A sensitive and high-throughput LC-ESI-MS/MS method to detect budesonide in human plasma: application to an evaluation of pharmacokinetics of budesonide intranasal formulations with and without charcoal-block in healthy volunteers

Abstract

Budesonide is one of the intranasal corticosteroids, referred as first-line therapy for allergic rhinitis. Its determination is a challenging task due to its extremely low plasma levels, which limits the progress in the investigation of pharmacokinetics and quality control of preparations. In this study, a sensitive and high-throughput method to determine budesonide in human plasma using budesonide-d8 as the internal standard was developed and validated. A small volume of plasma sample (0.2 mL) was diluted with 0.2 mL water, followed by a solid-phase extraction using Cleanert PEP-2 products. Extracted samples were analyzed by liquid chromatography coupled to electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Chromatographic separation of analytes was performed on an InertSustain AQ-C18 HP column (3 µm, 2.1 × 50 mm) under the reversed-phase condition with gradient elution. With the assay, linear calibration curves were obtained over the concentration range of 10–1200 pg/mL for budesonide, with considerable extraction recoveries (84.7–89.4%), and negligible matrix effects (<4.1). Moreover, the newly developed method was successfully applied to the evaluation of pharmacokinetics of two budesonide intranasal formulations with and without charcoal block in healthy volunteers.

Keywords:

• Budesonide
• nasal spray
• LC-ESI-MS/MS
• activated charcoal
• local absorption
• pharmacokinetics

Acknowledgments

The authors sincerely thank all the volunteers for participating in this clinical study.

Author contributions

All the authors contributed to the whole procedure of the current work, and agree to be responsible for all the aspects of the work.

Disclosure statement

All the authors declare no conflicts of interest.

Additional information

Funding

This study was supported by the Natural Science Foundation of Hunan Province, China [No. 2020JJ9019].