1. bookVolume 58 (2008): Issue 3 (September 2008)
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28 Feb 2007
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access type Open Access

Use of chemometrics for development and validation of an RP-HPLC method for simultaneous determination of haloperidol and related compounds

Published Online: 22 Dec 2008
Page range: 243 - 256
Journal Details
License
Format
Journal
First Published
28 Feb 2007
Publication timeframe
4 times per year
Languages
English

A rapid resolution reversed-phase high performance liquid chromatographic (RR RP-HPLC) method has been developed and validated for simultaneous determination of haloperidol and six related compounds. Investigated matrix was a laboratory mixture of a therapeutic active substance haloperidol and its six related compounds in concentration ratio 300:1. Experimental design was used during method optimization (full factorial 23 design) and robustness testing (Central Composite Circumscribed design). Three factors: organic phase variation during gradient elution, flow rate and gradient rise time were independent variables. To estimate the system response during the optimization procedure and robustness testing, resolution (Rs) and a chromatographic response function (CRF) were used. Chromatography was performed with the mobile phase containing phosphate buffer pH 6.5 and acetonitrile as organic modifier. Separation was achieved using gradient elution (organic phase fraction changed linearly from 20 to 72 %) over 7 min. A Zorbax Eclipse XDB C18 Rapid Resolution HT 4.6 mm x 50 mm, 1.8 μm particle size, column was used at 25 °C at a flow rate of 1.5 mL min-1. UV detection was performed at 230 nm. The total time for chromatographic separation was 5.5 min with a total analysis time of 7.0 min. The method was validated for its linearity, precision, modal recovery and robustness.

Keywords

E. Mutschler, H. Derendorf, M. Schhäfer-Korting, K. Elord and K. S. Estes, in Drug Actions, Basic Principles and Therapeutic Aspects, Medpharm Scientific Publishers, Stuttgart 1995, pp. 116-125.Search in Google Scholar

T. Arinobu, H. Hattori, M. Iwai, A. Ishii, T. Kumazawa, O. Suzuki and H. Seno, Liquid chromatographic-mass spectrometric determination of haloperidol and its metabolites in human plasma and urine, J. Chromatogr.B 776 (2002) 107-113; DOI:10.1016/S1570-0232(02)00175-7.Search in Google Scholar

G. Theodoridis, M. A. Lontou, F. Michopoulos, M. Sucha and T. Gondova, Study of multiple solid-phase micro extraction combined off-line with high performance liquid chromatography. Application in the analysis of pharmaceuticals in urine, Anal. Chim. Acta 516 (2004) 197-204; DOI: 10.1016/j.aca.2004.04.012.Search in Google Scholar

S. Ouanes, M. Kallel, H. Trabels, F. Safta and K. Bouzouita, Zero-crossing derivative spectro-photometry for the determination of haloperidol in presence of parabens, J. Pharm. Biomed. Anal. 17 (1998) 361-364; DOI: 10.1016/S0731-7085(97)00174-X.Search in Google Scholar

H. S. El-Desoky and M. M. Ghoneim, Assay of the anti-psychotic drug haloperidol in bulk form, pharmaceutical formulation and biological fluids using square-wave adsorptive stripping voltammetry at a mercury electrode, J. Pharm. Biomed. Anal. 38 (2005) 543-550; DOI: 10.1016/j.jpba.2005.01.017.Search in Google Scholar

P. Cutroneo, M. Beljean, R. Phan Tan Luuc and A.-M. Siouffi, Optimization of the separation of some psychotropic drugs and their respective metabolites by liquid chromatography, J. Pharm. Biomed. Anal. 41 (2006) 333-340; DOI: 10.1016/j.jpba.2005.10.050.Search in Google Scholar

R. Driouichl, H. Trabelsi and K. A. Bouzouita, Stability-indicating assay for haloperidol syrup by high-performance liquid chromatography, Chromatographia 53 (2001) 629-634; DOI: 10.1007/ BF02493010.Search in Google Scholar

H. Trabelsi, S. Bouabdallah, K. Bouzouita and F. Safta, Determination and degradation study of haloperidol by high performance liquid chromatography, J. Pharm. Biomed. Anal. 29 (2002) 649-657; DOI: 10.1016/S0731-7085(02)00104-8.Search in Google Scholar

International Conference on Harmonization (ICH): Q3A (R2), Impurities in New Drug Substances, EMEA, London 2006.Search in Google Scholar

M. Franck, Impurity Profiling with the Agilent 1200 Series LC System Part 3: Rapid Condition Scouting for Method Development, Agilent Application Note, Agilent Technologies Inc., Waldbronn, 2006; Publication Number 5989-5619EN.Search in Google Scholar

M. Joseph, High-throughput HPLC with Short Columns and New Sub Two-micron Particles, Agilent Application Note, Agilent Technologies Inc., New York, 2003; Publication Number 5988-9615EN.Search in Google Scholar

T. Lundsted, E. Seifert, L. Abramo, B. Thelin, A. Nystorm, J. Pettersen and R. Bergman, Experimental design and optimization, Chemom. Intell. Lab. Syst. 42 (1998) 3-40; DOI: 10.1016/S0169-7439(98)00065-3.Search in Google Scholar

P. W. Araujo and R. G. Brereton, Experimental design II. Optimization. Trends Anal. Chem. 15 (1996) 63-68; DOI: 10.1016/0165-9936(96)80762-X.Search in Google Scholar

S. N. Deming and S. L. Morgan, Experimental Design: A Chemometric Approach, Elsevier, Amsterdam, 1993.Search in Google Scholar

D. Bylund, A. Bergens and S. P. Jacobsson, Optimization of chromatographic separations by use of a chromatographic response function, empirical modeling and multivariate analysis, Chromatographia 44 (1997) 74-80; DOI: 10.1007/BF02466519.Search in Google Scholar

International Conference on Harmonization (ICH): Q2 (R1), Validation of Analytical Procedures: Text and Methodology, EMEA, London 2005.Search in Google Scholar

H. Fabre, Robustness testing in liquid chromatography and capillary electrophoresis, J. Pharm. Biomed. Anal. 14 (1996) 1125-1132; DOI: 10.1016/s0731-7085(96)01770-0.Search in Google Scholar

G. A. Lewis, D. Mathieu and R. Phan-Tan-Luu, Pharmaceutical Experimental Design, Marcel Decker, New York 1999Search in Google Scholar

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