Highly Sensitive LC-MS/MS Method for Quantification of Beclomethasone in Human Plasma

User Benefits

- Rapid, simple and sensitive method with LLOQ of 5.0 pg/mL. - An extended Calibration Curve reduces reanalysis of samples outside range. - Quick and single step sample extraction method increased sample productivity.

Introduction

Beclomethasone dipropionate (BDP) is an inhaled corticosteroid used as maintenance treatment in the prophylaxis of asthma attacks. Beclomethasone is a 17 alpha-hydroxy steroid that is prednisolone in which the hydrogens at the 9 alpha and 16 beta positions are substituted by a chlorine and a methyl group, respectively. Formulations for oral inhalation, intranasal, and topical use are available for BDP. Compared to earlier corticosteroids such as dexamethasone and prednisolone, BDP is reported to be less irritating to the nasal mucosa with a longer duration of action when administered intranasally. BDP administered in the form of oral inhalation results in very low systemic bioavailability. This translates into significant challenges to develop a sensitive and reproducible bioanalytical method that can reliably measure plasma levels of BDP at very low expected levels. The required LLOQ for most inhalation products is typically in the range of pg/mL to sub pg/mL. Very few analytical methods have been developed to determine BDP in biological samples using HPLC with tandem mass spectrometric detection (LC–MS/MS) and the lowest reported LLOQ of 25.0 pg/mL. These methods fall short of the ideal target sensitivity required by the pharmaceutical research, and this motivated us for the current study. The main aim of this work is to develop a LC-MS/MS method at picogram level (LLOQ –5.0 pg/mL) using BDP-D10 as internal standard to support regulatory studies.

March 13, 2025 GMT