title: Direct analysis in real time--high resolution mass spectrometry as a valuable tool for the pharmaceutical drug development.
abstract: In this study, direct analysis in real time-mass spectrometry (DART-MS) was assessed for the analysis of various pharmaceutical formulations with intention to summarize possible applications for the routine pharmaceutical development. As DART is an ambient ionization technique, it allows direct analysis of pharmaceutical samples in solid or liquid form without complex sample preparation, which is often the most time-consuming part of the analytical method. This makes the technique suitable for many application fields, including pharmaceutical drug development. DART mass spectra of more than twenty selected tablets and other common pharmaceutical formulations, i.e. injection solutions, ointments and suppositories developed in the pharmaceutical industry during several recent years are presented. Moreover, as thin-layer chromatography (TLC) is still very popular for the monitoring of the reactions in the synthetic chemistry, several substances were analyzed directly from the TLC plates to demonstrate the simplicity of the technique. Pure substance solutions were spotted onto a TLC plate and then analyzed with DART without separation. This was the first DART-MS study of pharmaceutical dosage forms using DART-Orbitrap combination. The duration of sample analysis by the DART-MS technique lasted several seconds, allowing enough time to collect sufficient number of data points for compound identification. The experimental setup provided excellent mass accuracy and high resolution of the mass spectra which allowed unambiguous identification of the compounds of interest. Finally, DART mass spectrometry was also used for the monitoring of the selected impurity distribution in the atorvastatin tablets. These measurements demonstrated DART to be robust ionization technique, which provided easy-to-interpret mass spectra for the broad range of compounds. DART has high-throughput potential for various types of pharmaceutical analyses and therefore eliminates the time for sample cleanup and chromatographic separation.
authors.affiliation: Zentiva, k.s. Praha, A Sanofi Company, U Kabelovny 130, 102 37 Praha 10, Czech Republic. Electronic address: jan.srbek@zentiva.cz.
authors.forename: Jan
authors.initials: J
authors.lastname: Srbek
authors.affiliation: Institute of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University in Brno, Zemědělská 1, 613 00 Brno, Czech Republic; CEITEC - Central European Institute of Technology, Mendel University in Brno, Zemědělská 1, 613 00 Brno, Czech Republic.
authors.forename: Bořivoj
authors.initials: B
authors.lastname: Klejdus
authors.affiliation: Zentiva, k.s. Praha, A Sanofi Company, U Kabelovny 130, 102 37 Praha 10, Czech Republic. Electronic address: michal.dousa@seznam.cz.
authors.forename: Michal
authors.initials: M
authors.lastname: Douša
authors.affiliation: Zentiva, k.s. Praha, A Sanofi Company, U Kabelovny 130, 102 37 Praha 10, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Břicháč
authors.affiliation: Zentiva, k.s. Praha, A Sanofi Company, U Kabelovny 130, 102 37 Praha 10, Czech Republic.
authors.forename: Pawel
authors.initials: P
authors.lastname: Stasiak
authors.affiliation: Zentiva, k.s. Praha, A Sanofi Company, U Kabelovny 130, 102 37 Praha 10, Czech Republic.
authors.forename: Josef
authors.initials: J
authors.lastname: Reitmajer
authors.affiliation: Department of Analytical Chemistry, Charles University, Faculty of Pharmacy, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Nováková
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002855:Chromatography, Thin Layer / Q000379:methods; D055808:Drug Discovery; D005079:Excipients / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry*; D013607:Tablets / Q000737:chemistry*
chemical_list: D005079:Excipients; D004364:Pharmaceutical Preparations; D013607:Tablets
keywords: DART mass spectrometry; Impurities; Pharmaceutical formulation