Desorption Electrospray Ionization Mass Spectrometry for High-Throughput Analysis of Pharmaceutical Samples in the Ambient Environment

TLDR

Desorption electrospray ionization (DESI) enables on‑line, high‑throughput monitoring of pharmaceutical samples in ambient conditions without prior preparation. The study applies positive and negative ion DESI to characterize active ingredients in tablets, ointments, and liquids while evaluating and optimizing key operating parameters such as high voltage, capillary temperature, solvent flow, and composition. The method incorporates reactive DESI with reagent‑added solvent sprays to generate stable ions, optimizes these parameters, and uses a variable‑speed moving belt for rapid qualitative and semiquantitative sampling of tablet constituents. The approach detects a wide range of compounds, achieves sampling rates up to 3 samples/s, yields 2–8 % RSD for major ions, and identifies impurities as low as ~0.1 % while minimizing carryover.

Abstract

Desorption electrospray ionization (DESI) allows mass spectrometry to be used for on-line high-throughput monitoring of pharmaceutical samples in the ambient environment, without prior sample preparation. Positive and negative ion DESI are used to characterize the active ingredients in pharmaceutical samples formulated as tablets, ointments, and liquids. Compounds of a wide variety of chemical types are detected in these complex matrices. The effects on analytical performance of operating parameters, including the electrospray high voltage, heated capillary temperature, solvent infusion rate, and solvent composition, are evaluated and optimized. In addition to experiments in which a simple solvent is sprayed onto the solid analyte samples, reactive desorption is performed by adding reagents to the solvent spray to generate particularly stable or characteristic ions with the analytes of interest. A variable-speed moving belt was built for high-throughput sampling and used to provide rapid qualitative and semiquantitative information on drug constituents in tablets. Sampling rates as high as 3 samples/s are achieved in the ambient environment. Relative standard deviations of the relative ion abundances for major components in the mass spectra are in the range of 2−8%. Impurities and components present at levels as low as ∼0.1% are identified and carryover effects are minimized in high-throughput on-line analysis of pharmaceutical samples.