Fludeoxyglucose F 18 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

Fludeoxyglucose F 18 Injection is a sterile, aqueous solution of fludeoxyglucose F 18. The chemical name of fludeoxyglucose F 18 is 2-deoxy 2-[¹⁸F]uoro-d-glucose (also known as 2-deoxy-2-uoro-[¹⁸F]-d-glucopyranose). (USP 1-May-2024) It contains NLT 90% and NMT 110% of the labeled amount of fludeoxyglucose F 18 (C₆H₁₁¹⁸FO₅) (USP 1-May-2024) 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 does not contain any added carrier.

2 IDENTIFICATION

A. Radionuclidic Identity

(See Radioactivity 〈821〉, 5. Identication of Radionuclides, 5.1 Half-Life Determination)

Acceptance criteria: The half-life is 105–115 min.

B. Radiochemical Identity

Spray reagent: 10 mg/mL of p-anisidine in a mixture of methanol and butanol (10:90)

Procedure: After completing the Analysis in the test for Radiochemical Purity, spray the TLC strip with Spray reagent and heat strip on a hot plate until the spot for USP Fludeoxyglucose RS is visible.

Acceptance criteria: The R_F value of fludeoxyglucose F 18 in the Sample solution is 90%–110% of the R_F value of USP Fludeoxyglucose RS in the Standard solution as determined in the test for Radiochemical Purity.

3 ASSAY

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Radioactive Concentration (Strength)

(See Radioactivity 〈821〉, 6. 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 radioactivity, in MBq (or mCi)/mL.

Acceptance criteria: 90%–110% (USP 1-May-2024) at the time indicated on the label

4 PURITY

4.1 Radionuclidic Purity

(See Radioactivity 〈821〉, 5. Identication of Radionuclides, 5.2 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 fludeoxyglucose F 18 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 fludeoxyglucose F 18, 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 corresponds to 18F. Change to read:

4.2 Radiochemical Purity

(USP 1-May-2024)

Standard solution: 5 (USP 1-May-2024) mg/mL of USP Fludeoxyglucose RS in water (USP 1-May-2024)

Sample solution: A volume of Injection, appropriately diluted with water (USP 1-May-2024) to a concentration of 18.5–111 (USP 1-May-2024) MBq/mL (0.5–3 (USP 1-May-2024) mCi/mL) or to a concentration suitable for the detector to be used

4.2.1 Chromatographic system

Mode: TLC

Adsorbent: 0.2 or 0.25 (USP 1-May-2024) -mm layer of chromatographic silica gel strip

Application volume: 0.5 µL

Developing solvent system: Acetonitrile and water (95:5) (USP 1-May-2024)

4.2.2 Analysis

Samples: Standard solution and Sample solution

Develop the chromatogram in the Developing solvent system until the solvent has moved about 90% of the length of the strip. Remove the strip and allow to dry in the air or under a stream of a compressed gas such as nitrogen or air. Determine the radioactivity distribution by scanning the chromatogram with a suitable collimated radiation detector. After completing the test for Radiochemical Purity, use the TLC strip for the Radiochemical Identity test.

Calculate the percentage of fludeoxyglucose F 18 (C₆H₁₁¹⁸FO₅) _{(USP 1-May-2024)} in the portion of Injection taken:

Result = (r_U /r_T ) × 100

r_U = area of the peak due to fludeoxyglucose F 18 in the radio-TLC chromatogram

r_T = sum of areas of all the peaks including the peak due to fludeoxyglucose F 18 in the radio-TLC chromatogram

Acceptance criteria: NLT 90% of the total radioactivity is due to fludeoxyglucose F 18

5 IMPURITIES

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5.1 Radionuclidic Impurities

[Note—This may be a periodic quality indicator test. The Injection may be distributed or dispensed prior to completion of the test.] Sample solution: (USP 1-May-2024) A suitable volume of Injection, decayed for a suitable length of time to eliminate interference due to 18F emissions

Analysis: Using a suitable gamma-ray spectrometer count an appropriate aliquot of the Sample solution (USP 1-May-2024) 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) i

C_T = sum of the concentrations of all long-lived radionuclides and fludeoxyglucose F 18, 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 radio-TLC chromatogram obtained in the Radiochemical Purity test, calculate the 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 fludeoxyglucose F 18 in the radio-TLC chromatogram

r_T = sum of areas of all the peaks including the peak due to fludeoxyglucose F 18 in the radio-TLC chromatogram 

Acceptance criteria: NMT 10%

5.3 Limit of Fludeoxyglucose Related Compound A

[Note—Perform this test if fludeoxyglucose related compound A (also known as aminopolyether) is used in the synthesis of fludeoxyglucose F 18.]

Adsorbent: Aluminum oxide strips

Standard solution: 50 µg/mL of USP Fludeoxyglucose Related Compound A RS in saline TS

Sample solution: Use the Injection.

Application volume: 4 µL

Analysis

Samples: Standard solution and Sample solution

Spot the Standard solution and Sample solution on the strip. Allow to dry and place the strip in a chamber containing fresh iodine crystals. Develop the plate until a spot is visible on the strip for the Standard solution.

Acceptance criteria: The size and intensity of the spot from the Sample solution is NMT that from the Standard solution.

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5.4 Limit of Fludeoxyglucose Related Compound B

[Note—This may be a periodic quality indicator test. Perform this test if fludeoxyglucose related compound B is a potential process impurity in the synthesis of fludeoxyglucose F 18. The Injection may be distributed or dispensed prior to completion of the test.] Mobile phase: 0.1 M sodium hydroxide

System suitability solution: 0.01 mg/mL each of USP Fludeoxyglucose RS and USP Fludeoxyglucose Related Compound B RS in water Standard solution: 0.01 mg/mL of USP Fludeoxyglucose Related Compound B RS in water

Sample solution: Use the Injection.

5.4.1 Chromatographic system

(See Positron Emission Tomography Drugs for Compounding, Investigational, and Research Uses 〈823〉, 4. Facilities and Equipment, 4.5 System Suitability for QC Equipment. (USP 1-May-2024) )

Mode: LC

Detector: Pulsed amperometric detector with suitable pulse sequence

Columns

Guard: 4.0-mm × 5-cm; 10-µm packing L46

Analytical: 4.0-mm × 25-cm; 10-µm packing L46

Flow rate: 0.4 mL/min

Injection volume: 10 µL

Run time: NLT 1.5 times the retention time (USP 1-May-2024) of fludeoxyglucose

5.4.2 System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.0 between fludeoxyglucose and fludeoxyglucose related compound B, System suitability solution

Tailing factor: NMT 1.5, Standard solution

Signal-to-noise ratio: NLT 50, Standard solution

5.4.3 Analysis

Samples: Standard solution and Sample solution

(USP 1-May-2024)

Calculate the amount of fludeoxyglucose related compound B in the portion of Injection taken:

Result = (r_U /r_S ) × C_S

r_U = peak area of fludeoxyglucose related compound B from the Sample solution

r_S = peak area of fludeoxyglucose related compound B (USP 1-May-2024) from the Standard solution

C_S = concentration of USP Fludeoxyglucose Related Compound B RS in the Standard solution (mg/mL)

Acceptance criteria: NMT 1.0 mg/V of fludeoxyglucose related compound B is found, where V is the volume (mL) of dose injected Change to read:

5.5 Limit of Acetonitrile and Ethanol

[Note—Perform this test if Ethanol and acetonitrile are known to be present in the article.]

Standard solution: 0.04% (v/v) acetonitrile and 0.5% (v/v) ethanol from USP Alcohol Determination±Alcohol RS in water Sample solution: Use the Injection. [Note—Injection may be appropriately diluted with water (USP 1-May-2024) if necessary.]

5.5.1 Chromatographic system

Mode: GC

Detector: Flame ionization

Column: 0.53-mm × 30-m fused-silica; coated with a 1.0–1.2-µm lm of phase G16

Temperatures

Injection port: 150°

Detector: 250°

Column: See Table 1.

Table 1

Carrier gas: Helium

[Note—Nitrogen may be used as a makeup gas.]

Flow rate: 9 mL/min

Injection volume: 1 µL

Injection type: Splitless injector system

5.5.2 System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 7.0 between acetonitrile and ethanol

Relative standard deviation: NMT 5.0%

5.5.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentages of acetonitrile and ethanol in the Injection:

Result = (r_U /r_S ) × C_S

r_U = peak response of acetonitrile or ethanol from the Sample solution (USP 1-May-2024)

r_S = peak response of acetonitrile or ethanol from the Standard solution

C_S = percentage of the acetonitrile or ethanol in the Standard solution

Acceptance criteria: NMT 0.041% of acetonitrile _{(USP 1-May-2024)} ; NMT 0.5% of ethanol _{(USP 1-May-2024)}

6 SPECIFIC TESTS

Appearance: Clear, colorless solution, free from visible particulates

pH

Analysis: Apply a suitable volume of the Injection on a suitable short-range pH indicator paper.

Acceptance criteria: 4.5–7.5

Bacterial Endotoxins Test 〈85〉: Meets the requirements

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Sterility Tests 〈71〉: The Injection may be distributed or dispensed prior to completion of the test, which must be started within 30 h after completion of production. (USP 1-May-2024)

Sample: Use NLT 0.25 mL of the Injection.

Acceptance criteria: Meets the requirements

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose or multiple-dose containers that are adequately shielded. Store at controlled room temperature. Change to read:

Labeling: The label indicates the time and date of calibration; the radioactivity concentration of fludeoxyglucose F 18 expressed in MBq (or mCi)/mL at the time of calibration; the total volume or total radioactivity at the time of calibration; (USP 1-May-2024) the expiration time and date; and the name and quantity of any added preservative or stabilizer. The labeling indicates that in making dosage calculations, correction is to be made for radioactive decay. The radioactive half-life of 18F is 109.7 min. (USP 1-May-2024) The label also indicates the following:

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

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USP Reference Standards 〈11〉

USP Alcohol Determination±Alcohol RS

USP Fludeoxyglucose RS

2-Deoxy-2-uoro-d-glucose.

C₆H₁₁FO₅                  182.15 _{(USP 1-May-2024)}

USP Fludeoxyglucose Related Compound A RS

4,7,13,16,21,24-Hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane.

C₁₈H₃₆N₂O₆              376.49

USP Fludeoxyglucose Related Compound B RS

2-Chloro-2-deoxy-d-glucose.

C₆H₁₁ClO₅              198.60