Assessment of paper tip angular position, carryover, matrix effects and dried blood spot storage effect on paper spray mass spectrometry

Abstract

Paper Spray (PS) ionization has been demonstrated extensively for rapid quantitation of pharmaceuticals in dried matrix spots. In this study, experimental and validation parameters of paper spray mass spectrometry were explored. Firstly, the effect on analyte signal response by angular positioning of the paper/spray tip to the mass spectrometer (MS) inlet was studied and found that, the analyte signal response depends on the flow rate of the paper substrate, when the spray tip is positioned in angle to the MS inlet. Secondly, the extent of carryover on the PS system due to the reuse of the paper substrate metal clip holder was evaluated and found to be compound dependent and could be minimal for some compounds even when the metal clip holder is reused. Thirdly, the blood matrix effects in different paper substrates on analyte signal was evaluated and found that, in the absence/presence of a matrix, the absolute signal response/suppression of the analytes varied significantly among the papers. Moreover, the precision value of standard line slopes constructed in six different lots of rat blood was 2.2%, less than the cut-off value of <3–4%, indicating matrix effects in PS-MS could be effectively controlled by the use of a stable isotope labelled internal standard. Finally, a storage effect study on analyte elution from dried blood spots (DBS) showed that DBS storage could impact both analyte extraction and detection sensitivity; hence, pre-moistening of the dried spots with spray solvent prior to MS analysis could minimize this effect on analyte signal response.