Tracing Origins of Complex Pharmaceutical Preparations Using Surface Desorption Atmospheric Pressure Chemical Ionization Mass Spectrometry

Abstract

A novel strategy to trace the origins of commercial pharmaceutical products has been developed based on the direct chemical profiling of the pharmaceutical products by surface desorption atmospheric pressure chemical ionization mass spectrometry (DAPCI-MS). Besides the unambiguous identification of active drug components, various compounds present in the matrixes are simultaneously detected without sample pretreatment, providing valuable information for drug quality control and origin differentiation. Four sources of commercial amoxicillin products made by different manufacturers have been successfully differentiated. This strategy has been extended to secerning six sources of Liuwei Dihuang Teapills, which are herbal medicine preparations with extremely complex matrixes. The photolysis status of chemical drug products and the inferior natural herd medicine products prepared with different processes (e.g., extra heating) were also screened using the method reported here. The limit of detection achieved in the MS/MS experiments was estimated to be 1 ng/g for amoxicillin inside the capsule product. Our experimental data demonstrate that DAPCI-MS is a useful tool for rapid pharmaceutical analysis, showing promising perspectives for tracking the entire pharmaceutical supply chain to prevent counterfeit intrusions.

Molecular Ionization-Desorption Analysis Source (MIDAS) for Mass Spectrometry: Thin-Layer Chromatography

“…A sheath gas can be used to promote ionization through the introduction of solvents/reagents or, if the gas is heated, through thermal desorption [14,[17][18][19]. Additional DAPCI source descriptions and parameters can be found in a variety of articles [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Examples of applications where DAPCI type sources have been used include hydrocarbons [28], explosives detection [21,29,30], pharmaceuticals [17,24], imaging [31], and natural products [20,23].…”

Analysis of pharmaceutical products and herbal medicines using ambient mass spectrometry

“…Ambient air (without other gas assistance) was generally used as the chemical reagent for DAPCI process, mainly for analysis of small molecular/volatile and semi-volatile compounds. For example, loratidine in Claritin tablet [97], acetaminophen in acetaminophen tablet [97], amoxicillin in amoxicillin capsule [98], aucubin, gallic acid, paeonol, and ursolic acid in Liuwei Dihuang Teapill [98], light-induced degradation products of amoxicillin capsule [98], and monoterpene, sesquiterpenes, and oxy-monoterpene in Fructus schisandrae [99] were all predominately detected by DAPCI-MS via this strategy. Solvents were used widely as chemical reagents to improve the ionization efficiency of analytes in DAPCI process, especially for analysis of large molecular/low volatile compounds.…”

“…For example, CQAs in Erycibe obtusifolia [83], salvianolic acids in Danshen injection [87], and gallic acid and ellagic acid in the extract of Bergenia crassifolia L. leaves [91] were all unambiguously detected by DART-MS. Gallic acid in Liuwei Dihuang Teapill was directly analyzed by DAPCI-MS without sample pretreatment [98].…”

“…The APCI-based ambient ionization techniques such as DART can be utilized to directly analyze some small molecular triterpenoids such as ursolic acid [98]. While for large molecular triterpenoids and saponins such as ginsenosides, they are difficult to be ionized directly by APCI-based ambient ionization methods due to their low volatility and proton affinity.…”

Characterization of a Direct Sample Analysis (DSA) Ambient Ionization Source

“…Other common ambient ionization sources operating on the principles of APCI include desorption atmospheric pressure chemical ionization (DAPCI) [1] and atmospheric solids analysis probe (ASAP) [2]. DAPCI and ASAP sources have been used for a variety of analyses, including explosives [3], food products [4], pharmaceuticals [5,6], and samples of biological origin [7][8][9][10]. These APCI type sources are thought to produce analyte ions primarily through a thermal desorption and proton transfer type mechanism involving the formation of protonated water clusters [11,12], through the well-known APCI ionization cascade [13,14].…”