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Analytical strategy to investigate 3,4-methylenedioxypyrovalerone (MDPV) metabolites in consumers’ urine by high-resolution mass spectrometry

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S-1

ELECTRONIC SUPPLEMENTARY MATERIAL

ANALYTICAL STRATEGY TO INVESTIGATE 3,4-

METHYLENEDIOXYPYROVALERONE (MDPV) METABOLITES IN CONSUMERS’ URINE BY HIGH RESOLUTION MASS

SPECTROMETRY

María Ibáñez1*, Óscar J. Pozo2, Juan V Sancho1, Teresa Orengo3, Gonzalo Haro4,5,Félix Hernández1

1Research Institute for Pesticides and Water, University Jaume I, Avda. SosBaynat, E- 12071 Castellón, Spain.

2Bioanalysis Research Group, IMIM, Hospital del Mar Medical Research Institute, Doctor Aiguader 88, 08003 Barcelona, Spain

3Addictions Treatment Unit Grao-Clínico, Valencia, Spain

4School of Medicine, University CEU-Cardenal Herrera, Castellón

5Psychiatry Department, Consorcio Hospitalario Provincial de Castellón

* Corresponding author [email protected], Tel +34 964 387339, Fax +34 964 387368

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S-2 Fig S.1. Extracted Ion Chromatograms (XICs) for all detected metabolites.

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S-3 Metabolite M1

Figure S.2. Product ion spectrum of M1 (20 eV) and proposed fragmentation pathway.

m/z 193 m/z 264

m/z 175 M1

- H2O - - CH3CH2CH2

N H

O

O

m/z 137 m/z 221

N m/z 264

m/z 126

N H

m/z 126

H N H

m/z 84 m/z 193

m/z 123

O

HO N HO

O

HO N HO

H O

HO N HO

H

O

O HO H

O

HO HO

O

HO N HO

H

N H H

m/z 72

HO HO

O H

HO

HO m/z 165

- CO

HO HO

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S-4 Figure S.3. Product ion spectrum of M2 (20 eV) and proposed fragmentation pathway.

m/z 207 m/z 278

m/z 175 M2

- H2CO - - CH3CH2CH2

N H

O

O

m/z 151 m/z 235

N m/z 278

m/z 126

N H

m/z 126

H N H

m/z 84

m/z 207

m/z 137

O

HO N CH3O

O

HO N CH3O

H

O

HO N CH3O

H

O

O CH3O H

O

HO CH3O

O

HO N CH3O

H

HO CH3O

O H

HO CH3O

(5)

S-5 Metabolite M3

Figure S.4. Product ion spectrum of M3 (20 eV) and proposed fragmentation pathway.

O

HO N HO

m/z 193 m/z 278

m/z 175 M3

- H2O - - H2O

O

O

m/z 137

m/z 278

m/z 140 m/z 140

m/z 98

m/z 193

m/z 123

O

O HO H

O

HO HO

m/z 86

HO HO

O H

HO HO m/z 278

O

HO N HO

OH

H H

m/z 260

O

HO N HO

O

N H

O

O

HO N HO

H

O

N O O N H

H N H

O O

HO N HO

H O

N H

H O

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S-6

O

HO NH CH3O

H

O HO O

HO NH CH3O

O HO

m/z 292 M5

m/z 140 m/z 140

m/z 98

N O O N H

H N H

O - N

H O m/z 310

O HO m/z 87

- H2O

m/z 310

NH

O HO m/z 158 O

NH2 HO

CH3O

O HO

O

HO N CH3O

H O

m/z 207

m/z 175 - H2CO

O

O

m/z 151 m/z 207

m/z 137

O

O CH3O

H

O

HO CH3O HO

CH3O

O H

HO CH3O

O HO m/z 87

- NH3 m/z 104

O HO

NH3

O

HO NH CH3O

O HO

NH2 O

NH O

NH

O OH O

N O

O HO

CH3O

N O

H

HO CH3O

NH

O OH

HO CH3O

NH OH

O OH HO

CH3O

NH OH

O OH O

HO NH CH3O

H

O HO M5

- H2O

m/z 310 m/z 310 m/z 310

- H2O

m/z 292

O O

-

- H2CO

O O

- - H2CO

- H2O

m/z 206 m/z 260

- H2CO m/z 242

m/z 274

m/z 174 - HCOOH

m/z 214 m/z 232

-

HO CH3O

NH2 HO

CH3O

N O

HO CH3O

NH m/z 205

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S-7 Figure S.5. Product ion spectrum of M5 (20 eV) and proposed fragmentation pathway.

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S-8 Figure S.6. Product ion spectrum of M6 (20 eV) and proposed fragmentation pathway.

m/z 207 m/z 292

m/z 175 M6

- CH3OH -

- H2O

O

O

m/z 292

m/z 140 m/z 140

m/z 98

m/z 207

m/z 86 m/z 292

m/z 274

N H

O

N O O N H

H N H

O N

H H O

m/z 137

O

CH3O N HO

O

O

CH3O N HO

H

O

O

CH3O N HO

H O

O

CH3O O H O

CH3O N HO

OH

H H

O

CH3O N HO

CH3O HO

O H

CH3O HO

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S-9 Metabolite M7

Figure S.7. Product ion spectrum of M7 (20 eV) and proposed fragmentation pathway.

m/z 207 m/z 292

m/z 175 M7

- CH3OH -

- H2O

O

O

m/z 292

m/z 140 m/z 140

m/z 98

m/z 207

m/z 86 m/z 292

m/z 274

N H

O

N O O N H

H N H

O N

H H O

m/z 137 HO CH3O

O

HO N CH3O

O

O

HO N CH3O

H

O

O

HO N CH3O

H O

O

O CH3O H HO

CH3O

O H O

HO N CH3O

OH

H H

O

HO N CH3O

(10)

S-10 Figure S.8. Product ion spectrum of M8 (20 eV) and proposed fragmentation pathway.

m/z 189 m/z 217

m/z 175

M8

- H2O -

- CH3CH2CH2 N

H

m/z 159 m/z 278

m/z 260

m/z 207

N H H

m/z 72

OH

O N O

OH2

O N O

m/z 278

O N O

- H2O OH

O N O

H

OH

O

O H

- CH3OH

- H2CO

O N O

O O

O O

O

N

m/z 126

N H

m/z 126

H N H

m/z 84

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S-11 Metabolite M9

HO CH3O

O H

O

HO N CH3O

H

m/z 205

m/z 173

M9

- H2CO

- N

H

m/z 294

m/z 142

m/z 205

m/z 137 HO CH3O

O

HO N CH3O

OH O

HO N CH3O

H OH

N OH m/z 294

- H2O O

HO N CH3O

H OH

- CH3CH=CH2

O

O CH3O

H

m/z 151 O

HO CH3O m/z 276

- N

H

O

HO N CH3O

m/z 234

O

O CH3O

H

m/z 205

O CH3O H

O

m/z 205

- CH2=CH2 O CH3O H

O

m/z 177 - H2O

O

HO CH3O

OH

m/z 223

- H2O

m/z 216 O

N O

O

O

M9

O

HO N CH3O

OH

m/z 294 O

HO N CH3O

H OH

- H2O

m/z 276 - CO

N H

m/z 98 m/z 248

- CH4

H N

HO CH3O

m/z 232 - CH3OH

O

H N

m/z 200 - CHCH

N H H

m/z 72

O

CH3O N

H

H

H O

HO N CH3O

H

(12)

S-12 Only fragmentation corresponding to one of the two possible candidates (concretely, 1- (4-hydroxy-3-methoxyphenyl)-3-hydroxy-2-(1-pyrrolidinyl)pentan-1-one) is shown, but the implied pathways for both candidates will be “identical”.

(13)

S-13 Metabolite M10

Figure S.10. Product ion spectrum of M10 (20 eV) and proposed fragmentation pathway. Only fragmentation corresponding to the most feasible candidate (concretely 1-(4-hydroxy-3-methoxyphenyl)-2-(2-hydroxypyrrolidinyl)pentan-1-one is shown, but the implied pathways for both candidates will be “identical”.

m/z 207 m/z 294

m/z 175 M10

- H2CO

- - CH3CH2CH2

O

O

m/z 151 m/z 276

m/z 294

m/z 142 m/z 142

m/z 100

m/z 207

m/z 137

O

O CH3O

H

O

HO CH3O HO

CH3O

O H

HO CH3O

O

HO N CH3O

H

OH

N OH HO N H

H N H

OH N

H

OH O

HO N CH3O

H OH

N H H

OH

m/z 88 - H2O

m/z 70 N H

H O

HO N CH3O

OH

- H2O O

HO N CH3O

H m/z 251

O

HO N CH3O

H OH

m/z 248 CH3O N H

HO

Referencias

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