Choline C 11 Injection

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Choline C 11 Injection is a sterile aqueous solution of choline chloride (C₄¹¹CH₁₄NOCl). It contains NLT 90% and NMT 110% of the labeled amount of [¹¹C] choline chloride expressed in MBq (or mCi)/mL at the time indicated in the labeling. It may contain buffering agents, preservatives, stabilizing agents, or sodium chloride. It may contain choline chloride carrier.

2 IDENTIFICATION

A. RADIONUCLIDIC IDENTITY

(See Radioactivity 〈821〉, Identification of Radionuclides, Half-Life Determination.) Acceptance criteria: The half-life of 11C is 19.4–21.4 min.

B. RADIOCHEMICAL IDENTITY: The retention time of choline C 11 from the radiochromatogram of the Sample solution is 90%–110% of the retention time of choline from the conductivity detector chromatogram of the Standard solution as determined in the Radiochemical Purity test.

3 ASSAY

RADIOACTIVE CONCENTRATION (STRENGTH)

(See Radioactivity 〈821〉, Assay of Radionuclides.)

Analysis: Using a dose calibrator or other suitable instrument for radiation measurements, measure the quantity of radioactivity in a known volume of the Injection. Determine the radioactive concentration, in MBq (or mCi)/mL.

Acceptance criteria: 90%–110% at the time indicated on the label

4 PURITY

4.1 RADIONUCLIDIC PURITY

(See Radioactivity 〈821〉, Identification of Radionuclides, Gamma-Ray Spectrometry.)

[NOTE—This may be a periodic quality indicator test. The Injection may be distributed and dispensed prior to completion of this test.] Analysis: Determine the purity of choline C 11 in the portion of Injection taken for the Radionuclidic Impurities test:

Result = [1 − (C_i/C_T)] × 100

C_i = sum of the concentrations of all longer-lived radionuclides, decay corrected to the expiration time from the Radionuclidic Impurities test (Bq/mL) or (µCi/mL)

C_T = sum of the concentrations of all long-lived radionuclides and choline C 11, all decay corrected to the expiration time from the Radionuclidic Impurities test (Bq/mL) or (µCi/mL)

Acceptance criteria: At the time of expiration, NLT 99.5% of radionuclides in the Injection correspond to 11C.

4.2 RADIOCHEMICAL PURITY

Mobile phase: 6 mM methanesulfonic acid. Alternatively, Mobile phase can be generated electrolytically using an automatic eluant generator. System suitability stock solution: 100 μg/mL each of USP Choline Chloride RS and 2-dimethylaminoethanol in 0.9% sodium chloride solution System suitability solution: 10 μg/mL each of USP Choline Chloride RS and 2-dimethylaminoethanol from System suitability stock solution in 0.9% sodium chloride solution

Standard stock solution: 100 μg/mL of USP Choline Chloride RS and 1.5 mg/mL of 2-dimethylaminoethanol in 0.9% sodium chloride solution Standard solution: 5 μg/mL of USP Choline Chloride RS and 75 μg/mL of 2-dimethylaminoethanol from Standard stock solution in 0.9% sodium chloride solution

Sample solution: Dilute a known volume of the Injection with an equal volume of water.

4.2.1 Chromatographic system

(See Positron Emission Tomography Drugs for Compounding, Investigational, and Research Uses 〈823〉, Facilities and Equipment, System Suitability for QC Equipment.)

Mode: LC

Detector: Conductivity with suppression and radiochemical detector in series Columns

Guard: 4.0-mm × 5-cm; 7-µm packing L77

Analytical: 4.0-mm × 25-cm; 7-µm packing L77

Temperatures Column: 30°

Conductivity detector: 30°

Flow rate: 1 mL/min Injection volume: 25 µL

Run time: NLT 3.5 times the retention time of choline

4.2.2 System suitability

Samples: System suitability solution and Standard solution

Suitability requirements: Use conductivity detector response for System suitability

Resolution: NLT 1.5 between 2-dimethylaminoethanol and choline, System suitability solution

Tailing factor: NMT 1.8 for choline, Standard solution

Relative standard deviation: NMT 1.0% for choline, Standard solution

4.2.3 Analysis

Sample: Sample solution

Measure the responses of all the peaks in the radiochromatogram. Calculate the percentage of choline C 11 in the portion of Injection taken:

Result = (r_U/r_T) × 100

r_U = response of choline C 11 in the radiochromatogram

r_T = sum of the responses of all peaks in the radiochromatogram

Acceptance criteria: NLT 95% of the total radioactivity is due to choline C 11.

5 IMPURITIES

5.1 RADIONUCLIDIC IMPURITIES

(See Radioactivity 〈821〉.)

[NOTE—The Injection may be distributed or dispensed prior to completion of the test.]

Sample: A suitable volume of Injection, decayed for a suitable length of time to eliminate interference due to 11C emissions

Analysis: Using a suitable gamma-ray spectrometer count an appropriate aliquot of the Sample for a period of time sufficient to collect a gamma spectrum. The resultant gamma spectrum should be analyzed for the presence of identifiable photopeaks, which are characteristic of radionuclidic impurities.

Determine the concentration of radionuclidic impurities in Bq (or µCi)/mL, decay corrected to the expiration time of the Injection:

Result = (C_i/C_T) × 100

C_i = sum of the concentrations of all longer-lived radionuclides, decay corrected to the expiration time (Bq/mL) or (µCi/mL)

C_T = sum of the concentrations of all long-lived radionuclides and choline C 11, all decay corrected to the expiration time (Bq/mL) or (µCi/mL)

Acceptance criteria: Total radionuclidic impurities are NMT 0.5% of the radioactivity of the Injection (see the Assay), decay corrected to the time of expiration.

5.2 RADIOCHEMICAL IMPURITIES

Analysis: From the radiochromatogram obtained in the Radiochemical Purity test, calculate the percentage of radiochemical impurities in the portion of Injection taken:

Result = (r_i/r_T) × 100

r_i = sum of areas of all the peaks other than choline C 11 in the radiochromatogram

r_T = sum of areas of all the peaks including the peak due to choline C 11 in the radio chromatogram

Acceptance criteria: NMT 5%

5.3 LIMIT OF 2-DIMETHYLAMINOETHANOL

Mobile phase, System suitability stock solution, System suitability solution, Standard solution, and Chromatographic system: Proceed as directed in the Radiochemical Purity test.

Sample solution: Use the Injection.

5.3.1 System suitability

Samples: System suitability solution and Standard solution

Suitability requirements: Use the conductivity detector response for both System suitability and Analysis. Resolution: NLT 1.5 between 2-dimethylaminoethanol and choline, System suitability solution

Tailing factor: NMT 1.8 for 2-dimethylaminoethanol, Standard solution

5.3.2 Analysis

Samples: Standard solution and Sample solution

Acceptance criteria: The conductivity detector response of 2-dimethylaminoethanol in the Sample solution is NMT that of the Standard solution.

5.4 LIMIT OF ETHANOL

[NOTE—Perform this test if Ethanol is known to be present in the article. This may be a periodic quality indicator test. The Injection may be distributed and dispensed prior to completion of this test.]

Standard stock solution: 5 mg/mL of ethanol prepared as follows. Transfer 0.3 mL of USP Alcohol Determination±Alcohol RS to a 10-mL volumetric flask. Dilute with water to volume.

Standard solution: Transfer 1 mL of Standard stock solution and 4 mL of water to a suitable flask to obtain 5 mL. Sample solution: Transfer 1 mL of the Injection and 4 mL of water to suitable flask to obtain 5 mL.

Chromatographic system (See Positron Emission Tomography Drugs for Compounding, Investigational, and Research Uses 〈823〉, Facilities and Equipment, System Suitability for QC Equipment.)

Mode: GC

Detector: Flame ionization

Column: 0.53-mm × 30-m fused-silica; coated with a 1-µm film of phase G16 Temperatures

Injection port: 250°

Detector: 300° Column: See Table 1.

Table 1

Carrier gas: Helium

Flow rate: 5 mL/min

Injection volume: 0.5 µL

Injection type: Split, Split ratio 10:1

5.4.1 System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 2%

5.4.2 Analysis

Samples: Standard solution and Sample solution

Acceptance criteria: The response for ethanol from the Sample solution is NMT the response of ethanol in the Standard solution.

6 SPECIFIC TESTS

6.1 SPECIFIC ACTIVITY

From the conductivity detector chromatogram obtained in the Radiochemical Purity test, calculate the concentration of choline (C ) in the portion of the Injection taken:

C = (r_U/r_S) × C_S

r_U = conductivity detector response of choline in the Sample solution

r_S = conductivity detector response of choline in the Standard solution

C_S = concentration of USP Choline Chloride RS in the Standard solution (μg/mL)

[NOTE—mCi/μmol is the same as Ci/mmol.]

Calculate the specific activity in MBq (mCi)/μmol:

Result = (A × B)/C_U

A  = radioactive concentration determined at the end of synthesis (mCi/mL)

B = molecular weight of choline, 139.62 (µg/µmol)

C_U = concentration of choline in the Sample solution calculated in the previous equation (μg/mL)

Acceptance criteria: NLT 55,500 MBq (1500 mCi)/μmol

6.2 pH

Analysis: Place a suitable volume of the Injection on pH indicator paper, short-range. Acceptance criteria: 4.5–7.5

6.3 BACTERIAL ENDOTOXINS TEST 〈85〉

Meets the requirements

6.4 STERILITY TESTS 〈71〉

[NOTE—The Injection may be distributed or dispensed prior to completion of the test, the latter test being started within 30 h of final manufacture.]

Sample: Use 0.1–0.3 mL of Injection

Acceptance criteria: Meets the requirements

6.5 APPEARANCE

Clear, colorless solution, free of foreign particulates

7 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in single-dose or multiple-dose containers that are adequately shielded. Store at controlled room temperature.

LABELING: The label indicates the time and date of calibration; the concentration of choline C 11 expressed in MBq (mCi)/mL, at the time of calibration; the expiration time and date; the name and quantity of any added preservative or stabilizer. Calculate the correct dosage from date and time of calibration. The labeling indicates that in making dosage calculations, correction is to be made for radioactive decay. The radioactive half-life of 11C is 20.4 min. The label also indicates the following:

[CAUTION—Radioactive Material. Do not use if cloudy or if it contains visible particulate matter.]

USP REFERENCE STANDARDS 〈11〉

USP Alcohol Determination±Alcohol RS

USP Choline Chloride RS (USP 1-Dec-2021)