Rapid determination of biogenic amines in ossotide injections by microfluidic chip-mass spectrometry platform: Optimization of microfluidic chip derivatization using response surface methodology

Abstract

The microfluidic-chip mass spectrometry (MS) platform was developed for the rapid and automatic determination of 10 biogenic amines (BAs) in ossotide injections. The microfluidic chip was primarily consisted of a square unit for derivatization and a solid phase extraction (SPE) unit. The derivatization unit could achieve automatic mixing and reaction between sample and derivatization reagents, after which the targets were purified and enriched in SPE unit, further improving the sensitivity. To select the optimal derivatization conditions, four major parameters affecting derivatization in the microfluidic chip were optimized using Box-Behnken response surface design. On-chip derivatization unit enabled the shortest derivatization time by thorough solution mixing. There is no additional pretreatment required for the entire process. The developed method achieved satisfactory limits of detection (0.045–0.855 ng/mL) and limits of quantitation (0.156–3.11 ng/mL). The recoveries of the method ranged from 75.0 % to 106 % when coupled in-line with MS. This pretreatment chip-MS platform was successfully applied to BAs detection in the commercially available ossotide injections, demonstrating the prospects of this technique as a potential method for the rapid determination. The results of BAs in ossotide injections provide a basis for the formulation of the limit standard in pharmaceutical preparations.