Identification and Quantification of Transformation Products Formed during the Ozonation of the Non-steroidal Anti-inflammatory Pharmaceuticals Ibuprofen and Diclofenac

Figures & data

Table 1. IBU and detected IBU oxidation products

Product	Structure	Identification method and ionization mode	Fragmentation	Confidence level	References
IBU
OH-IBU		Ion trap MS^2 (+) QqQ (-)	223 -> 205 221 -> 177^a	3	Caviglioli et al. 2002, Chakma and Moholkar 2016, Choina et al. 2013, da Silva 2014, Illés et al. 2013, Li et al. 2014, Sun, Zeng, and Lemley 2013
1-OH-IBU		QqQ, (-)	221 -> 159, 143	1	Caviglioli et al. 2002
2-OH-IBU		QqQ (-)	221 -> 177, 159	1	This study
α-OH-IBU		QqQ (-)	221 -> 175, 133	1	This study
di-OH-IBU		Ion trap (+)	256 (NH4-adduct), 205, 163	3	Chakma and Moholkar 2016, da Silva 2014, Illés et al. 2013, Li et al. 2014, Sun, Zeng, and Lemley 2013
1-OXO-IBU		Ion trap MS^2 (+) QqQ (+)	221 -> 175, 133	1	Caviglioli et al. 2002, Choina et al. 2013
TP192		GC-MS (+) QqQ (-)	263(silylated), 221, 73^b 191 -> 147	1	This study
TP190		GC-MS (+) QqQ (+)	190, 147^b 191 -> 149, 43	1	Caviglioli et al. 2002
TP178		Ion trap (+)	179, 105	3	Caviglioli et al. 2002, Chakma and Moholkar 2016, Choina et al. 2013, Huang et al. 2015, Illés et al. 2013, Li et al. 2014, Sun, Zeng, and Lemley 2013
TP176		Ion trap (+)	194 (NH4-adduct), 151, 173 (NH4-adduct), 119	3	Caviglioli et al. 2002, Choina et al. 2013, Huang et al. 2015, Illés et al. 2013, Li et al. 2014, Sun, Zeng, and Lemley 2013
TP166		Ion trap MS^2 (+)	167 -> 149, 131, 119, 75	3	da Silva 2014
TP134		Ion trap (+)	135, 117, 89	3	Chakma and Moholkar 2016, da Silva 2014, Huang et al. 2015, Illés et al. 2013, Li et al. 2014

a. Product ion scan on the QqQ, b. GC-MS mass spectra.

Table 2. DCF and identified DCF products

Name of product	Sturcture	m/z positive mode	m/z negative mode	Confidence level	References
DCF		[M + H]^+ = 296 m/z = 278, 250, 215	[M-H]^− = 294.0002, C14H11Cl2NO2 (error 2 ppm)^a m/z = 250, 214, 35		This study
5-OH-DCF		[M + H]^+ = 312 m/z = 294, 266, 231	[M-H]^− = 310.0016, C14H10Cl2NO3 (error 7 ppm)^a m/z = 266, 230, 194	1	Monteagudo et al. 2018
4ʹ-OH-DCF		[M + H]^+ = 312 m/z = 294, 266, 231	[M-H]^− = 310.0021, C14H10Cl2NO3 (error 5 ppm)^a m/z = 266, 230, 166	1	Monteagudo et al. 2018
TP312a		[M + H]^+ = 312 m/z = 294, 266, 231, 215, 161		3	Monteagudo et al. 2018, Yu et al. 2013, Hofmann et al. 2007
TP312b		[M + H]^+ = 312 m/z = 294, 266		3	This study
QI-DCF		[M + H]^+ = 310, m/z = 292, 264, 236, 201, 166	307.9904, C14H8Cl2NO3 (error 7 ppm)^a	3	Yu et al. 2013, Zhao et al. 2018, Coelho et al. 2009, Banaschik et al. 2018
TP328a		[M + H]^+ = 328, m/z = 310, 282, 247	325.9995, C14H10Cl2NO4 (error 2 ppm)^a	3	Yu et al. 2013, Coelho et al. 2009
TP326			[M-H]^− = 324 m/z = 280, 244	3	This study
TP282		[M + H]^+ = 282, m/z = 246, 120	279.9927, C13H8Cl2NO2 (error 1 ppm)^a	2b	Monteagudo et al. 2018
TP302			299.9823, C12H8Cl2NO4 (error 3 ppm)^a	3	This study
TP178		[M + H]^+ = 178, m/z = 143		3	Monteagudo et al. 2018, Yu et al. 2013, Coelho et al. 2009, Banaschik et al. 2018, Hartmann et al. 2008
TP328b		[M + H]^+ = 328, m/z = 300		3	This study
TP298			[M-H]^− = 296 m/z = 260, 109	3	This study
TP296		[M + H]^+ = 296, m/z = 278, 250, 215		3	This study
NO2-DCF			[M-H]^− = 339 m/z = 295, 35	1	This study

a. High resolution mass spectrum obtained from the QToF-MS analysis

Figure 1. The ozonation of IBU and the transformation of the main products.

Figure 2. The ozonation of DCF and the transformation of the main products.

Figure 3. Suggested ozonation pathway for IBU.

Figure 4. Suggested ozonation pathway for DCF.

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