DEVELOPMENT OF LC-MS/MS METHOD FOR DETERMINATION OF ILOPERIDONE IN RABBIT PLASMA: APPLICATION TO A PHARMACOKINETIC STUDY
Keywords:
Iloperidone, LC-MSMS, Rabbit plasma, Pharmacokinetic, Long acting formulationAbstract
Objectives: Estimation of drug in plasma during in vivo studies requires a highly sensitive and precise method. Thus, the objective of the current study is to develop a LC-MS/MS method for quantitation of Iloperidone (ILO) in rabbit plasma, which was further used for in vivo study as a part of development of long acting depot formulation.
Methods: The quantitation of the drug was determined by positive ion mode with multiple reaction monitoring (MRM). Plasma extraction was carried out using Celerity Deluxe cartridge showing more than 95 % recovery. The chromatographic conditions for quantitation of ILO were use of Kromasil C18 (50*4.6 mm, 5 µm) column using, 0.01M Ammonium format Buffer (pH 5.5): Acetonitrile (10:90) as mobile phase. Olanzapine was used as an internal standard. The developed method was applied for pharmacokinetics study of ILO in rabbits after intramuscular administration of 6.24 mg/kg dose.
Results: The method was linear over concentration range of 0.5-100 ng/ml with correlation coefficient more than 0.999. The lower limit of quantitation was 0.5 ng/ml and recovery was found more than 95% for ILO and olanzapine. Extraction and estimation of ILO were performed using the developed method. Steady release of ILO from depot formulation was observed up to 14 days in rabbits.
Conclusion: The developed LC-MS/MS method was precise and having detectability for lower drug concentration in rabbit plasma and it was successfully applied to study in vivo drug release in rabbits.
Â
Downloads
References
Mandpe L, Kyadarkunte A, Pokharkar V. High-performance liquid chromatographic method for simultaneous determination of iloperidone and idebenone in spiked plasma. Int J Chem Anal Sci 2013;4(1):19–23.
United State Pharmacopoeia, Monograph-Small Molecules Activities (Drug Substances). 2014. Available from: http: //www.usp.org/sites/default/files/usp_pdf/EN/USPNF/small_molecules_activities_-_drug_substances.pdf.
Indian Pharmacopoeia. Ghaziabad: Indian Pharmacopoeial Commission, Govt. of India-Ministry of Health and Family Welfare; 2014. p. 1948.
Assessment Report: EMA/177796/2013. London: European Medicines Agency; 2012.
Chhalotiya UK, Bhat KK, Shah DA, Patel JR. Liquid chromatographic method for the quantification of antipsychotic agent iloperidone in pharmaceutical formulation. ISRN Anal Chem 2012;1-6.
Markus A, Rolf L. Depot formulation of iloperidone with a polymer. European patent. EP2295058A1; 2011.
Wieckhusen D, Glausch A, Ahlheim M. Injectable depot formulation comprising crystals of iloperidone. United States patent. US 20050250813 A1; 2005.
Sainati SM, Hubbard JW, Chi E, Grasing K, Brecher MB. Safety, tolerability, and effect of food on the pharmacokinetics of iloperidone (HP 873), a potential atypical antipsychotic. J Clin Pharamcol 1995;35(7):713–20.
Mutlib AE, Strupczewski JT. Picogram determination of iloperidone in human plasma by solid-phase extraction and by high-performance liquid chromatography-selected-ion monitoring electrospray mass spectrometry. J Chromatogr B Biomed Appl 1995;669(2):237–46.
Jia M, Li J, He X, Liu M, Zhou Y, Fan Y. Simultaneous determination of iloperidone and its two active metabolites in human plasma by liquid chromatography–tandem mass spectrometry: Application to a pharmacokinetic study. J Chromatogr B 2013;928:52–7.
Hayes RN. Bioanalytical methods for sample cleanup: preparation of biological samples for chromatographic analyses. Bio Pharm Int 2012;25(12):52–4.
Sethi PD. editor. High performance liquid chromatography-Quantitative analysis of pharmaceutical formulation. 1st ed. Mumbai: CBS publishers and distributors; 2001.
FDA: CDER, Guidance for industry bioanalytical method validation. 2013. Available from: www.fda.gov/downloads/Drugs/Guidances/ucm070107.pdf.