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

Abstract

BackgroundLoratadine 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 sample extraction steps.ResultsA highly-sensitive and time-saving micellar liquid chromatographic method is developed for the simultaneous determination of loratadine and desloratadine. The proposed method is the first analytical method for the determination 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%.ConclusionsThe 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.Graphical abstractTypical chromatogram of loratadine and its major metabolite desloratadine using the proposed micellar HPLC method

Antiallergic Treatment of Bariatric Patients: Potentially Hampered Solubility/Dissolution and Bioavailability of Loratadine, but Not Desloratadine, Post-Bariatric Surgery

“…Indeed, the loratadine log P value (5.0) is higher than that of desloratadine (3.2). 78,79 Solubility values have to be judged with respect to the drug dose; the higher the dose is, the more likely it is to have solubility/dissolution difficulties after the surgery. While majority of oral drugs have a maximal unit dosage in the range of hundred(s) milligrams/dose, 80−82 the drugs studied in this research have relatively low doses: only 10 and 5 mg for loratadine and desloratadine, respectively.…”

Pharmacokinetics and Tissue Distribution of Loratadine, Desloratadine and Their Active Metabolites in Rat based on a Newly Developed LC-MS/MS Analytical Method

“…A number of analytical methods, including HPLC-UV [5], HPLC-FLD [6], HPLC-MS/MS [7,8], turbulent flow chromatography (TFC)-MS/MS [9], and LC-MS/MS [10][11][12][13][14][15], have been established to simultaneously determine LOR and DL, DL and 3-OH-DL in biological fluids. Many of these methods require high sample volumes [5,15] and so far there has been no reported study that simultaneously quantified LOR, DL, 6-OH-DL, 5-OH-DL and 3-OH-DL in biological samples.…”

A Novel Green Micellar HPLC-UV Method for the Estimation of Vandetanib in Pure Form, Human Urine, Human Plasma and Human Liver Microsomes Matrices with Application to Metabolic Stability Evaluation

“…Additionally, VNB was estimated either alone or in combination with other drugs [10][11][12][13][14]. The micellar liquid chromatographic analytical method is one mode of eco-friendly analytical chemistry and is reported for the separation of a number of drugs [15][16][17]. Pharmacokinetic studies on VNB in humans were performed in phase I dose escalation studies [18] and in phase II trials at VNB doses of 100 and 300 mg/day [19].…”