Direct quantitation of active ingredients in solid artesunate antimalarials by noncovalent complex forming reactive desorption electrospray ionization mass spectrometry

Abstract

The direct quantitation of active ingredients in solid pharmaceutical tablets by desorption electrospray ionization mass spectrometry (DESI MS) is complicated by the dependence of the DESI signal on variables such as spray angles and distances, morphological sample properties, and the difficulty of properly incorporating an internal standard. Here, a DESI MS method for the direct quantitative screening of widely counterfeited antimalarial tablets containing artesunate is presented. This method is based on reactive DESI, where analyte desorption and ionization occur by the formation of noncovalent complexes between alkylamine molecules in the DESI spray solution and artesunate molecules exposed on the sample surface in the open air. For quantitation purposes, the internal standard d 4 -artesunic acid was synthesized by esterification of d 4 -succinic anhydride and dihydroartemisinin, and homogeneously dispersed on the tablet surface via a controlled deposition procedure. The analyte-to-internal standard signal intensity ratio was observed to be largely independent of all DESI variables, only showing dependence on tablet hardness. Analysis of artesunate tablet standards prepared with known amounts of the active ingredient in the 0.02 to 0.32 mg artesunate mg Ϫ1 tablet range resulted in a calibration curve with good linearity (r ϭ 0.9985). Application of this method to the direct quantitation of genuine artesunate tablets from Vietnam showed a 6% (n ϭ 4) precision and 94% accuracy after the spectral data were corrected for tablet hardness. (J Am Soc Mass Spectrom 2008, 19, 380 -388) © 2008 American Society for Mass Spectrometry T he development of methodologies that allow the quantitative determination of physiologically active an a a aly l l te y y s in i i complex matrices is an ongoing trend in analytical and biological mass spectrometry. In this sense, high-performance liquid chromatography (LC) coupled to mass spectrometry (MS) via electrospray ionization (ESI), or atmospheric pressure chemical ionization (APCI), has become the de facto routine quantitative analytical tool in clinical chemistry, drug discovery, and proteomics [1][2][3]. Although LC-MS is characterized by one of the highest peak capacities of contemporary analytical separation methodologies [4], alternative techniques are constantly being developed to improve sample throughput, eliminate crosscontamination, and increase reproducibility.The emergence of ambient desorption ionization techniques such as desorption electrospray ionization (DESI) [5], direct analysis in real time (DART) [6], and others has enabled the direct sampling of complex solid materials in the open air with minimal or no sample preparation. DESI makes use of a pneumatically assisted electrospray jet, which is directed unto the sample surface to desorb the condensed-phase analyte(s). Following desorption, the analyte-containing charged droplets scattered off the sample surface are sampled by a mass spectrometer. DESI enables the analysis of materials over a large mass range an...

Ambient analysis of saturated hydrocarbons using discharge-induced oxidation in desorption electrospray ionization

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Desorption electrospray ionization mass spectrometry reveals surface-mediated antifungal chemical defense of a tropical seaweed

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Surface analysis of lipids by mass spectrometry: More than just imaging

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