Exploring MALDI-MS as an alternative to LC-MS for the ionization and quantitation of small molecule pharmaceuticals
To advance the biological use of lipid-based drug delivery systems, sensitive qualitative and quantitative methods are needed. Mass spectrometry (MS) is ideally suited for such task with electrospray ionization (ESI) being the most widely used MS ionization method for small organic compounds, particularly quantitative workflow. Matrix Assisted Laser Desorption Ionization (MALDI) can be used as an alternative ionization technique for both qualitative and quantitative applications. We have developed six different MS-based quantification methods (within tissue culture lysate). Our data suggest that HPLC-ESI-MS/MS, perceived as the "gold standard" for quantitative workflow, was inferior to other MS-based methods, including MALDI-MS. In fact, MALDI-MS provided a simple and fast approach that could analyze the drug carrier and the encapsulated antineoplastic drug simultaneously. Unexpectedly, the antineoplastic drug formed a surprising positively charged [M-H]+ ion during MALDI-MS analysis . In contrast, the expected [M+H]+ were observed when using ESI. Understanding the mechanism which led to variations between the two ionization methods is necessary to develop qualitative/quantitative MS-based methods. We are investigating various factors that contributed to the formation of the unique [M-H]+ ion during MALDI-MS.
Despite its promise, a key limitation for MALDI-MS for the analysis of small organic compounds is background noise, primarily due to the use of a matrix. To address this issue, we are designing new structurally- modified nanoparticle MALDI matrices. Our preliminary results indicate that our newly-designed nanoparticles are superior to conventional matrices when analyzing low molecular weight pharmaceuticals.