[11C]NNC 112 FOR INJECTION: PRECURSOR AND REFERENCE
COMPOUND − ACCEPTANCE TESTING AND FORMS
PET Radiopharmaceutical Sciences Section,
Molecular Imaging Branch,
National Institute of Mental Health,
National Institutes of Health,
Bldg. 10, Rm. B3 C338,
Bethesda, MD 20892
Date of review: 0603/04
1. Overview
The production of [11C]NNC 112 for Injection requires the use of desmethyl-NNC 112 ((+)- 5benzofuran-4-yl-8-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ol)
methylation.
as
a
precursor
for
11C-
The SOP for acceptance testing of desmethyl-NNC 112 is described below.
Acceptance testing is required to validate the chemical identity and chemical purity of desmethyl-NNC
112. Upon acceptance desmethyl-NNC 112 may be released for the production of [ 11C]NNC 112 for
Injection. Upon release, the desmethyl-NNC 112 is to be tested annually thereafter for chemical
purity (via HPLC, section 3.1) and chemical identity (via LC-MS, section 3.2). This SOP also contains
testing methods and acceptance criteria for a standard sample of NNC 112 (section 5). This nonradioactive material is also utilized in QC for the determination of the specific radioactivity and
chemical identity of [11C]NNC 112 for Injection.
2. Acceptance criteria for precursor and reference compound
(A) Precursor
Source: the precursor, desmethyl-NNC 112, is obtained from Christer Halldin, Ph.D. at Karolinska
Institute. Dept. of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, Stockholm,
Sweden.
The acceptance criteria for precursor are as follows:

1H-NMR

LC-MS of desmethyl-NNC 112 performed in the PRSS on the Finnigan LCQDeca LC-MS
spectrum of desmethyl-NNC 112 from this laboratory to verify chemical structure.
(ThermoQuest, Germany) to confirm chemical structure and purity

HPLC in the PRSS showing the chemical purity of precursor to be ≥ 90%.
(B) Reference compound
Source: the reference compound, NNC 112, is obtained from Christer Halldin, Ph.D. at Karolinska
Institute, Dept. of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, Stockholm,
Sweden.
The acceptance criteria for reference compound are as follows:

1H-NMR

LC-MS of NNC 112 performed in the PRSS on the Finnigan LCQDeca LC/MS (ThermoQuest,
spectrum of NNC 112 from this laboratory to verify chemical structure.
Germany) to confirm chemical structure and purity

HPLC in the PRSS showing the chemical purity of NNC 112 to be ≥ 90%.
Document 7. [11C]NNC112 for Injection: Precursor and Reference Compound − Acceptance Testing and Form
Page 1 of 7
[11C]NNC 112 FOR INJECTION: PRECURSOR AND REFERENCE
COMPOUND − ACCEPTANCE TESTING AND FORMS
PET Radiopharmaceutical Sciences Section,
Molecular Imaging Branch,
National Institute of Mental Health,
National Institutes of Health,
Bldg. 10, Rm. B3 C338,
Bethesda, MD 20892
Date of review: 0603/04
3. Precursor and reference compounds acceptance forms
Approved by: __________________________ Initials___________
Date:__________
Victor W Pike, Ph.D., Chief, PET Radiopharmaceutical Sciences, NIMH
Precursor Compound Acceptance Form
Receipt of compound:
Compound name: Desmethyl-NNC 112
Lot #
Supplier Name: Christer Halldin, Ph.D.
Received by:
Karolinska Institute. Dept. of Clinical
Neuroscience, Psychiatry Section, Karolinska
Hospital, Stockholm, Sweden.
Date received:
Quantity:
Molecular formula: C18H16ClNO2
Molecular weight: 313.7788
1
H-NMR spectrum
Record weight of desmethyl-NNC 112 _________ dissolved in ca 0.8 mL of 0.03% TMS (v/v) in CDCl3
Proton assignment
Benzyl-H
Aromatic protons
Expected chemical shift
(ppm)
Observed
chemical
shift
(ppm)
Acceptance?
4.68 (d, 1H)
Yes or No
7.62 (d, 1-H, furyl-H), 7.54 (d, benzoH,1H), 7.28 (Solvent, CDCl3), 7.22 (t,
Yes or No
1 H, benzo-H), , 7.15 (s, 1 H, benzoH), 6.96 (d, 1H, benzo-H), 6.89 (d,
1H, furyl-H), 6.45 (s, 1H, benzo-H)
HPLC
Record weight _____________ mg in 10 mL of 50: 50 ethanol-saline.
Column: Luna C-18; 10 m; 4.6 x 250 mm; Phenomenex; Part # 00G-4094-EO,
Document 7. [11C]NNC112 for Injection: Precursor and Reference Compound − Acceptance Testing and Form
Page 2 of 7
[11C]NNC 112 FOR INJECTION: PRECURSOR AND REFERENCE
COMPOUND − ACCEPTANCE TESTING AND FORMS
PET Radiopharmaceutical Sciences Section,
Molecular Imaging Branch,
National Institute of Mental Health,
National Institutes of Health,
Bldg. 10, Rm. B3 C338,
Bethesda, MD 20892
Date of review: 0603/04
Record serial # of this column: __________
Criterion
Acceptance?
Date
(circle one)
Retention time 3.3 1.0 min
Yes or No
Peak area ≥ 90 %
Yes or No
LC/MS
Criterion
Observed ion
Acceptance
(expected
(circle one)?
+
m/z = [M+1] )
m/z = [M+1]
+
314.1
Yes or No
316.1 (37Cl isotope)
Yes or No
Attached documents, acceptance criteria and test results:
1.
1H-NMR
2.
LC-MS data from this laboratory?
YES_________ NO__________.
3.
HPLC chromatogram from this laboratory?
YES_________ NO__________.
spectrum from this laboratory?
YES_________ NO__________.
(An example of a set of satisfactory attached documents is included in Document 9: Validation Runs).
Chemical structure:
Acceptance criteria:
Cl
1. Identity: confirmed by 1H-NMR and LC-MS
NH
HO
2. Purity: ≥ 90 % by HPLC
3. Identity: confirmed by LC/MS
O
Document 7. [11C]NNC112 for Injection: Precursor and Reference Compound − Acceptance Testing and Form
Page 3 of 7
[11C]NNC 112 FOR INJECTION: PRECURSOR AND REFERENCE
COMPOUND − ACCEPTANCE TESTING AND FORMS
PET Radiopharmaceutical Sciences Section,
Molecular Imaging Branch,
National Institute of Mental Health,
National Institutes of Health,
Bldg. 10, Rm. B3 C338,
Bethesda, MD 20892
Date of review: 0603/04
Test Results
Test
Results
Procedure
1. NMR ( This laboratory)
SOP # QA308(2.1)
2. LC-MS (This laboratory)
SOP # QA308(2.3)
3. HPLC (This laboratory)
SOP # QA308(2.2)
Checked by:
Accepted by:
Storage condition:
Date
Date
Initials
Document 7. [11C]NNC112 for Injection: Precursor and Reference Compound − Acceptance Testing and Form
Page 4 of 7
[11C]NNC 112 FOR INJECTION: PRECURSOR AND REFERENCE
COMPOUND − ACCEPTANCE TESTING AND FORMS
PET Radiopharmaceutical Sciences Section,
Molecular Imaging Branch,
National Institute of Mental Health,
National Institutes of Health,
Bldg. 10, Rm. B3 C338,
Bethesda, MD 20892
Date of review: 0603/04
NNC 112 Reference Compound Acceptance Form
Approved by: __________________________ Initials___________
Date:__________
Victor W Pike, Ph.D., Chief, PET Radiopharmaceutical Sciences, NIMH
Receipt of compound:
Compound name: Desmethyl-NNC 112
Lot #
Supplier Name: Christer Halldin, Ph.D.
Received by:
Karolinska Institute. Dept. of Clinical
Neuroscience, Psychiatry Section, Karolinska
Hospital, Stockholm, Sweden.
Date received:
Quantity:
Molecular formula: C19H18ClNO2
Molecular weight: 327.8047
1
H-NMR spectrum
Record the weight __________of NNC 112 dissolved in ca 0.8 mL of 0.03% TMS (v/v) in CDCl3
Proton
Expected chemical shift
Observed
assignment
(ppm)
chemical
Acceptance?
shift
(ppm)
Benzyl-H
4.77 (d, 1H)
Yes or No
-NCH3
2.39 (s, 3H)
Yes or No
Aromatic protons
7.60 (d, 1-H, furyl-H), 7.58 (dd, benzo-
Yes or No
H,1H), 7.28 (Solvent, CDCl3), 7.24 (t, 1
H, benzo-H), 7.14 (s, 1 H, benzo-H),
7.07 (d, 1H, benzo-H), 6.82 (d, 1H, furylH), 6.23 (s, 1H, benzo-H)
Document 7. [11C]NNC112 for Injection: Precursor and Reference Compound − Acceptance Testing and Form
Page 5 of 7
[11C]NNC 112 FOR INJECTION: PRECURSOR AND REFERENCE
COMPOUND − ACCEPTANCE TESTING AND FORMS
PET Radiopharmaceutical Sciences Section,
Molecular Imaging Branch,
National Institute of Mental Health,
National Institutes of Health,
Bldg. 10, Rm. B3 C338,
Bethesda, MD 20892
Date of review: 0603/04
HPLC
Record weight of reference compound _____ mg in 10 mL of 50:50 USP grade ethanol-saline.
Column: Luna C-18; 10 m; 4.6 x 250 mm; Phenomenex Part # 00G-4094-EO.
Record Serial # of this column: __________
Criterion
Acceptance?
Date
(circle one)
Retention time 6.4 1.0 min
Yes or No
Peak area > 90%
Yes or No
LC-MS
Criterion
Observed ion
Acceptance
(expected
(circle one)?
+
m/z = [M+1] )
m/z = [M+1]
+
328.1
330.1
Yes or No
(37Cl
isotope)
Yes or No
Attached documents, acceptance criteria and test results:
1.
1H-NMR
2.
LC-MS data from this laboratory?
YES_________ NO__________.
3.
HPLC chromatogram from this laboratory?
YES_________ NO__________.
spectrum from this laboratory attached?
YES_________ NO__________.
(An example of a set of satisfactory attached documents is included in Document 9: Validation Runs).
Chemical structure:
Acceptance criteria:
Cl
1. Identity: confirmed by 1H-NMR
N
HO
CH3
2. Purity: ≥ 90 % by HPLC
3. Identity: confirmed by LC-MS
O
Document 7. [11C]NNC112 for Injection: Precursor and Reference Compound − Acceptance Testing and Form
Page 6 of 7
[11C]NNC 112 FOR INJECTION: PRECURSOR AND REFERENCE
COMPOUND − ACCEPTANCE TESTING AND FORMS
PET Radiopharmaceutical Sciences Section,
Molecular Imaging Branch,
National Institute of Mental Health,
National Institutes of Health,
Bldg. 10, Rm. B3 C338,
Bethesda, MD 20892
Date of review: 0603/04
Test Results
Test
Results
Procedure
1. NMR ( This laboratory)
SOP # QA308(3.1)
2. LC-MS (This laboratory)
SOP # QA308(3.3)
3. HPLC (This laboratory)
SOP # QA308(3.2)
Checked by:
Accepted by:
Storage condition:
Date
Date
Initials
Chemist_____________________________Initials_________________Date________________
Document 7. [11C]NNC112 for Injection: Precursor and Reference Compound − Acceptance Testing and Form
Page 7 of 7