Comparison of MALDI to ESI on a Triple Quadrupole Platform for Pharmacokinetic Analyses

Abstract

This present work describes the systematic experimental comparison of electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI) for pharmacokinetic (PK) analysis of two drug candidates from rat plasma using single reaction monitoring (SRM) on a triple quadrupole mass spectrometer. The electrospray assay is an established method using a fast liquid chromatography (LC) separation of the sample extracts prior to mass spectrometry analysis. The novel MALDI assays measured the concentration levels of the drug candidates directly from the spotted sample extracts. Importantly, for both LC-ESI and MALDI the same solid-phase sample extraction protocol, internal standards, triple quadrupole mass analyzer platform, and SRM conditions were used, thus effectively standardizing all experimental parameters of the two assays. Initially, analytical figures of merit such as linearity, limit of quantitation, precision, and accuracy were determined from the calibration curves, indicating very similar performance for both LC-ESI and MALDI. Moreover, the LC-ESI rat plasma concentration time profiles of the drug candidates after orally dosing the animals were accurately reproduced by the MALDI assay, giving virtually identical PK results. The direct MALDI assay, however, was able to generate the data at least 50 x faster than the LC-ESI assay. It is shown in this study that analyzing the entire PK curve for one animal took less than 2 min using MALDI (with five replicate analyses per sample), whereas the corresponding LC-ESI assay required 80 min, however, allowing only two replicate measurements in that time frame.

Biomedical application of MALDI mass spectrometry for small‐molecule analysis

“…Thus, in MALDI-MS, smaller volumes of samples can be used for analysis, smaller amounts of the samples are consumed during analysis, but higher efficiencies are obtained. Application of MALDI-triple quadrupole MS has shown that the intrinsic differences between MALDI-MS and LC-MS described above approximately cancel, and in practice therefore, the limits of quantification obtained by MALDI-MS and ESI-MS are approximately comparable (Volmer et al, 2007).…”

“…To obtain good sensitivities, the deposited matrix was re-crystallized with water vapor; this recrystallization procedure did not result in loss of spatial information. Volmer et al (2007) compared MALDI-triple quadrupole MS and LC-MS for the plasma pharmacokinetic analysis of two drug candidates that were administered to rats. Chemical analogs were used as internal standards, and plasma samples (125 mL) SMALL-MOLECULE MALDI & were prepared with SPE.…”

Impact of analyte ablation and surface acidity of Pd nanoparticles on efficiency of surface-assisted laser desorption/ionization-mass spectrometry

“…As well, silver nanoparticles were applied to a wide variety of biological molecules of different structures [7]. On the other hand, numerous SALDI materials have not shown the same universal applicability for diverse chemical structures as seen for established MALDI matrices [8][9][10] and often work only for specific compound classes.…”

Determination of the antiretroviral drug tenofovir in plasma from HIV‐infected adults by ultrafast isotope dilution MALDI‐triple quadrupole tandem mass spectrometry

“…We demonstrated previously that MALDI-QqQ-MS technology has a great usability and is a versatile tool in the determination of concentrations (extra-and intracellular) of small molecules such as antiretroviral drugs (protease inhibitors), [14,15] anticancer drugs [13] but also other types of drugs [16 -18] and as screening tool in enzyme kinetic studies. [19] In a study by Volmer et al [20] the MALDI-QqQ-MS technology demonstrated equal performances compared with LC-QqQ-MS/MS instrumentation applying electrospray ionization (ESI) as ionization source when applied in pharmacokinetic studies. Previously, Notari et al [21,22] demonstrated that MALDI-TOF could be applied for the determination of low concentrations of antiretroviral drugs in plasma samples although concentrations of the antiretroviral drugs were not determined by isotope dilution mass spectrometry but by means of internal standard quantification.…”