Determination of Loratadine and Its Active Metabolite in Plasma by LC/MS/MS: An Adapted Method for Children

Author(s): Qian Li, Hai-Yan Shi, Kai Wang, Min Kan, Yi Zheng, Guo-Xiang Hao, Xin-Mei Yang, Yi-Lei Yang, Le-Qun Su, Wei Zhao*

Journal Name: Current Pharmaceutical Analysis

Volume 16 , Issue 7 , 2020

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Graphical Abstract:


Abstract:

Introduction: Loratadine (LOR) (Fig. 1), an active H1 receptor antagonist, is often used in the treatment of allergic disorders such as seasonal allergies and skin rash [1]. LOR was clinically approved for symptomatic relief of nasal and non-nasal symptoms of allergic rhinitis in children ≥2years.

Materials and Methods: An adapted method of liquid chromatography-mass spectrometry (LC/MS/MS) was developed and validated to measure the concentrations of loratadine (LOR) and its active metabolite descarboethoxyloratadine (DCL) from pediatric plasma. After being mixed with the internal standard (IS, propranolol) and precipitated with methanol, samples were centrifuged and 20 μL of the supernatants were injected into the HPLC system. Separation was carried out on a reversed-phase C18 gradient column using a mobile phase consisting of water (containing 0.1 % formic acid) and acetonitrile. The flow rate was 0.5 mL/min and the running time was 5.0 min for each sample.

Results and Conclusion: Quantitation of LOR, DCL and IS was performed using MRM mode and the transitions were: 383.1 → 337.1 for LOR, 311.1 → 259.0 for DCL and 260.2 → 116.0 for propranolol, respectively. The method was validated according to FDA guidelines, precisions and accuracies met the requirements in all cases. Calibration curves were 0.2–50.0 ng/mL for both LOR and DCL. This method was then applied for a pilot study examining the pharmacokinetics and therapeutic drug monitoring of LOR in children.

Keywords: Loratadine, descarboethoxyloratadine, plasma, LC/MS/MS, children, therapeutic drug.

[1]
Clissold, S.P.; Sorkin, E.M.; Goa, K.L. Loratadine. A preliminary review of its pharmacodynamic properties and therapeutic efficacy. Drugs, 1989, 37(1), 42-57.
[http://dx.doi.org/10.2165/00003495-198937010-00003] [PMID: 2523301]
[2]
Salmun, L.M.; Herron, J.M.; Banfield, C.; Padhi, D.; Lorber, R.; Affrime, M.B. The pharmacokinetics, electrocardiographic effects, and tolerability of loratadine syrup in children aged 2 to 5 years. Clin. Ther., 2000, 22(5), 613-621.
[http://dx.doi.org/10.1016/S0149-2918(00)80048-X] [PMID: 10868558]
[3]
Geha, R.S.; Meltzer, E.O. Desloratadine: A new, nonsedating, oral antihistamine. J. Allergy Clin. Immunol., 2001, 107(4), 751-762.
[http://dx.doi.org/10.1067/mai.2001.114239] [PMID: 11295678]
[4]
Ramanathan, R.; Reyderman, L.; Kulmatycki, K.; Su, A.D.; Alvarez, N.; Chowdhury, S.K.; Alton, K.B.; Wirth, M.A.; Clement, R.P.; Statkevich, P.; Patrick, J.E. Disposition of loratadine in healthy volunteers. Xenobiotica, 2007, 37(7), 753-769.
[http://dx.doi.org/10.1080/00498250701463317] [PMID: 17620221]
[5]
Matzke, G.R.; Halstenson, C.E.; Opsahl, J.A.; Hilbert, J.; Perentesis, G.; Radwanski, E.; Zampaglione, N. Pharmacokinetics of loratadine in patients with renal insufficiency. J. Clin. Pharmacol., 1990, 30(4), 364-371.
[http://dx.doi.org/10.1002/j.1552-4604.1990.tb03607.x] [PMID: 2140371]
[6]
Radwanski, E.; Hilbert, J.; Symchowicz, S.; Zampaglione, N. Loratadine: multiple-dose pharmacokinetics. J. Clin. Pharmacol., 1987, 27(7), 530-533.
[http://dx.doi.org/10.1002/j.1552-4604.1987.tb03061.x] [PMID: 2958516]
[7]
Zhang, Y.F.; Chen, X.Y.; Zhong, D.F.; Dong, Y.M. Pharmacokinetics of loratadine and its active metabolite descarboethoxyloratadine in healthy Chinese subjects. Acta Pharmacol. Sin., 2003, 24(7), 715-718.
[PMID: 12852841]
[8]
Ghosal, A.; Gupta, S.; Ramanathan, R.; Yuan, Y.; Lu, X.; Su, A.D.; Alvarez, N.; Zbaida, S.; Chowdhury, S.K.; Alton, K.B. Metabolism of loratadine and further characterization of its in vitro metabolites. Drug Metab. Lett., 2009, 3(3), 162-170.
[http://dx.doi.org/10.2174/187231209789352067] [PMID: 19702548]
[9]
Yumibe, N.; Huie, K.; Chen, K.J.; Snow, M.; Clement, R.P.; Cayen, M.N. Identification of human liver cytochrome P450 enzymes that metabolize the nonsedating antihistamine loratadine. Formation of descarboethoxyloratadine by CYP3A4 and CYP2D6. Biochem. Pharmacol., 1996, 51(2), 165-172.
[http://dx.doi.org/10.1016/0006-2952(95)02169-8] [PMID: 8615885]
[10]
Yin, O.Q.; Shi, X.J.; Tomlinson, B.; Chow, M.S. Effect of cyp2d6*10 allele on the pharmacokinetics of loratadine in chinese subjects. Drug Metab. Dispos., 2005, 33(9), 1283-1287.
[http://dx.doi.org/10.1124/dmd.105.005025] [PMID: 15932952]
[11]
Yin, O.Q.; Shi, X.; Chow, M.S. Reliable and specific highperformance liquid chromatographic method for simultaneous determination of loratadine and its metabolite in human plasma. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2003, 796(1), 165-172.
[http://dx.doi.org/10.1016/j.jchromb.2003.08.023] [PMID: 14552827]
[12]
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. Appl., 1994, 657(1), 125-131.
[http://dx.doi.org/10.1016/0378-4347(94)80078-2] [PMID: 7952058]
[13]
Naidong, W.; Addison, T.; Schneider, T.; Jiang, X.; Halls, T.D. A sensitive LC/MS/MS method using silica column and aqueousorganic mobile phase for the analysis of loratadine and descarboethoxy-loratadine in human plasma. J. Pharm. Biomed. Anal., 2003, 32(4-5), 609-617.
[http://dx.doi.org/10.1016/S0731-7085(03)00168-7] [PMID: 12899951]
[14]
Sutherland, F.C.; de Jager, A.D.; Badenhorst, D.; Scanes, T.; Hundt, H.K.; 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(1-2), 37-43.
[http://dx.doi.org/10.1016/S0021-9673(01)00646-X] [PMID: 11358228]
[15]
Vlase, L.; Imre, S.; Muntean, D.; Leucuta, S.E. Determination of loratadine and its active metabolite in human plasma by highperformance liquid chromatography with mass spectrometry detection. J. Pharm. Biomed. Anal., 2007, 44(3), 652-657.
[http://dx.doi.org/10.1016/j.jpba.2006.08.013] [PMID: 16962733]
[16]
U.S Food & Drug Administration. Bioanalytical Method Validation Guidance for Industry., 2018.May,


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Article Details

VOLUME: 16
ISSUE: 7
Year: 2020
Published on: 17 August, 2020
Page: [909 - 915]
Pages: 7
DOI: 10.2174/1573412915666190416121233
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