Coated Blade Spray with a Barrier: Improving Negative Electrospray Ionization and Sample Preparation

Area of Science:

• Analytical Chemistry
• Mass Spectrometry
• Forensic Science

Background:

• Traditional substrate-based electrospray ionization (ESI) methods struggle with unstable spray, high noise, and corona discharge in negative ionization mode, particularly for complex biological matrices like blood and urine.
• Coated blade spray coupled with mass spectrometry (CBS-MS) offers an alternative, combining solid-phase microextraction (SPME) efficiency with ambient MS speed for rapid analyte screening.

Purpose of the Study:

• To develop and validate a new coated blade spray (CBS) device with a barrier feature to enhance electrospray ionization (ESI) stability and performance in negative ionization mode.
• To assess the reproducibility and accuracy of the new CBS design for the analysis of drugs of abuse in complex biological samples, specifically urine and plasma.

Main Methods:

• Development of a modified CBS blade incorporating a barrier at the ESI tip to mitigate instability issues.
• Investigation of ESI stability using microscopic observation and CBS-MS testing.
• Application of the new CBS device for the quantitative analysis of drugs of abuse in urine (negative mode) and plasma (positive mode) without internal standards.

Main Results:

• The addition of a barrier to the CBS blade reduced the total relative standard deviation (RSD%) to below 10% for sample preparation, ionization, and MS detection of drugs in negative mode.
• Analysis of drugs in urine yielded high calibration curve correlation coefficients (R² ≥ 0.9997) and an overall peak area RSD% of 6.9% for one compound across 42 samples.
• On-blade sampling of 14 drugs in plasma (positive mode) showed R² ≥ 0.9883 and limits of quantification (LOQs) ranging from 0.25 to 25 ng/mL.

Conclusions:

• The novel CBS blade design with a barrier significantly enhances ESI stability and reproducibility, particularly in negative ionization mode, for analyzing drugs in complex biological matrices.
• The method demonstrates excellent quantitative performance without the need for internal standards, highlighting its potential for high-throughput screening and automation.
• The findings offer valuable insights for optimizing CBS device design and automating protocols for ambient mass spectrometry applications.