• citations in SCIndeks: 0
  • citations in CrossRef:[1]
  • citations in Google Scholar:[]
  • visits in previous 30 days:23
  • full-text downloads in 30 days:15


article: 1 from 1  
Back back to result list
2021, vol. 71, iss. 4, pp. 279-301
Experimental design in HPLC separation of pharmaceuticals
University of Belgrade, Faculty of Pharmacy, Department of Pharmaceutical Chemistry and Drug Analysis, Serbia

Keywords: design of experiments; drug analysis; high pressure liquid chromatography; analytical method development and validation
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.
*** (2005) ICH Harmonised Tripartite Guideline: Quality Risk Management Q9. Geneva, Current Step 4 Version
*** (2009) ICH Harmonised Tripartite Guideline: Pharmaceutical Development Q8(R2). in: International Conference on Harmonisation, Geneva, Current Step 4 Version
*** (2008) ICH Harmonised Tripartite Guideline: Pharmaceutical Quality System Q10. in: International Conference on Harmonisation, Geneva, Current Step 4 Version
*** (2012) ICH Harmonised Tripartite Guideline: Development and Manufacture of Drug Substances Q11. in: International Conference on Harmonisation, Geneva, Current Step 4 Version
*** (2015) Analytical Procedures and Methods Validation for Drugs and Biologics: Guidance for Industry. Silver Spring, MD: U.S. Food and Drug Administration
Abdel-Moety, E.M., Ezzat, M., et al. (2021) 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, 160: 105711
Aboushady, D., Parr, M.K., Hanafi, R.S. (2020) Quality-by-Design Is a Tool for Quality Assurance in the Assessment of Enantioseparation of a Model Active Pharmaceutical Ingredient. Pharmaceuticals, 13(11): 364
Ahuja, S. (2011) Overview of Modern Pharmaceutical Analysis. Sep. Sci. Technol, 10: 1-9
Araujo, P., Janagap, S. (2012) Doehlert Uniform Shell Designs and Chromatography. J Chromatogr B, 910: 14-21
Armstrong, N. (2006) Pharmaceutical Experimental Design and Interpretation. CRC Press
Attimarad, M., et al. (2020) Validation of Rapid RP-HPLC Method for Concurrent Quantification of Amlodipine and Celecoxib in Pure and Formulation Using an Experimental Design. Microchem J, 152: 104365
Attimarad, M., et al. (2020) 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, 7(4): 59
Baczek, T. (2008) Computer-Assisted Optimization of Liquid Chromatography Separations of Drugs and Related Substances. Curr Pharm Anal, 4(3): 151-161
Beg, S., et al. (2017) 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, 40(18): 907-920
Beg, S., et al. (2015) Development and Validation of a Stability-Indicating Liquid Chromatographic Method for Estimating Olmesartan Medoxomil Using Quality by Design. J Chromatogr Sci, 53(7): 1048-1059
Beg, S., et al. (2016) QbD-driven Development and Validation of an Efficient Bioanalytical UPLC Method for Estimation of Olmesartan Medoxomil. J Liq Chromatogr R T, 39(13): 587-597
Belmir, H., Abourriche, A., Bennamara, A., Saffaj, T., Ihssane, B. (2021) Using Design Space and Response Surface Methodology for Developing a Liquid Chromatography Method for Simultaneous Determination of Five Statins in Pharmaceutical Form. Acta Chromatogr, 33(4): 345-353
Bezerra, M.A., et al. (2008) Response Surface Methodology (RSM) As a Tool for Optimization in Analytical Chemistry. Talanta, 76(5): 965-977
Bonfilio, R., et al. (2009) Multivariate Optimization and Validation of an Analytical Methodology by RP-HPLC for the Determination of Losartan Potassium in Capsules. Talanta, 80: 236-241
Brereton, R.G. (2003) Chemometrics-data Analysis for the Laboratory and Chemical Plant. Chichester: Wiley, 489-489
Chaudhari, S.R., Shirkhedkar, A.A. (2019) 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, 10(1): 1-9
Czyrski, A., Sznura, J. (2019) The Application of Box-Behnken-Design in the Optimization of HPLC Separation of Fluoroquinolones. Sci Rep, 9(1): 1-10
Dalvi, A.V., et al. (2018) 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, 1102: 74-82
Debrus, B., et al. (2011) Application of New Methodologies Based on Design of Experiments, Independent Component Analysis and Design Space for Robust Optimization in Liquid Chromatography. Anal Chim Acta, 691(1-2): 33-42
Dejaegher, B., Vander, H.Y. (2011) Experimental Designs and Their Recent Advances in Set-up, Data Interpretation, and Analytical Applications. J Pharm Biomed Sci, 56: 141-158
Dejaegher, B., Heyden, Y.V. (2007) Ruggedness and Robustness Testing. J Chromatogr A, 1158(1-2): 138-157
Deming, S.N., Morgan, S.L. (1993) Experimental Design: A Chemometric Approach. Elsevier Science, 2nd ed, 436
Dinç-Zor, Ş., et al. (2020) 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, 152: 104322
Dragomiroiu, G., et al. (2015) The Development and Validation of a Rapid HPLC Method for Determination of Piroxicam. Farmacia, 63(1): 123-131
Ferreira, S.L.C., et al. (2007) Statistical Designs and Response Surface Techniques for the Optimization of Chromatographic Systems. J Chromatogr A, 1158(1-2): 2-14
Ganorkar, S.B., Shirkhedkar, A.A. (2017) Design of Experiments in Liquid Chromatography (HPLC) Analysis of Pharmaceuticals: Analytics, Applications, Implications and Future Prospects. Rev Anal Chem, 36(3): 1-43
Golabchifar, A., et al. (2011) 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, 85(5): 2320-2329
Gy, S., et al. (2012) 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, 70: 251-258
Habib, A.A., Hammad, S.F., Megahed, S.M., Kamal, A.H. (2020) Innovative Quality by Design Approach for Development of Green Micellar HPLC Method for Simultaneous Determination of Atorvastatin and Amlodipine. Chromatographia, 83(10): 1221-1231
Hadjmohammadi, M.R., Ebrahimi, P. (2004) Optimization of the Separation of Anticonvulsant Agents in Mixed Micellar Liquid Chromatography by Experimental Design and Regression Models. Anal Chim Acta, 516(1-2): 141-148
Herrero, A., et al. (2016) 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, 945: 31-38
Heyden, V.Y., et al. (2001) Guidance for Robustness/ruggedness Tests in Method Validation. J Pharm Biomed Sci, 24: 723-753
Hibbert, D.B. (2012) Experimental Design in Chromatography: A Tutorial Review. J Chromatogr B, 910: 2-13
Imam, S.S., et al. (2014) Optimization of Mobile Phase by 32-mixture Design for the Validation and Quantification of Risperidone in Bulk and Pharmaceutical Formulations Using RP-HPLC. Anal. Methods, 6(1): 282-288
Jain, A., et al. (2019) Application of Chemometric Approach for QbD-enabled Development and Validation of an RP-HPLC Method for Estimation of Methotrexate. J Liq Chromatogr R T, 42(15-16): 502-512
Jebali, S., et al. (2019) 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
Kojić-Marinković, S., Tumbas, M., Rakić, T., Jančić-Stojanović, B. (2014) Plackett-Burman design in robustness testing of liquid chromatographic method for determination of sodium-valproat. Arhiv za farmaciju, vol. 64, br. 2, str. 128-143
Komsta, Ł. (2018) Chemometrics in Chromatography. CRC Press
Lafossas, C., et al. (2019) 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, 198: 550-559
Leardi, R. (2009) Experimental Design in Chemistry: A Tutorial. Anal Chim Acta, 652(1-2): 161-172
Leardi, R. (2013) Experimental Design. in: Data Handling in Science and Technology, Elsevier, 9-53
Li, P., et al. (2008) Optimizing Ultraperformance Liquid Chromatographic Analysis of 10 Diterpenoid Compounds in Salvia miltiorrhiza Using Central Composite Design. J Agr Food Chem, 56(4): 1164-1171
Lobrutto, R., Patel, T. (2007) Method Validation. in: Kazakevich Y.; Lobrutto R. [ed.] HPLC for Pharmaceutical Scientists, John Wiley & Sons, Inc, 455-502, 1st ed
Maljurić, N., et al. (2020) 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, 153: 104394
Maljurić, N., et al. (2018) Quantitative Structure-retention Relationship Modeling of Selected Antipsychotics and Their Impurities in Green Liquid Chromatography Using Cyclodextrin Mobile Phases. Anal Bioanal Chem, 410(10): 2533-2550
Mattrey, F.T., et al. (2017) Current Challenges and Future Prospects in Chromatographic Method Development for Pharmaceutical Research. TrAC Trends in Analytical Chemistry, 95: 36-46
Mendia, O.G., et al. (2017) Efficient Method Development and Validation for the Determination of Cardiovascular Drugs in Human Plasma by SPE-UHPLC-PDA-FLD. Chromatographia, 80(4): 605-615
Mitrović, M., et al. (2020) 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, 180: 113034
Nemutlu, E., et al. (2009) 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, 80(1): 117-126
Nguyet, A.N.M., Tallieu, L., Plaizier, J.V., Massart, D.L., Heyden, Y.V. (2003) Validation of an HPLC Method on Short Columns to Assay Ketoconazole and Formaldehyde in Shampoo. J Pharm Biomed Anal, 32(1): 1-19
Novotná, K., Havliš, J., Havel, J. (2005) Optimisation of High Performance Liquid Chromatography Separation of Neuroprotective Peptides: Fractional Experimental Designs Combined with Artificial Neural Networks. J Chromatogr A, 1096(1-2): 50-57
Otašević, B., et al. (2019) 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, 145: 655-663
Panda, S.S., et al. (2021) 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, 4(3): 128-136
Panda, S.S., et al. (2020) Analytical Procedure Development: Concept to Application for Chemometry Based Ultrafast LC Estimation of Pimavanserin in Pharmaceuticals. J Liq Chromatogr R T, 43(3-4): 118-130
Patel, M.N., Kothari, C.S. (2016) Multivariate Approaches for Simultaneous Determination of Avanafil and Dapoxetine by UV Chemometrics and HPLC-QbD in Binary Mixtures and Pharmaceutical Product. J AOAC Int, 99(3): 649-663
Quiming, N.S., et al. (2008) Chromatographic Behavior of Uric Acid and Methyl Uric Acids on a Diol Column in HILIC. Chromatographia, 67(7-8): 507-515
Sahu, P.K., et al. (2018) An Overview of Experimental Designs in HPLC Method Development and Validation. J. Pharm. Biomed. Anal, 147: 590-611
Saini, S., et al. (2020) QbD-steered Development and Validation of an RP-HPLC Method for Quantification of Ferulic Acid: Rational Application of Chemometric Tools. J Chromatogr B, 1155: 122300
Sivakumar, T., et al. (2007) Multi-criteria Decision Making Approach and Experimental Design as Chemometric Tools to Optimize HPLC Separation of Domperidone and Pantoprazole. J Pharm Biomed Anal, 43(5): 1842-1848
Song, Q., Putcha, L. (2001) Quantitation of Promethazine and Metabolites in Urine Samples Using On-line Solid-phase Extraction and Column-switching. J Chromatogr B, 763(1-2): 9-20
Stojanović, B. (2013) Factorial-based Designs in Liquid Chromatography. Chromatographia, 76(5-6): 227-240
Sun, S., Su, H. (2002) Validated HPLC Method for Determination of Sennosides A and B in Senna Tablets. J Pharm. Biomed. Anal, 29(5): 881-894
Sylvester, B., et al. (2018) 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, 158: 395-404
Tome, T., et al. (2019) Development and Optimization of Liquid Chromatography Analytical Methods by Using AQbD Principles: Overview and Recent Advances. Org Process Res Dev, 23(9): 1784-1802
van Nederkassel, A.M., Aerts, A., Dierick, A., Massart, D.L., Vander, H.Y. (2003) Fast Separations on Monolithic Silica Columns: Method Transfer, Robustness and Column Ageing for Some Case Studies. J Pharm Biomed Anal, 32(2): 233-249
Vanbel, P.F., Tilquin, B.L., Schoenmakers, P.J. (1996) Criteria for Optimizing the Separation of Target Analytes in Complex Chromatograms. Chemometr Intell Lab, 35(1): 67-86
Vemić, A., et al. (2013) Chaotropic Agents in Liquid Chromatographic Method Development for the Simultaneous Analysis of Levodopa, Carbidopa, Entacapone and Their Impurities. J Pharm Biomed Anal, 77: 9-15
Vermeij, T., Edelbroek, P.M. (2007) 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, 857(1): 40-46
Vogt, F.G., Kord, A.S. (2011) Development of Quality-By-Design Analytical Methods. J Pharm Sci, 100(3): 797-812
Vujić, Z., et al. (2012) Simultaneous Analysis of Irbesartan and Hydrochlorothiazide: An Improved HPLC Method with the Aid of a Chemometric Protocol. Molecules, 17(3): 3461-3474
Watson, D. (2020) Pharmaceutical Analysis 5th Ed: A Textbook for Pharmacy Students and Pharmaceutical Chemists. Edinburgh: Churchill Livingstone, 480
Yabré, M., et al. (2020) Development of a Green HPLC Method for the Analysis of Artesunate and Amodiaquine Impurities Using Quality by Design. J Pharm Biomed Anal, 190: 113507
Zhang, X., Hu, C. (2017) 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, 1514: 44-53


article language: English
document type: Review Paper
DOI: 10.5937/arhfarm71-32480
published in SCIndeks: 03/09/2021
peer review method: single-blind
Creative Commons License 4.0

Related records

No related records