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

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.