Pamidronate Disodium for 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

Pamidronate Disodium for Injection (USP 1-May-2023) contains an amount of Pamidronate Disodium equivalent to (USP 1-May-2023) NLT 93.0% and NMT 108.0% of the labeled amount of pamidronate disodium (C₃H₉NNa₂O₇P₂).

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

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3.1 PROCEDURE

Mobile phase: 0.47 mL of formic acid, anhydrous in 2500 mL of water. Adjust with a 2 N sodium hydroxide solution to a pH of 3.5. [NOTE-The small amounts of formic acid have a strong influence on the retention times.]

Standard solution: 2.5 mg/mL of USP Pamidronate Disodium RS in water. [NOTE-Calculate the concentration, C, of anhydrous pamidronate disodium, the molecular weights of anhydrous and pentahydrate pamidronate disodium being 279.06 and 369.11, respectively.]

Sample solution: Nominally 2 mg/mL of anhydrous pamidronate disodium prepared by reconstituting and combining a suitable number of vials of Pamidronate Disodium for Injection in water

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: Refractive index

Column: 4.6-mm x 10-cm; 12-µm (USP 1-May-2023) packing L23. [NOTE-It is required to saturate new columns for at least 12 h before starting analysis.] (USP 1-MAY-2023)

Column temperature: 35°

Flow rate: 14 (USP 1-May-2023) mL/min

Injection volume: 100 µL

Run time: NLT 2.5 times the retention time of pamidronate (USP 1-May-2023)

3.3 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: 0.3-1.2

Relative standard deviation: NMT 2.0%

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of pamidronate disodium (C₃H₉NNa₂O₇P₂) in the portion of Pamidronate Disodium for Injection taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of pamidronate from the Sample solution

r_S = peak response of pamidronate from the Standard solution

C_S = concentration of anhydrous USP Pamidronate Disodium RS in the Standard solution (mg/mL)

C_U = nominal concentration of anhydrous pamidronate disodium in the Sample solution (mg/mL)

Acceptance criteria: 93.0%-108.0%

4 PERFORMANCE TESTS

UNIFORMITY OF DOSAGE UNITS (905), Weight Variation: Meets the requirements

5 IMPURITIES

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LIMIT OF BETA ALANINE

Buffer 1: 13.6 g/L of monobasic potassium phosphate and 5.6 g/L of sodium 1-hexanesulfonate in water. Adjust with phosphoric acid to a pH of 2.5.

Buffer 2: 27.2 g/L of monobasic potassium phosphate and 2% phosphoric acid solution in water

Mobile phase: Acetonitrile and Buffer 1 (5:95)

Diluent: Acetonitrile and Buffer 2 (5:95)

Standard solution: 0.01 mg/mL of USP Beta Alanine RS in Diluent

Sample stock solution: Nominally 9 mg/mL of pamidronate disodium from Pamidronate Disodium for Injection prepared as follows. Reconstitute NLT 1 vial with a suitable amount of water and shake to mix.

Sample solution: Nominally 5 mg/mL of pamidronate disodium from the Sample stock solution in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm x 25-cm; 5-µm packing L1

Temperature: 40°

Flow rate: 1 mL/min

Injection volume: 100 µL

Run time: NLT 2 times the retention time of beta alanine

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 5.0%

Signal-to-noise ratio: NLT 10

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of beta alanine in the portion of Pamidronate Disodium for Injection taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of beta alanine from the Sample solution

r_S = peak response of beta alanine from the Standard solution

C_S = concentration of USP Beta Alanine RS in the Standard solution (mg/mL)

C_U = nominal concentration of pamidronate disodium in the Sample solution (mg/mL) (USP 1-May-2023)

Acceptance criteria: NMT 0.25%

6 SPECIFIC TESTS

6.1 PH (791)

Sample solution: Use the solution constituted as directed in the labeling.

Acceptance criteria: 6.0-7.0

6.2 WATER DETERMINATION (921), Method I, Method la

NMT 5%

6.3 CONSTITUTED SOLUTION

At the time of use, it meets the requirements for Injections and Implanted Drug Products (1), Product Quality Tests Common to Parenteral Dosage Forms, Specific Tests, Completeness and Clarity of Solutions.

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6.4 PARTICULATE MATTER IN INJECTIONS (788)

Sample solution: Use solution constituted as directed in the labeling. (USP 1-May-2023)

Acceptance criteria: Meets the requirements for small-volume injections

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6.5 BACTERIAL ENDOTOXINS TEST (85)

Meets the requirements (USP 1-May-2023)

6.6 STERILITY TESTS (71)

Meets the requirements

6.7 OTHER REQUIREMENTS

It meets the requirements under Labeling (7), Labels and Labeling for Injectable Products.

7 ADDITIONAL REQUIREMENTS

7.1 PACKAGING AND STORAGE

Preserve as described under Packaging and Storage Requirements (659), Injection Packaging, Packaging for Constitution. Store at controlled room temperature.

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7.2 USP REFERENCE STANDARDS (11)

USP Beta Alanine RS

3-Aminopropanoic (USP 1-May-2023) acid.

C₃H₇NO₂ 89.09(USP 1-May-2023)

USP Pamidronate Disodium RS