title: LC-ESI-MS/MS estimation of loratadine-loaded self-nanoemulsifying drug delivery systems in rat plasma: Pharmacokinetic evaluation and computer simulations by GastroPlus™.
abstract: A rapid, sensitive, and accurate bioanalytical method was established for the quantitation and pharmacokinetic investigation of loratadine (LTD) in rat plasma by liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS/MS) using loratadine-d5 as internal standard (ISTD). The analyte and ISTD were extracted by solid-phase extraction and chromatographic separation was achieved on Gemini NX- Reverse Phase C18 (50 × 4.6mm; 5 μ) using mobile phase mixture of 5mM ammonium formate buffer in water (pH 3.5 ± 0.1 with formic acid), and acetonitrile (20:80 v/v), at a flow rate of 0.400 mL/min with injection volume of 10 μL. LTD and ISTD were detected at m/z 383.3 → 337.4 and 388.4 → 337.3 with retention time of 2.62 and 2.59 min, respectively. High sensitivity (1.0 ng/mL) was achieved using small volume of rat plasma (20 μL) and the method was validated over a linearity range of 1.05-405.41 ng/mL with high correlation coefficient (r = 0.9998). The extraction method displayed a mean process efficiency of 63.25 and 65.47% for LTD and ISTD, respectively. The validated method when successfully applied for quantification of LTD in rat plasma revealed enhanced bioavailability of orally administered LTD-loaded self-nanoemulsifying drug delivery system (SNEDDS) (Cmax, 466.65 ± 18.94 ng/mL and AUC0-t 633.00 ± 12.44 ng-h/mL) over LTD-suspension (Cmax, 104.75 ± 2.87 ng/mL and AUC0-t 287.00 ± 9.11 ng-h/mL). The in vivo-in silico prediction by the GastroPlus™ software showed good prediction accuracy for LTD-SNEDDS (fold error < 2). The Loo-Reigelman method (2-compartment) presented best model-fitting indicating adequate in vitro-in vivo correlations. Conclusively, the developed sensitive analytical method displayed enhanced systemic availability of LTD-SNEDDS, and the in vivo in silico approach revealed sufficiently good GI simulation.
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, Jharkhand, India.
authors.forename: Samridhi
authors.initials: S
authors.lastname: Verma
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, Jharkhand, India. Electronic address: dr.sandeep_pharmaceutics@yahoo.com.
authors.forename: Sandeep Kumar
authors.initials: SK
authors.lastname: Singh
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D003198:Computer Simulation; D016503:Drug Delivery Systems; D004655:Emulsions; D039563:Histamine H1 Antagonists, Non-Sedating / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D017336:Loratadine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D004655:Emulsions; D039563:Histamine H1 Antagonists, Non-Sedating; D017336:Loratadine
keywords: GastroPlus™ simulation; In vitro–in vivo correlation; LC–MS/MS validation; Loratadine-SNEDDS; Pharmacokinetics