High-throughput quantitative analysis by desorption electrospray ionization mass spectrometry

Abstract

A newly developed high-throughput desorption electrospray ionization (DESI) source was characterized in terms of its performance in quantitative analysis. A 96-sample array, containing pharmaceuticals in various matrices, was analyzed in a single run with a total analysis time of 3 min. These solution-phase samples were examined from a hydrophobic PTFE ink printed on glass. The quantitative accuracy, precision, and limit of detection (LOD) were characterized. Chemical background-free samples of propranolol (PRN) with PRN-d 7 as internal standard (IS) and carbamazepine (CBZ) with CBZ-d 10 as IS were examined. So were two other sample sets consisting of PRN/PRN-d 7 at varying concentration in a biological milieu of 10% urine or porcine brain total lipid extract, total lipid concentration 250 ng/ L. The background-free samples, examined in a total analysis time of 1.5 s/sample, showed good quantitative accuracy and precision, with a relative error (RE) and relative standard deviation (RSD) generally less than 3% and 5%, respectively. The samples in urine and the lipid extract required a longer analysis time (2.5 s/sample) and showed RSD values of around 10% for the samples in urine and 4% for the lipid extract samples and RE values of less than 3% for both sets. The LOD for PRN and CBZ when analyzed without chemical background was 10 and 30 fmol, respectively. The LOD of PRN increased to 400 fmol analyzed in 10% urine, and 200 fmol when analyzed in the brain lipid extract. (J Am Soc Mass Spectrom 2009, 20, 321-325) © 2009 Published by Elsevier Inc. on behalf of American Society for Mass Spectrometry Q uantitative analysis of pharmaceutical compounds in biological fluids is typically carried out using liquid chromatography separation combined with a mass spectrometer fitted with an atmospheric pressure ionization (API) ion source, usually electrospray ionization or atmospheric pressure chemical ionization (LC/ESI-MS or LC/APCI-MS). Such a system can analyze one sample for numerous components in a matter of a few minutes [1]. In most applications, the separation device is directly coupled on-line with the MS. In others, however, extensive prior separation is not necessary, and it can be replaced by a simpler extraction step. In these cases, current highthroughput approaches include direct injection of the sample solution into the MS from a 96-well sample plate for analysis by API [2], or the spotting of solid samples with an organic matrix for analysis by matrix-assisted laser desorption/ionization (MALDI) [3].New options for the ionization of samples at atmospheric pressure have emerged recently. The family of ambient ionization methods for mass spectrometry, which originated with desorption electrospray ionization (DESI) [4] and direct analysis in real time (DART) [5], has rapidly expanded to include a number of new members including MALDESI, LAESI, PADI, ASAP, DBDI, and ELDI [6 -11]. In DESI-MS, samples are analyzed by directing a pneumatically-assisted stream of charged microdroplets at the surface in the ambient...

Desorption electrospray ionization imaging mass spectrometry of lipids in rat spinal cord

“…The home-built DESI ion source is similar to the OmniSpray source from Prosolia Inc. (Indianapolis, IN, USA), configured as described previously [91]. A sprayer-to-surface distance of 2 mm, a sprayer-to-inlet distance of 2.5 mm, an incident angle to the horizontal of 52°and a collection angle of 10°were used.…”

Imaging of human lens lipids by desorption electrospray ionization mass spectrometry

“…DESI-MS was performed on a ThermoFinnigan LTQ mass spectrometer (ThermoScientific, San Jose, CA) coupled to a custom built, 2-D automated DESI source as described elsewhere [27]. The solvent was delivered through a fused silica inner capillary (i.…”

Direct Detection of Pharmaceuticals and Personal Care Products from Aqueous Samples with Thermally-Assisted Desorption Electrospray Ionization Mass Spectrometry

“…The correlation coefficient (R 2 ) resulting from these analyses was 0.9964, and relative standard deviations for all calibration points ranged from 6% to 13%, showing decent precision and linearity for the entire quantitation experiment. Of note, the precision and linearity using Method 2 is comparable to quantitative DESI-MS analyses reported that utilize internal standards and automated positioning systems [40]. The linear dynamic range (LDR) for quantitation of citalopram was approaching three orders of magnitude without utilizing software-controlled automatic gain control (AGC).…”