sitagliptin and photo-transformation products in
TRANSCRIPT
D:\ENELTON\...\SGT_09H_HPLC_PHOTO7 09/26/19 14:39:37
SGT_09H_HPLC_PHOTO7 #957 RT: 2.28 AV: 1 SB: 6 1.77-2.18 , 2.38-2.75 NL: 1.46E6F: FTMS + p ESI d Full ms2 [email protected] [50.0000-260.0000]
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174.0527
234.0741
SGT_09H_HPLC_PHOTO7_20191114 11/14/19 17:32:41
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406.1306
C 16 H17 O2 N5 F 5
8.5 RDBE2.2725 ppm
235.0807
C 13 H11 O N F 2
8.0 RDBE1.4294 ppm
172.0571
C 8 H8 O N F 2
4.5 RDBE1.7281 ppm
120.0810
C 8 H10 N
4.5 RDBE1.6228 ppm
318.1816
406.1306
346.1095
389.1033269.1107 329.0826
NL: 6.13E5
SGT_09H_HPLC_PHOTO7_20191114#1104 RT: 2.40 AV: 1 F: FTMS + p ESI d Full ms2 [email protected] [50.0000-435.0000]
NL: 1.47E6
SGT_09H_HPLC_PHOTO7_20191114#1306 RT: 2.85 AV: 1 F: FTMS + p ESI d Full ms2 [email protected] [50.0000-435.0000]
Sitagliptin and photo-transformation products in freshwater by LC-HRMS (Orbitrap)
Enelton Fagnani(1,2), Olga Gómez Navarro (2)*, Nicola Montemurro(2), Sandra Pérez(2)
(1) School of Technology, University of Campinas (UNICAMP), Paschoal Marmo 1888, 13484-332 Limeira-SP, Brazil(2) Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research from the Spanish Council for Scientific Research
(IDAEA-CSIC), Jordi Girona 18-26, 08034 Barcelona, Spain* [email protected] Tel.: +34-934-006-100, Fax: +34-932-045-904
Grant #2018/09875-3
Acknowledgements
The identified photo-TPs of SGT in lab experiments were not found in these first Llobregat river samples. SGTs photo-TPs will be searched in samples from future sampling campaigns.
ReferencesMatuszewski et al. Anal. Cheml. 75 (2003) 3019-3030, doi: 10.1021/ac020361s
Meckelke et al. Anal. Bioanal. Chem. 411 (2019) 2555-2567, doi: 10.1007/s00216-019-01696-3
Hermes et al. Environ. Sci. Technol. 54 (2020) 10588-10598, doi: 10.1021/acs.est.0c01454
Conclusion
Sitagliptin (SGT, logP: 1.26) is an organofluorinated pharmaceutical used to treat Type 2 Diabetes. In the past years, its consumption has increased andbiological recalcitrance has been recognized. SGT has very low human metabolic rate, entering the wastewater treatment plants (WWTPs) unchanged.In addition, conventional treatments barely degrade SGT which can therefore be found in the aquatic system at concentrations of ng L-1 or higher.Natural solar photolysis assumes importance as a possible degradation process for many pharmaceutical products, including SGT. Exposure to sunlightactivates degradation processes with the consequent production of photo-transformation products (photo-TP) that can accumulate in freshwater.Since photo-TPs may have greater ecotoxicity than their precursors, their study and identification is essential to assess the health of a watercourse.In this work, the fate of SGT and its photo-TPs both in lab-scale photolysis simulation and in freshwater samples will be studied.
Introduction
Methodology
Solar sunlightsimulator
Irradiation time: 3 and 9 h
Suntest CSP Haereus
(600W/m2)
Quartzcubette
Al foil
Multi-layer SPE cartridge
LC-MS/MS Q-Exactive Orbitrap
Photolysis of SGT
41020´58.5”N 2002´46.7”E
SGT UV spectrumSampling campaign(Llobregat river)
ExtractionFor a wide range of log Kow
No pH adjustments are needed
SGT photo-TPs production1 ppm or 10 ppm
Results and Discussion
Lab photolysis simulation
Kinetic degradation for SGT and photo-TPs
In lab simulation, SGT was identified even after 9h ofphotolysis, proving its high recalcitrance. However, 10photo-TPs were also identified.
Llobregat river samples
SGT was identified and quantified at a concentration of 398 ng L-1.
MS/MS spectrum SGT 233 (amide hydrolysis)
MS/MS spectrum SGT
MS/MS spectrum SGT 405 (-F+OH)
Loss of NH3
Triazole-piperazinemoiety
Benzyl site withprimary amine
TP 405
Benzyl site withprimary amine
TP 233
Triazole-piperazinemoiety
Photo-TP identified in lab simulation were not found in Llobregat river samples.
SGT_09H_HPLC_PHOTO7_20191114 11/14/19 17:32:41
50 100 150 200 250 300 350 400
m/z
0
10
20
30
40
50
60
70
80
90
100
0
10
20
30
40
50
60
70
80
90
100
Re
lative
Ab
un
da
nce
406.1306
C 16 H17 O2 N5 F 5
8.5 RDBE2.2725 ppm
235.0807
C 13 H11 O N F 2
8.0 RDBE1.4294 ppm
172.0571
C 8 H8 O N F 2
4.5 RDBE1.7281 ppm
120.0810
C 8 H10 N
4.5 RDBE1.6228 ppm
318.1816
406.1306
346.1095
389.1033269.1107 329.0826
NL: 6.13E5
SGT_09H_HPLC_PHOTO7_20191114#1104 RT: 2.40 AV: 1 F: FTMS + p ESI d Full ms2 [email protected] [50.0000-435.0000]
NL: 1.47E6
SGT_09H_HPLC_PHOTO7_20191114#1306 RT: 2.85 AV: 1 F: FTMS + p ESI d Full ms2 [email protected] [50.0000-435.0000]