Robust analysis of the hydrophobic basic analytes loratadine and desloratadine in pharmaceutical preparations and biological fluids by sweeping—cyclodextrin-modified micellar electrokinetic chromatography

• A new CD-MEKC method for the determination of LOR and DSL is developed.
• Capillary wall adsorption problem of hydrophobic basic analytes is minimized.
• Full validation study is performed using the ICH guidelines.
• Application to tablets, spiked human urine and impurity testing is successfully done.
• Method development strategy can be extended to other hydrophobic basic analytes.

The analysis of hydrophobic basic analytes by micellar electrokinetic chromatography (MEKC) is usually challenging because of the tendency of these analytes to be adsorbed onto the inner capillary wall in addition to the difficulty to separate these compounds as they exhibit extremely high retention factors. A robust and reliable method for the simultaneous determination of loratadine (LOR) and its major metabolite desloratadine (DSL) is developed based on cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) with acidic sample matrix and basic background electrolyte (BGE). The influence of the sample matrix on the reachable focusing efficiency is studied. It is shown that the application of a low pH sample solution mitigates problems associated with the low solubility of the hydrophobic basic analytes in aqueous solution while having advantages with regard to on-line focusing. Moreover, the use of a basic BGE reduces the adsorption of these analytes in the separation compartment. The separation of the studied analytes is achieved in less than 7 min using a BGE consisting of 10 mmol L−1 disodium tetraborate buffer, pH 9.30 containing 40 mmol L−1 SDS and 20 mmol L−1 hydroxypropyl-β-CD while the sample solution is composed of 10 mmol L−1 phosphoric acid, pH 2.15. A full validation study of the developed method based on the pharmacopeial guidelines is performed. The method is successfully applied to the analysis of the studied drugs in tablets without interference of tablet additives as well as the analysis of spiked human urine without any sample pretreatment. Furthermore, DSL can be detected as an impurity in LOR bulk powder at the stated pharmacopeial limit (0.1%, w/w). The selectivity of the developed method allows the analysis of LOR and DSL in combination with the co-formulated drug pseudoephedrine. It is shown that in CD-MEKC with basic BGE, solute–wall interactions are effectively suppressed allowing the development of efficient and precise methods for the determination of hydrophobic basic analytes, whereas the use of a low pH sample solution has a positive impact on the attainable sweeping efficiency without compromising peak shape and resolution.