Generic placeholder image

Current Drug Metabolism


ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

General Research Article

Developing a High-performance Liquid Chromatography Method for Simultaneous Determination of Loratadine and its Metabolite Desloratadine in Human Plasma

Author(s): Mahmoud M. Sebaiy* and Noha I. Ziedan

Volume 20, Issue 13, 2019

Page: [1053 - 1059] Pages: 7

DOI: 10.2174/1389200220666191125095648

Price: $65


Background: Allergic diseases are considered as the major burden on public health with increased prevalence globally. Histamine H1-receptor antagonists are the foremost commonly used drugs in the treatment of allergic disorders. The target drug in this study, loratadine, belongs to this class of drugs and its biometabolite desloratadine which is also a non-sedating H1 receptor antagonist with anti-histaminic activity being 2.5 to 4 times greater than loratadine. This study aimed to develop and validate a novel isocratic Reversed-phase High-Performance Liquid Chromatography (RP-HPLC) method for rapid and simultaneous separation and determination of loratadine and its metabolite, desloratadine in human plasma.

Methods: The drug extraction method from plasma was based on protein precipitation technique. The separation was carried out on a Thermo Scientific BDS Hypersil C18 column (5μm, 250 x 4.60 mm) in a mobile phase of MeOH: 0.025M KH2PO4 adjusted to pH 3.50 using orthophosphoric acid (85: 15, v/v) at an ambient temperature. The flow rate was maintained at 1 mL/min and maximum absorption was measured using the PDA detector at 248 nm.

Results: The retention times of loratadine and desloratadine in plasma samples were recorded to be 4.10 and 5.08 minutes, respectively, indicating a short analysis time. Limits of detection were found to be 1.80 and 1.97 ng/mL for loratadine and desloratadine, respectively, showing a high degree of sensitivity of the method. The method was then validated according to FDA guidelines for the determination of the two analytes in human plasma.

Conclusion: The results obtained indicate that the proposed method is rapid, sensitive in the nanogram range, accurate, selective, robust and reproducible compared to other reported methods.

Keywords: RP-HPLC, loratadine, desloratadine, protein precipitation, human plasma, FDA guidelines.

Graphical Abstract
Du Buske, L.M. Clinical comparison of histamine H1-receptor antagonist drugs. J. Allergy Clin. Immunol., 1996, 98, S307-S318.
Fathalla, B.; Sawsan, A.R.; Mohamed, E.A.; Sahar, Z.; Sona, B. Rapid micellar HPLC analysis of loratadine and its major metabolite desloratadine in nano-concentration range using monolithic column and fluorometric detection: application to pharmaceuticals and biological fluids. Chem. Cent. J. , 2016.10, 79..
Haria, M.; Fitton, A.; Peters, D.H. Loratadine. A reappraisal of its pharmacological properties and therapeutic use in allergic disorders. Drugs, 1994, 48, 617-637.
Kleine-Tebbe, J.; Josties, C.; Frank, G.; Stalleicken, D.; Buschauer, A.; Schunack, W.; Kunkel, G.; Czarnetzki, B. Inhibition of IgE and non-IgE mediated histamine release from human basophil leukocytes in vitro by a histamine H1-antagonist, desethoxycarbonyl-loratadine. J Allergy. Clin. Immunol., 1994, 93, 494-500.
The United States Pharmacopeia 32 The National Formulary 27, Electronic Version [CD-ROM]. US Pharmacopeial Convention,Rockville,. 2009.
Popovic, G.; Cakar, M.; Agbaba, D. Acid-base equilibria and solubility of loratadine and desloratadine in water and micellar media. J. Pharm. Biomed. Anal., 2009, 49, 42-47.
Rao, D.D.; Satyanarayana, N.V.; Malleswara, R.; Sait, S.S.; Chakole, D.; Mukkanti, K. A validated stability-indicating UPLC method for desloratadine and its impurities in pharmaceutical dosage forms. J. Pharm. Biomed. Anal., 2010, 51, 736-742.
Yang, L.; Mann, T.D.; Little, D.; Wu, N.; Clement, R.P.; Rudewicz, P.J. Evaluation of a four-channel multiplexed electrospray triple quadrupole mass spectrometer for the simultaneous validation of LC/MS/MS methods in four different preclinical matrixes. Anal. Chem., 2001, 73, 1740-1747.
Sutherland, F.C.W.; de Jager, A.D.; Badenhorst, D.; Scanes, T.; Hundt, H.K.L.; Swart, K.J.; Hundt, A.F. Sensitive liquid chromatography-tandem mass spectrometry method for the determination of loratadine and its major active metabolite descarboethoxyloratadine in human plasma. J. Chromatogr. A, 2001, 914, 37-73.
Ruperez, F.J.; Fernandez, H.; Barbas, C. LC determination of loratadine and related impurities. J. Pharm. Biomed. Anal., 2002, 29, 35-41.
Yang, L.; Amad, M.; Winnik, W.M.; Schoen, A.E.; Schweingruber, H.; Mylchreest, I.; Rudewicz, P.J. Investigation of an enhanced resolution triple quadrupole mass spectrometer for high-throughput liquid chromatography/tandem mass spectrometry assays. Rapid Commun. Mass Spectrom., 2002, 16, 2060-2066.
Naidong, W.; Addison, T.; Schneider, T.; Jiang, X.; Halls, T.D.J. A sensitive LC/MS/MS method using silica column and aqueous-organic mobile phase for the analysis of loratadine and descarboethoxy-loratadine in human plasma. J. Pharm. Biomed. Anal., 2003, 32, 609-617.
Yin, O.Q.P.; Shi, X.; Chow, M.S.S. Reliable and specific high performance liquid chromatographic method for simultaneous determination of loratadine and its metabolite in human plasma. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2003, 796, 165-172.
Qi, M.; Wang, P.; Geng, Y. Determination of desloratadine in drug substance and pharmaceutical preparations by liquid chromatography. J. Pharm. Biomed. Anal., 2005, 38, 355-359.
El-Sherbiny, D.T.; El-Enany, N.; Belal, F.F.; Hansen, S.H. Simultaneous determination of loratadine and desloratadine in pharmaceutical preparations using liquid chromatography with a microemulsion as eluent. J. Pharm. Biomed. Anal., 2007, 43, 1236-1242.
Vlase, L.; Imre, S.; Muntean, D.; Leucuta, S.E. Determination of loratadine and its active metabolite in human plasma by high-performance liquid chromatography with mass spectrometry detection. J. Pharm. Biomed. Anal., 2007, 44, 652-657.
Sora, D.I.; Udrescu, S.; David, V.; Medvedovici, A. Validated ion pair liquid chromatography/fluorescence detection method for assessing the variability of the loratadine metabolism occurring in bioequivalence studies. Biomed. Chromatogr., 2007, 21, 1023-1029.
Srinubabu, G.; Patel, R.S.; Shedbalkar, V.P.; Rao, A.A.; Rao, M.N.; Bandaru, V.V.R. Development and validation of high-throughput liquid chromatography-tandem mass spectrometric method for simultaneous quantification of loratadine and desloratadine in human plasma. J. Chromatogr. , 2007, 860, 202-208.
Patel, B.N.; Sharma, N.; Sanyal, M.; Shrivastav, P.S. LC-MS-ESI for the determination of loratadine and descarboethoxyloratadine in human plasma. J. Chromatogr. Sci., 2010, 48, 35-44.
Lu, J.; Wei, Y.C.; Markovich, R.J.; Rustum, A.M. Development and validation of a novel stability-indicating reversed-phase high-performance liquid chromatography method for assay of loratadine and determination of its related compounds. J. AOAC Int., 2010, 93, 891-903.
Ramulu, G.; Kumar, Y.R.; Vyas, K.; Suryanarayana, M.V.; Mukkanti, K. A new validated liquid chromatographic method for the determination of loratadine and its impurities. Sci. Pharm., 2011, 79, 277-292.
Youssef, R.M.; Khamis, E.F.; El-Sayed, M.A.; Abdel Moneim, M.M. Validated HPTLC method for simultaneous determination of loratadine and desloratadine in presence of coformulated drug. J. Planar Chromatogr. Mod. TLC, 2012, 25, 456-462.
Issa, N. MLynarova, M. Analysis of tablets containing the antihistamine loratadine: a contribution to the identification of impurities. Ceska Slov. Farm., 2004, 53, 192-196.
Johnson, R.; Christensen, J.; Lin, C.C. Sensitive gas-liquid chromatographic method for the determination of loratadine and its major active metabolite, descarboethoxyloratadine, in human plasma using a nitrogen-phosphorus detector. J. Chromatogr. B Biomed. Sci. Appl., 1994, 657, 125-131.
Rele, R.V.; Gurav, P.J. A simple extractive spectrophotometric determination of loratadine, desloratadine and rupatadine from pharmaceutical formulations. Int. J. Pharma Bio Sci., 2012, 3, 89.
El-Awady, M.; Belal, F.; Pyell, U. Robust analysis of the hydrophobic basic analytes loratadine and desloratadine in pharmaceutical preparations and biological fluids by sweeping-cyclodextrin-modified micellar electrokinetic chromatography. J. Chromatogr. A, 2013, 1309, 64-75.
Center for Drug Evaluation and Research. Food and Drug Administration:Rockville, 1994.Available at:. (
US Food and Drug Administration. Guidance for Industry: Bioanalytical Method Validation. Food and Drug Administration: Rockville,. 2001.
Zimmer, D. New US FDA draft guidance on bioanalytical method validation versus current FDA and EMA Guidelines: Chromatographic methods and ISR. Bioanal., 2014, 6(1), 13-19.
30. Hilbert, J.; Radwanski, E.; Affrime, M.; Perentesis, G.; Symchowicz, S.; Zam-Paglione, N. Excretion of loratadine in human breast milk. J. Clin. Pharmacol., 1988, 28(3), 234-239.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy