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

Background: Loratadine is a commonly used selective non‐sedating antihistaminic drug. Desloratadine is the active metabolite of loratadine and, in addition, a potential impurity in loratadine bulk powder stated by the United States Pharmacopeia as a related substance of loratadine. Published methods for the determination of both analytes suffer from limited throughput due to the time‐consuming steps and tedious extraction procedures needed for the analysis of biological samples. Therefore, there is a strong demand to develop a simple rapid and sensitive analytical method that can detect and quantitate both analytes in pharmaceutical preparations and biological fluids without prior sam‐ ple extraction steps. Results: A highly‐sensitive and time‐saving micellar liquid chromatographic method is developed for the simultane‐ ous determination of loratadine and desloratadine. The proposed method is the first analytical method for the deter‐ mination of this mixture using a monolithic column with a mobile phase composed of 0.15 M sodium dodecyl sulfate, 10% n‐Butanol and 0.3% triethylamine in 0.02 M phosphoric acid, adjusted to pH 3.5 and pumped at a flow rate of 1.2 mL/min. The eluted analytes are monitored with fluorescence detection at 440 nm after excitation at 280 nm. The developed method is linear over the concentration range of 20.0–200.0 ng/mL for both analytes. The method detection limits are 15.0 and 13.0 ng/mL and the limits of quantification are 20.0 and 18.0 ng/mL for loratadine and desloratadine, respectively. Validation of the developed method reveals an accuracy of higher than 97% and intra‐ and inter‐day precisions with relative standard deviations not exceeding 2%. Conclusions: The method can be successfully applied to the determination of both analytes in various matrices including pharmaceutical preparations, human urine, plasma and breast milk samples with a run‐time of less than 5 min and without prior extraction procedures. The method is ideally suited for use in quality control laboratories. Moreover, it could be a simple time‐saving alternative to the official pharmacopeial method for testing desloratadine as a potential impurity in loratadine bulk powder.