Is it a fentanyl?

Arun Moorthy -- asm3@nist.gov

Mass Spectrometry Data Center -- chemdata.nist.gov

Collaborators: WE Wallace, WG Mallard, SE Stein –Mass Spec Data Center, BMD, MML

AJ Kearsley – Applied and Computational Math Division, ITL
(History) Phenyl fentanyl

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

42 51 65

77

91

105

118 130 146

158 180 197

250

267 279

293

327 341

fragment-ion m/z

abundance

A mass spectrum is a histogram detailing the distribution of fragment ions

organized by mass-to-charge ratio for a given compound.
(History) Phenyl fentanyl

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

42 51 65

77

91

105

118 130 146 158 180 197

250

267 279

293

327 341

Mass Spectral Library Searching

Principle: Given a set (library) of mass spectra for known chemical compounds, the identity of an 

unknown chemical compound can be proposed by comparing the similarity of the spectrum of 

the unknown with the spectra contained in the library.

(replib) Fentanyl

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

42

51

57

70

77

91

105

118

132

146

158

189

202

223

245

253 266 282 310 334

(swgdrug 3.3) Benztropine

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

42

55

67 77

83

96

110

124

140

152

165 201

216 244 307

(swgdrug 3.3) 1-Benzylpiperazine-d7

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

42

56

66

70

85

98

109 127

141

152 164

183

(mainlib) Cyclopentanone, 3-methyl-2-pentyl0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

41 55

69

83

98

110

123 137

153

168

(mainlib) Cyclohexanamine, 5-methyl-2-(1-methylethyl)-, (1α,2α,5β)-

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

41 56

70

81 98

112

140

155

(mainlib) Azacyclohex-3-en-5-one, 1-tert-butyl-3-methyl0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

41 57

70

82

86

95

110

124

152

167

(mainlib) Cyclohexane, 1,3,5-trimethyl0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

14

27

41

55

69

83 95

111

126

(mainlib) 3-Hexene, 3-methyl-, (E)-

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

15

27

41

55

69

83

91

98

(mainlib) 2-Propen-1-one, 1-cyclopropyl0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

27

41

55

69

81

96

(mainlib) Cyclobut-1-enylmethanol

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

27 39

55

65

83

(mainlib) 3-Oxatricyclo[4.1.1.0(2,4)]octane, 2,7,7-trimethyl0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

27

41

55

67

83

95

109

119

137

152

(mainlib) 1H-Benzocycloheptene, 2,4a,5,6,7,8,9,9a-octahydro-3,5,5-trimethyl-9-methylene0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

27

41

55

69 79

93

105

119

134

147

161

175

189 204

(mainlib) Phenanthrene, 7-ethenyl-1,2,3,4,4a,4b,5,6,7,8,10,10a-dodecahydro-4a,7-dimethyl-1-methylene-, [4aS-(4aα,4aβ,7β,10aβ)]-

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

15

29

41

55

67

79

91

105

119 131

145

157 171 186

199

213

227

241

256

(mainlib) Dibenzo[a,h]cyclotetradecene, 2,3,11,12-tetraethenyl-1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18-octadecahydro-, (2R*,3S*,4Z,9Z,11R*,1

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

29

41

55

67

79 91

105

117 131 145

159

171 185

199

213 225 239 253 267 279 293 309 321 333

350

(mainlib) 1,5-Cycloundecadiene, 8,8-dimethyl-9-methylene0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

27

41

55

67

79

93

107

121

134

147

161

175

190

Library Search 

Algorithm

Hitlist
(History) Phenyl fentanyl

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

42 51 65

77

91

105

118 130 146 158 180 197

250

267 279

293

327 341

(mainlib) 1-Benzoyl-3-benzyl-2-t-butyl-5-methyl-imidazolidin-4-one

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

29 41 51 65

77

91

97

105

117 130 142 159 174 189 203 264

293

307 335

O

N

N

O

(mainlib) 4-Imidazolidinone, 1-benzoyl-2-(1,1-dimethylethyl)-3-methyl-5-(phenylmethyl)-, (2R-cis)-

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

29 42 51 65

77

82 91

105

120 149

293

335

N N

O

O

(mainlib) 2-Phenyl-4-piperonylidene-2-oxazolin-5-one

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

51

62

77

88

105

114 130 145 160 177 190 206 248

293

N

O O O

O

(mainlib) N-(3-Methyl-2-oxo-5-phenyl-2,3-dihydrofuran-3-yl)benzamide

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

18 28 42

51

63

77

91

105

115 131 144

160

173 188 209 221 234

249

264 278 293

O O

NH

O

1. (795)

2. (726)

3. (685)

4. (625)

Simple Similarity Search of 

query against NIST17 
(mainlib) 1-Benzoyl-3-benzyl-2-t-butyl-5-methyl-imidazolidin-4-one

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

29 41 51 65

77

91

97

105

117 130 142 159 174 189 203 264

293

307 335

O

N

N

O

(mainlib) 4-Imidazolidinone, 1-benzoyl-2-(1,1-dimethylethyl)-3-methyl-5-(phenylmethyl)-, (2R-cis)-

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

29 42 51 65

77

82 91

105

120 149

293

335

N N

O

O

(mainlib) 2-Phenyl-4-piperonylidene-2-oxazolin-5-one

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

51

62

77

88

105

114 130 145 160 177 190 206 248

293

N

O O O

O

(mainlib) N-(3-Methyl-2-oxo-5-phenyl-2,3-dihydrofuran-3-yl)benzamide

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

18 28 42

51

63

77

91

105

115 131 144

160

173 188 209 221 234

249

264 278 293

O O

NH

O

1. (795)

2. (726)

3. (685)

4. (625)

(History) Phenyl fentanyl

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

42 51 65

77

91

105

118 130 146 158 180 197

250

267 279

293

327 341

Simple Similarity Search of 

query against NIST17 

Match Factor
(History) Phenyl fentanyl

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

42 51 65

77

91

105

118 130 146 158 180 197

250

267 279

293

327 341

Simple Similarity Search of 

query against NIST17 (mainlib) 1-Benzoyl-3-benzyl-2-t-butyl-5-methyl-imidazolidin-4-one

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

29 41 51 65

77

91

97

105

117 130 142 159 174 189 203 264

293

307 335

O

N

N

O

(mainlib) 4-Imidazolidinone, 1-benzoyl-2-(1,1-dimethylethyl)-3-methyl-5-(phenylmethyl)-, (2R-cis)-

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

29 42 51 65

77

82 91

105

120 149

293

335

N N

O

O

(mainlib) 2-Phenyl-4-piperonylidene-2-oxazolin-5-one

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

51

62

77

88

105

114 130 145 160 177 190 206 248

293

N

O O O

O

(mainlib) N-(3-Methyl-2-oxo-5-phenyl-2,3-dihydrofuran-3-yl)benzamide

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

18 28 42

51

63

77

91

105

115 131 144

160

173 188 209 221 234

249

264 278 293

O O

NH

O

1. (795)

2. (726)

3. (685)

4. (625)
What if a spectrum of the unknown was not contained in the library?
Hybrid Similarity What if a spectrum of the unknown is not contained in your library?
• Combines fragment ion AND neutral loss matching when computing 

spectral similarity 

– DeltaMass = Δmm= MW(Query Compound) – MW(Library Compound)

– Compare each query peak to two peaks in the library spectrum at 

corresponding:

• (1) m/z [match suggests compounds form same fragment ion]

• (2) m/z + DeltaMass [match suggests compounds form same neutral loss]

• Generates high spectral similarity scores between compounds that differ 

by the insertion/deletion or replacement of a single chemical moiety that 

does not greatly affect fragmentation mechanism (cognates)

Hybrid Similarity
Fentanyl Head to Tail MF=346 RMF=445 para-Methylfentanyl

0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 270 280 290 300 310 320 330 340 350 360 370 380

0

50

100

50

100

15

29 42

42

57

57

70

70

77

77

82

91

91

105

105

118

118

132

132

146

146

158

160

172

172 186

189

202

203

216

216

230 241

245

259

279

281 293 348

N

O N

N

O N

MF = 346
Fentanyl Head to Tail MF=963 RMF=963 para-Methylfentanyl

0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 270 280 290 300 310 320 330 340 350 360 370 380

0

50

100

50

100

15

29 42

42

57

57

70

70

77

77

82

91

91

105

105

118

118

132

132

146

146

158

160

172

172

189

189

202

203

216

216

230

245

245 259

279

279 293 348

N

O N

Mass shift = -14

Neutral loss 

matching peak Shifted peak

Fragment Ion 

matching peak

N

O N

hMF = 963
• Combines fragment ion AND neutral loss matching when computing 

spectral similarity 

– DeltaMass = Δmm= MW(Query Compound) – MW(Library Compound)

– Compare each query peak to two peaks in the library spectrum at 

corresponding:

• (1) m/z [match suggests compounds form same fragment ion]

• (2) m/z + DeltaMass [match suggests compounds form same neutral loss]

• Generates high spectral similarity scores between compounds that differ 

by the insertion/deletion or replacement of a single chemical moiety that 

does not greatly affect fragmentation mechanism (cognates)

Hybrid Similarity
(History) Phenyl fentanyl

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

42 51 65

77

91

105

118 130 146 158 180 197

250

267 279

293

327 341

(mainlib) 1-Benzoyl-3-benzyl-2-t-butyl-5-methyl-imidazolidin-4-one

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

29 41 51 65

77

91

97

105

117 130 142 159 174 189 203 264

293

307 335

O

N

N

O

1. (934)

Δmm = 10

2. (822)

Δmm = 32

3. (820)

Δmm = 34

6. (787)

Δmm = 50

Hybrid Similarity Search of 

query against NIST17 (mainlib) Furanylfentanyl

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

42

51 65

77

95

105

118 130

144

158

170

187

212

240

253 265

283

315 327 341

N

O

O

N

(mainlib) N-Phenyl-1-(2-phenylethyl)-4-piperidinamine, N-trimethylsilyl0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

15 28

44

59

73

77

84

91

96

105

116

132

146 160

187 204

218

231 245

261

309 337

N

Si

N

(mainlib) Acrylfentanyl

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

15 27

42

55

70

77 96

105

118

132

146

158

172

189

200

214

243

279 333

N

O

N
(History) Phenyl fentanyl

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

42 51 65

77

91

105

118 130 146 158 180 197

250

267 279

293

327 341

(mainlib) 1-Benzoyl-3-benzyl-2-t-butyl-5-methyl-imidazolidin-4-one

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

29 41 51 65

77

91

97

105

117 130 142 159 174 189 203 264

293

307 335

O

N

N

O

1. (962)

Δmm = −6

2. (938)

Δmm = 10

3. (937)

Δmm = 10

4. (936)

Δmm = 10

Hybrid Similarity Search of 

query against SWGDRUG 3.3 (mainlib) Furanylfentanyl

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

42

51 65

77

95

105

118 130

144

158

170

187

212

240

253 265

283

315 327 341

N

O

O

N

(mainlib) N-Phenyl-1-(2-phenylethyl)-4-piperidinamine, N-trimethylsilyl0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

15 28

44

59

73

77

84

91

96

105

116

132

146 160

187 204

218

231 245

261

309 337

N

Si

N

(mainlib) Acrylfentanyl

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

15 27

42

55

70

77 96

105

118

132

146

158

172

189

200

214

243

279 333

N

O

N

(swgdrug 3.3) Thiofuranyl fentanyl

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

42

51 65

77

91 105

111

130 146

158

172 186 207

256

279

299

341

N

S

N

O

(swgdrug 3.3) Cyclopentenyl fentanyl

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

42

51

67

77

95

105

118 130

146

158 170

189

207 240

253 265

283

327 343

N

N

O

(swgdrug 3.3) 3-Furanyl fentanyl

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

30

42

55 67

77 91

95

105

118 130 146

158

170 186 212

240

254

283 N

O N

O

(swgdrug 3.3) 2-Furanyl fentanyl

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

42

51 65

77

95

105

118 130

144

158

170

187

212

240

253 265

283

313 325 341

O N

O N

Libraries 

matter!
Can we do more?
Fentanyl What if a spectrum of the unknown is not contained in your lib ClassifieR
Fentanyl What if a spectrum of the unknown is not contained in your lib ClassifieR (prototype)
Fentanyl ClassifieR (prototype)

Objective: Make mass spectral library searching “easier” by re-casting our search question.

Trivial example: 

Here is an exotic fruit, what is it? 

Hard question – requires knowledge of all fruit

Here is an exotic fruit, is it an apple?

Easier question – requires knowledge of all apples
Objective: Make mass spectral library searching “easier” by re-casting our search question.

Here is an exotic fruit, what is it? 

Hard question – requires knowledge of all fruit

Trivial example: 

Here is an exotic fruit, is it an apple?

Easier question – requires knowledge of all apples

Fentanyl ClassifieR (prototype)
1) Build a highly curated 

library of JUST fentanyl 

analogs

2) Measure similarity 

between the query 

spectrum and the library 

spectra

3) Measure similarity 

between ALL of the 

fentanyl analog spectra in 

the library

4) Learn (e.g. cluster)

N

N O

a

b

c

d

e

a

(replib) Fentanyl

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

42

51

57

70

77

91

105

118

132

146

158

189

202

223

245

253 266 282 310 334

(swgdrug 3.3) Benztropine

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

42

55

67 77

83

96

110

124

140

152

165 201

216 244 307

(swgdrug 3.3) 1-Benzylpiperazine-d7

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

42

56

66

70

85

98

109 127

141

152 164

183

(mainlib) Cyclopentanone, 3-methyl-2-pentyl0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

41 55

69

83

98

110

123 137

153

168

(mainlib) Cyclohexanamine, 5-methyl-2-(1-methylethyl)-, (1α,2α,5β)-

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

41 56

70

81 98

112

140

155

(mainlib) Azacyclohex-3-en-5-one, 1-tert-butyl-3-methyl0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

41 57

70

82

86

95

110

124

152

167

(mainlib) Cyclohexane, 1,3,5-trimethyl0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

14

27

41

55

69

83 95

111

126

(mainlib) 3-Hexene, 3-methyl-, (E)-

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

15

27

41

55

69

83

91

98

(mainlib) 2-Propen-1-one, 1-cyclopropyl0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

27

41

55

69

81

96

(mainlib) Cyclobut-1-enylmethanol

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

27 39

55

65

83

(mainlib) 3-Oxatricyclo[4.1.1.0(2,4)]octane, 2,7,7-trimethyl0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

27

41

55

67

83

95

109

119

137

152

(mainlib) 1H-Benzocycloheptene, 2,4a,5,6,7,8,9,9a-octahydro-3,5,5-trimethyl-9-methylene0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

27

41

55

69 79

93

105

119

134

147

161

175

189 204

(mainlib) Phenanthrene, 7-ethenyl-1,2,3,4,4a,4b,5,6,7,8,10,10a-dodecahydro-4a,7-dimethyl-1-methylene-, [4aS-(4aα,4aβ,7β,10aβ)]-

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

15

29

41

55

67

79

91

105

119 131

145

157 171 186

199

213

227

241

256

(mainlib) Dibenzo[a,h]cyclotetradecene, 2,3,11,12-tetraethenyl-1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18-octadecahydro-, (2R*,3S*,4Z,9Z,11R*,1

0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

29

41

55

67

79 91

105

117 131 145

159

171 185

199

213 225 239 253 267 279 293 309 321 333

350

(mainlib) 1,5-Cycloundecadiene, 8,8-dimethyl-9-methylene0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340

0

50

100

27

41

55

67

79

93

107

121

134

147

161

175

190

Fentanyl ClassifieR (prototype)
1) Build a highly curated 

library of JUST fentanyl 

analogs

2) Measure similarity 

between the query 

spectrum and the library 

spectra

3) Measure similarity 

between ALL of the 

fentanyl analog spectra in 

the library

4) Learn (e.g. cluster)

Q

LA

LB

LC

LD

LE

LF

LG

LH

LD

LA

LH

LC

LE

LB

LF

LG

(1) Measure Similarity (2) Rank by Similarity

Traditional Library Searching

Fentanyl ClassifieR (prototype)
1) Build a highly curated 

library of JUST fentanyl 

analogs

2) Measure similarity 

between the query 

spectrum and the library 

spectra

3) Measure similarity 

between ALL of the 

fentanyl analog spectra in 

the library

4) Learn (e.g. cluster)

Q

LA

LB

LC

LD

LE

LF

LG

Q LA LB LC LD LE LF LG

sqa

sqb

1

sqc

sqd

sqe

sqf

sqg

1

sab

sac

sad

sae

saf

sag

sba

1

sbc

sbd

sbe

sbf

sbg

sca

scb

1

scd

sce

scf

scg

sda

sdb

sdc

1

sde

sdf

sdg

sea

seb

sec

sed

1

sef

seg

sfa

sfb

sfc

sfd

sfe

1

sfg

sga

sgb

sgc

sgd

sge

sgf

1

saq sbq

scq sdq seq

sgq sfq

Pre-computed

Fentanyl ClassifieR (prototype)
1) Build a highly curated 

library of JUST fentanyl 

analogs

2) Measure similarity 

between the query 

spectrum and the library 

spectra

3) Measure similarity 

between ALL of the 

fentanyl analog spectra in 

the library

4) Learn (e.g. cluster)

Q

LA

LB

LC

LD

LE

LF LG

Fentanyl ClassifieR (prototype)

N

N O

a

b

c

d

e

a

Fentanyl ClassifieR (prototype)

Compound hMF ΔΔmm Relatedness 

Index

Benzodioxole fentanyl – E 861 -44 0.42

3-Furanyl fentanyl – E 839 10 0.57

Cyclopentyl fentanyl – E 819 10 0.48

2-Furanyl fentanyl – E 816 10 0.51

Acryl fentanyl – E 775 50 0.25
N

N O

a

b

c

d

e

a

Fentanyl ClassifieR (prototype)

N

N

O
N

N O

a

b

c

d

e

a

Fentanyl ClassifieR (prototype)

Compound hMF ΔΔmm Relatedness 

Index

Benzodioxole fentanyl – E 861 -44 0.42

3-Furanyl fentanyl – E 839 10 0.57

Cyclopentyl fentanyl – E 819 10 0.48

2-Furanyl fentanyl – E 816 10 0.51

Acryl fentanyl – E 775 50 0.25

Compound hMF ΔΔmm Relatedness 

Index

Cyclopropyl fentanyl – E 274 2 0.02

Valeryl fentanyl – E 268 -14 0.02

Fentanyl 212 14 0.02

Cyclohexyl fentanyl – E 211 -40 0.01

Pivaloyl fentanyl – E 208 -14 0.01
N

N O

a

b

c

d

e

a

Fentanyl ClassifieR (prototype)

O

N

N O
N

N O

a

b

c

d

e

a

Fentanyl ClassifieR (prototype)

Compound hMF ΔΔmm Relatedness 

Index

Benzodioxole fentanyl – E 861 -44 0.42

3-Furanyl fentanyl – E 839 10 0.57

Cyclopentyl fentanyl – E 819 10 0.48

2-Furanyl fentanyl – E 816 10 0.51

Acryl fentanyl – E 775 50 0.25

Compound hMF ΔΔmm Relatedness 

Index

Cyclopropyl fentanyl – E 274 2 0.02

Valeryl fentanyl – E 268 -14 0.02

Fentanyl 212 14 0.02

Cyclohexyl fentanyl – E 211 -40 0.01

Pivaloyl fentanyl – E 208 -14 0.01

Compound hMF ΔΔmm Relatedness 

Index

m-fluoro fentanyl – D 908 14 0.56

p-fluoro fentanyl – D 890 14 0.56

o-fluoro fentanyl – D 856 14 0.47

isobutyryl fentanyl – E 806 18 0.38

butyryl fentanyl – E 796 18 0.37
N

N O

a

b

c

d

e

a

Fentanyl ClassifieR (prototype)

Compound hMF ΔΔmm Relatedness 

Index

Benzodioxole fentanyl – E 861 -44 0.42

3-Furanyl fentanyl – E 839 10 0.57

Cyclopentyl fentanyl – E 819 10 0.48

2-Furanyl fentanyl – E 816 10 0.51

Acryl fentanyl – E 775 50 0.25

Compound hMF ΔΔmm Relatedness 

Index

Cyclopropyl fentanyl – E 274 2 0.02

Valeryl fentanyl – E 268 -14 0.02

Fentanyl 212 14 0.02

Cyclohexyl fentanyl – E 211 -40 0.01

Pivaloyl fentanyl – E 208 -14 0.01

Compound hMF ΔΔmm Relatedness 

Index

m-fluoro fentanyl – D 908 14 0.56

p-fluoro fentanyl – D 890 14 0.56

o-fluoro fentanyl – D 856 14 0.47

isobutyryl fentanyl – E 806 18 0.38

butyryl fentanyl – E 796 18 0.37

O

N

N

F
Can we extend this to other classes of drugs?
Questions?

arun.moorthy@nist.gov

chemdata.nist.gov