Detection of Pharmaceuticals by Nitrogen Direct Analysis in Real Time Mass Spectrometry†

doi:10.7503/cjcu20160645

Abstract

Abstract:

Direct analysis in real time-mass spectrometry(DART-MS) was usually employed as a novel method for fast screening of target compounds in complex matrix samples. However, nitrogen direct analysis in real time(N₂-DART) mass spectrometry(MS) analysis of labile compounds usually tends to be challenging because of its low ionization energy and complex background signals. In the current study, N₂-DART ion source coupled with high resolution Orbitrap MS based on a make-up solvent approach, which was designed for analysis of pharmaceuticals sensitively and easily, was reported. The main parameters of ion source, including gas temperature, gas type, scan mode, and solvent effect, were studied. The results confirmed that, compared with conventional He-DART, N₂-DART could generate obviously different ions in positive ion mode. And the sensitivity obtained by N₂-DART was found to be comparable with that obtained by He-DART. Typical mechanisms including the reactions of oxidation and rearrangement in N₂-DART were also discussed in detail. For the purpose of further confirmation, theoretical calculation was employed to verify the feasibility of the rearrangement reaction. The results demonstrated that N₂-DART-MS could provide a rapid and reliable method for the identification of active ingredients in pharmaceuticals, and may be applicable to other mixtures.

Key words: Direct analysis in real time(DART), Orbitrap MS, Active ingredients of pharmaceuticals, Rapid detection

CLC Number:

O654

TrendMD:

SHI Xiaoyu, SU Rui, YANG Hongmei, LIAN Wenhui, WAN Xilin, LIU Shuying. Detection of Pharmaceuticals by Nitrogen Direct Analysis in Real Time Mass Spectrometry^†[J]. Chem. J. Chinese Universities, 2017, 38(3): 362.

Figures/Tables 6

Table 1 Ion information of the 8 selected pharmaceuticals in positive ion mode

Designation	Molecular formula	Molecular mass	Precursor ion	Intensity	Fragment ion	Fragment energy/eV
Chlorpheniramine maleate	C₂₀H₂₃ClN₂O₄	390.1346	275.1303 [M-C₄H₄O₄+H]⁺	2.38×10⁸	230.0727	23
Loratadine	C₂₂H₂₃ClN₂O₂	382.1448	383.1521 [M+H]⁺	2.07×10⁸	337.1109,267.0815	45
Dextromethorphan hydrobromide	C₁₈H₂₅NO·HBr· H₂O	369.1303	272.2005 [M-HBr·H₂O+H]⁺	2.88×10⁸	213.1278,171.0809	40
Terfenadine	C₃₂H₄₁NO₂	471.3137	472.3210 [M+H]⁺	7.00×10⁷	436.3011,454.3087	25
Cimetidine	C₁₀H₁₆N₆S	252.1157	253.1230 [M+H]⁺	4.27×10⁷	159.0703	28
Paeonol	C₉H₁₀O₃	166.0630	167.0703 [M+H]⁺	1.95×10⁷	117.0481	65
Acetaminophen	C₈H₉NO₂	151.0633	152.1406 [M+H]⁺	4.07×10⁷	121.0654,149.0602	55
Butyl flufenamate	C₁₈H₁₈F₃NO₂	337.1290	338.1362 [M+H]⁺	2.64×10⁸	135.1173	18

Fig.1 N2-DART orbitrap mass spectra of 8 pharmaceuticals in positive ion mode (A) Chlorpheniramine maleate; (B) loratadine; (C) dextromethorphan hydrobromide; (D) terfenadine; (E) cimetidine; (F) paeonol; (G) acetaminophen; (H) butyl flufenamate.

Fig.2 Mass spectra of loratadine obtained using helium(A), argon(B) and nitrogen(C) as DART carrier gas

Fig.3 Influence of three solvents with different concentrations on signal intensities obtained for cimetidine in positive ion mode Data points are mean values of three determinations.

Fig.4 Probable fragmentation mechanism in N2-DART MS (A) Oxygen addition products of cimetidine; (B) oxygen addition product of paeonol; (C) rearrangement reactions of paeonol; (D) rearrangement reaction of chlorpheniramine maleate; (E) dehydration reaction of terfenadine.

Fig.5 Potential energy diagrams for the fragmentation and rearrangement reaction of paeonol

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