbD) approach to the development of a gradient high-performance liquid chromatography for the simultaneous assay of curcuminoids and doxorubicin from long-circulating liposomes. J Pharm Biomed Anal. 2018;158:395-404.

Patel MN, Kothari CS. Multivariate approaches for simultaneous determination of avanafil and dapoxetine by UV chemometrics and HPLC-QbD in binary mixtures and pharmaceutical product. J AOAC Int. 2016;99(3):649-663.

Panda SS, et al. Analytical eco‐scale and quality by design‐oriented liquid chromatography method for simultaneous quantification of metoprolol succinate, telmisartan, and cilnidipine in their fixed‐dose combination. Sep Sci Plus. 2021;4(3):128-136.

Zhang X, Hu C. Application of quality by design concept to develop a dual gradient elution stability-indicating method for cloxacillin forced degradation studies using combined mixture-process variable models. J Chromatogr A. 2017;1514:44-53.

Székely Gy, et al. Design of experiments as a tool for LC–MS/MS method development for the trace analysis of the potentially genotoxic 4-dimethylaminopyridine impurity in glucocorticoids. J Pharm Biomed Anal. 2012;70:251-258.

Belmir H, Abbouriche A, Bennamara A, Saffaj T, Ihssane B. Using Design Space and Response Surface Methodology for developing a liquid chromatography method for simultaneous determination of five statins in pharmaceutical form. Acta Chromatogr. 2021;33:345-353.

Novotná K, Havliš J, Havel J. Optimisation of high performance liquid chromatography separation of neuroprotective peptides: fractional experimental designs combined with artificial neural networks. J Chromatogr A. 2005;1096(1-2):50-57.

Maljurić N, et al. Quantitative structure–retention relationship modeling of selected antipsychotics and their impurities in green liquid chromatography using cyclodextrin mobile phases. Anal Bioanal Chem. 2018;410(10):2533-2550.

Published
2021/08/27
Section
Review articles