Quantification of desloratadine in human plasma by LC-ESI-MS/MS and application to a pharmacokinetic study

A simple, sensitive, and specific liquid chromatography tandem mass spectrometry (LC-MS/ MS) method was developed for the quantification of desloratadine (DL) in human plasma using desloratadine-d5 (DLD5) as an internal standard (IS). Chromatographic separation was performed using an Xbridge C18 column (50 mm 4.6 mm, 5 mm) with an isocratic mobile phase composed of 10 mM ammonium formate: methanol (20:80, v/v), at a flow rate of 0.7 mL/min. DL and DLD5 were detected with proton adducts at m/z 311.2-259.2 and 316.2-264.3 in multiple reaction monitoring (MRM) positive modes, respectively. Liquid–liquid extraction (LLE) method was used to extract the drug and the IS. The method was validated over a linear concentration range of 5.0–5000.0 pg/mL with a correlation coefficient of (r2)Z0.9994. This method demonstrated intra- and inter-day precision within 0.7–2.0% and 0.7–2.7%, and an accuracy within 101.4–102.4%, and 99.5–104.8%. DL was found to be stable throughout the freeze–thaw cycles, bench-top, and postoperative stability studies. This method was successfully applied in the analysis of plasma samples following oral administration of DL (5 mg) in 35 healthy Indian male human volunteers under fasting conditions.

Method Development and Validation for Simultaneous Estimation of Montelukast Sodium and Desloratadine by RP-HPLC

A novel, precise, accurate, rapid and cost effective isocratic reverse-phase high performance liquid chromatographic (RP-HPLC) method was developed, optimized and validated for the simultaneous estimation of Montelukast Sodium (MON) and Desloratadine (DES) in pharmaceutical dosage forms. The drugs were estimated using Hypersil BDS C18 (250 mm × 4.6 mm I.D., 5 μ particle size) column. The mobile phase composed of orthophosphoric acid and water in the ratio of 20:80 v/v, at a flow rate of 1.0 ml/min was used for the separation. Detection was carried out at 280 nm. The linearity range obtained was 10 - 30 μg/ml for MON and 5 - 15 μg/ml for DES with retention times of 2.929 min and 4.439 min for MON and DES respectively. The correlation coefficient values were found to be 0.999. Precision studies showed % RSD values less than 2% for both the drugs in all the selected concentrations. The percentage recoveries of MON and DES were in the range of 99.59% - 99.82% and 99.60% - 99.80% respectively. The limit of detection (LOD) and limit of quantification (LOQ) were 0.176 μg/ml, 0.587 μg/ml for MON and 0.087 μg/ml, 0.292 μg/ml for DES respectively. The method was validated as per the International Conference on Harmonization (ICH) guidelines. The proposed validated method was successfully used for the quantitative analysis of commercially available tablet dosage forms.

Effects of Desloratadine Citrate Disodium combined with Budesonide suspension on serum IgE, EOS and inflammatory factors in patients with CRS after endoscopic sinus surgery

Objective: To observe the clinical application of Desloratadine Citrate Disodium combined with Budesonide suspension in patients with chronic rhinosinusitis CRS after endoscopic sinus surgery, and analyze the change of serum immunoglobulin E (IgE), eosinophils (EOS) and inflammatory factors level in patients. Method: A total of 90 cases of patients with CRS were randomly divided into control group (n=45) and observation group (n=45) according to the lottery method. Both groups were treated with endoscopic sinus surgery. On the basis of this, control group was given Budesonide suspension and observation group was treated with Desloratadine Citrate Disodium combined with Budesonide suspension. The change of serum IgE, EOS and inflammatory factors were measured before and after operation in all subjects. Results: There was no significant difference in IgE and EOS levels between control group and observation group before treatment. After treatment, the levels of serum IgE and EOS in the two groups were significantly lower than those before treatment. Moreover, after treatment, observation group was lower than control group, and the difference was significant. There was no significant difference in inflammatory factors level between control group and observation group before treatment. After treatment, the levels of serum IL-6, IL-8, TNF-α and hs-CRP were significantly lower than those before treatment. After treatment, observation group was lower than the control group in the same period, the difference was significant. Conclusion:Combined Desloratadine Citrate Disodium treatment for CRS patients on the basis of endoscopic sinus surgery and Budesonide Nasal Spray treatment, it can more effectively reduce serum IgE and EOS levels, decrease the inflammatory response. Therefore it was a potential effective treatment for patients with CRS.

Synthesis and biological evaluation of novel derivatives of desloratadine

Series of novel derivatives of desloratadine designed as arginine vasopressin receptor antagonists were synthesized and structurally characterized by melting points,^1H NMR and HRMS.Their in vivo diuretic activities were evaluated on rats,and several target compounds showed promising diuretic results, especially compounds 8,18,27 and 31.Further in vitro bonding assay and cAMP assay showed that these compounds had a higher affinity to vasopressin V2 receptor than VI a receptor.Our studies indicated that desloratadine may be an active substructure for novel arginine vasopressin receptor antagonist development.