Supplementary Data
Collision-Induced Dissociation Pathways of H1-Antihistamines by Electrospray Ionization Quadrupole Time-of-Flight Mass Spectrometry
Jung-Ah Do1, Eunyoung Noh1, Soon-Byung Yoon1, Ji Hyun Lee1, Sung-Kwan Park1, Suresh Mandava2, Sun Young Baek1,*, Jongkook Lee2,*
1Advanced Analysis Team, Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju-si 28159, Republic of Korea
2College of Pharmacy, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon, Gangwon-do 24341, Republic of Korea
Contents
1. Supplementary Table S1–S3
2. Supplementary Fig. S1–S7
3. MS2 spectra of H1-antihistamines
1. Supplementary Tables
Table S1 Structural classification of H1-antihistamines
Classification / H1-AntihistaminesGroup 1
Alkylamines / Chloropheniramine
Bromopheniramine
Allylamines / Acrivastine
Triprolidine
Piperazines / Cetrizine (levocetrizine)
Hydroxyzine
Aminoethers / Diphenhydramine
Ebastine
Clemastine
Piperidines / Fexofenadine
Terfenadine
Group 2
Tricyclic compounds / Loratadine
Desloratadine
Cyproheptadine
Ketotifen
Olopatadine
Promethazine
Group 3
Others / Azelastine
Astemizole
Epinastine
Table S2 Molecular weights (MW) and calculated mass values (m/z) for protonated molecules [M+H]+ and the distinguishable fragment ions
H1-antihistamines / MW / [M+H]+ / Frag. 1 / Frag. 2 / Frag. 3 / Frag. 4 / Frag. 5Acrivastine / 348.438 / 349.192 / 278.118 / 260.108 / 232.113
Astemizole / 458.570 / 459.256 / 308.156 / 242.109 / 218.154 / 135.081
Azelastine / 381.898 / 382.169 / 271.064 / 112.113
Bromopheniramine / 319.239 / 319.081 / 274.023 / 167.073
Cetirizine / 388.889 / 389.163 / 201.047 / 166.078
Chloropheniramine / 274.788 / 275.132 / 230.074 / 167.063
Clemastine / 343.890 / 344.178 / 215.063 / 180.094 / 137.016 / 130.123
Cyproheptadine / 287.398 / 288.175 / 215.086 / 191.086
Desloratadine / 310.821 / 311.132 / 294.105 / 282.105 / 259.136
Diphenhydramine / 255.356 / 256.170 / 167.086
Ebastine / 469.658 / 470.306 / 203.144 / 167.086
Epinastine / 249.310 / 250.134 / 231.092 / 193.089 / 178.078 / 165.070
Fexofenadine / 501.656 / 502.296 / 484.285 / 466.275 / 171.117 / 131.086
Hydroxyzine / 374.904 / 375.184 / 201.047 / 166.078
Loratadine / 382.883 / 383.153 / 337.111 / 294.105 / 280.089 / 267.081 / 259.136
Ketotifen / 309.425 / 310.127 / 221.042 / 213.037 / 197.042
Olopatadine / 337.412 / 338.176 / 293.118 / 247.112 / 165.055
Promethazine / 284.419 / 285.143 / 240.085 / 198.038
Terfenadine / 471.673 / 472.322 / 454.311 / 436.300 / 262.160
Triprolidine / 278.391 / 279.186 / 208.113 / 193.089
Table S3 Mass error in ppm for protonated molecules [M+H]+ and the distinguishable fragment ions
H1-antihistamines / [M+H]+ / Frag. 1 / Frag. 2 / Frag. 3 / Frag. 4 / Frag. 5Acrivastine / 26 / 4 / 0 / 17
Astemizole / 2 / 3 / 8 / 0 / 0
Azelastine / 5 / 0 / 0
Bromopheniramine / 6 / 0 / 6
Cetirizine / 2 / 5 / 0
Chloropheniramine / 22 / 9 / 42
Clemastine / 29 / 5 / 6 / 7 / 0
Cyproheptadine / 14 / 5 / 5
Desloratadine / 0 / 10 / 4 / 0
Diphenhydramine / 12 / 6
Ebastine / 0 / 0 / 0
Epinastine / 0 / 4 / 0 / 0 / 0
Fexofenadine / 10 / 10 / 11 / 29 / 46
Hydroxyzine / 3 / 5 / 0
Loratadine / 3 / 0 / 3 / 0 / 0 / 0
Ketotifen / 0 / 5 / 5 / 5
Olopatadine / 6 / 24 / 0 / 12
Promethazine / 4 / 4 / 5
Terfenadine / 17 / 11 / 16 / 8
Triprolidine / 7 / 5 / 5
2. Supplementary Figures
Fig. S1 Structures of 21 H1-antihistamines
Fig. S2 Proposed fragmentation pathway for triprolidine
Fig. S3 Proposed fragmentation pathway for clemastine
Fig. S4 Proposed fragmentation pathway for terfenadine
Fig. S5 Proposed fragmentation pathways for cyproheptadine and ketotifen
Fig. S6 Proposed fragmentation pathways for olopatadine and promethazine
Fig. S7 Proposed fragmentation pathway for epinastine
3. MS2 spectra of H1-antihistamines
Acrivastine
Astemizole
Azelastine
Brompheniramine
Cetirizine
Chlorpheniramine
Clemastine
Cyproheptadine
Desloratadine
Diphenhydramine
Ebastine
Epinastine
Fexofenadine
Hydroxyzine
Ketotifen
Loratadine
Olopatadine
Promethazine
Terfenadine
Triprolidine
6