Rapid simultaneous quantitative determination of different small pharmaceutical drugs using a conventional matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry system

The present study establishes a simple, rapid and sensitive method for the simultaneous quantification of different small pharmaceutical drugs using a matrix-assisted laser desorption/ionization source (MALDI) coupled with a time-of-flight (TOF) mass analyzer. Neither time-consuming sample preparation, nor special target plates, isotopically labelled internal standards or other extra equipment are necessary. A simple standard dried-droplet preparation with the common matrix alpha-cyano-4-hydroxycinnamic acid (CHCA) was used. The background signals of CHCA in the low-mass region did not pose the presumed problem, because the sensitivity, resolution and mass accuracy of a modern MALDI-TOF MS system is sufficient to overcome this difficulty. Four experiments were performed in order to verify the quantification method. First, ten different phenothiazines were quantified in the range of 5-2000 nM (1-880 ng/mL). A good precision (relative standard deviation (RSD) 4.4-9.3%), linearity (R2 >0.99) and accuracy (error 4.7-11%) was obtained in all cases. Additionally, simultaneous quantification of these ten phenothiazines was carried out in human plasma without prior chromatographic separation in the range of 2-1750 ng/mL yielding good linearity, precision and accuracy (mean RSD 7.6%; R2 >0.99, mean error 8.0%). Accordingly, a quantitative analysis of ten chemically and pharmaceutically unrelated drugs was performed in the same way. A comparable linearity (R2 >0.99), precision (mean RSD 7.6%) and accuracy (mean error 8.3%) was obtained in the range of 5-2000 nM. Finally, the prazosin content of a commercial tablet was directly determined without further purification steps.