Etidronate Disodium Tablets

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

Etidronate Disodium Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of etidronate disodium (C₂H₆Na₂O₇P₂).

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197A or 197M (CN 1-May-2020)

Standard: Recrystallize USP Etidronate Disodium RS from water and dry it at 105° for 1 h.

Sample: Recrystallize the sample from water and dry it at 105° for 1 h.

Analysis and Acceptance criteria for 〈197M〉: (CN 1-May-2020) The spectra of trifluorovinyl chloride polymer and Mineral oil dispersions of the Sample, separately prepared, exhibit maxima in the regions of 4000–1350 cm−1 and 1350–450 cm−1, respectively, only at the same wavelengths as those of similar preparations of the Standard. (CN 1-May-2020)

B. 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

Procedure

Mobile phase: 35–40 mM ammonium nitrate solution in water. Adjust with dilute ammonium hydroxide to a pH of 7.0.

Standard solution: 0.73–0.75 mg/mL of USP Etidronic Acid Monohydrate RS in 1 N sodium hydroxide VS and Mobile phase (1:150)

Sample solution: Transfer a quantity of finely powdered Tablets (NLT 20), nominally equivalent to 160–170 mg of etidronate disodium, to a 200-mL volumetric flask, and dilute with Mobile phase to volume. Agitate the solution for at least 5 min, and pass through a nylon fllter of 0.45-μm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: Refractive index

Column: 4.6-mm × 15-cm; 10-μm packing L23

Temperatures

Detector: 32°

Column: 32°

Flow rate: 1.5 mL/min

Injection volume: 20 μL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 1.5%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of etidronate disodium (C₂H₆Na₂O₇P₂) in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Etidronic Acid Monohydrate RS in the Standard solution (mg/mL)

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

M_r1 = molecular weight of etidronate disodium, 249.99

M_r2 = molecular weight of etidronic acid monohydrate, 224.04

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: Water; 900 mL

Apparatus 1: 100 rpm

Time: 30 min

Mobile phase: Prepare as directed in the Assay.

Standard solution

For products labeled to contain 200 mg of etidronate disodium: Transfer 20 mg of USP Etidronic Acid Monohydrate RS to a 100-mL volumetric flask, dissolve in 50 mL of water, add 2.0 mL of 0.1 N sodium hydroxide VS, and dilute with water to volume.

For products labeled to contain 400 mg of etidronate disodium: Transfer 20 mg of USP Etidronic Acid Monohydrate RS to a 50-mL volumetric flask, dissolve in 25 mL of water, add 2.0 mL of 0.1 N sodium hydroxide VS, and dilute with water to volume.

Sample solution: Transfer a portion of the solution under test to an HPLC vial.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: Refractive index

Column: 4.6-mm × 15-cm; 10-μm packing L23

Temperatures

Detector: 32°

Column: 32°

Flow rate: 1.5 mL/min

Injection volume: See Table 1.

Table 1

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 1.5%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of etidronate disodium (C₂H₆Na₂O₇P₂) dissolved:

Result = (r_U/r_S) × C_S × V × (M_r1/M_r2) × (1/L) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Etidronic Acid Monohydrate RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

M_r1 = molecular weight of etidronate disodium, 249.99

M_r2 = molecular weight of etidronic acid monohydrate, 224.04

L = label claim (mg/Tablet)

Tolerances: NLT 70% (Q) of the labeled amount of etidronate disodium (C₂H₆Na₂O₇P₂) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Limit of Phosphite and Phosphate

Mobile phase: 20 mM ammonium nitrate solution in water. Adjust with dilute ammonium hydroxide to a pH of 7.0.

Standard solution: A mixture of 0.04 mg/mL of dibasic sodium phosphite, on the anhydrous basis from USP Etidronate Disodium Related Compound A RS, and anhydrous dibasic sodium phosphate in Mobile phase

Sample solution: Nominally equivalent to 4.0 mg/mL of etidronate disodium in Mobile phase prepared as follows. Transfer a quantity of finely powdered Tablets (NLT 20), equivalent to 200 mg of etidronate disodium, to a 50-mL volumetric flask. Add about 40 mL of Mobile phase, dissolved by sonication, and dilute with Mobile phase to volume. Centrifuge a portion and use the clear supernatant.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: Refractive index

Column: 4.6-mm × 15-cm; 10-μm packing L23

Column temperature: 35°

Flow rate: 1.5 mL/min

Injection volume: 100 μL

System suitability

Sample: Standard solution

[Note—The typical relative retention times are about 0.7 for the phosphate, relative to the phosphite, and 1.0 for the phosphite.]

Suitability requirements

Resolution: NLT 1.5 between the phosphite and phosphate peaks

Relative standard deviation: NMT 5% for both the phosphite and phosphate peaks

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of phosphite, determined as monobasic sodium phosphite, in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 100

r_U = peak response of phosphite from the Sample solution

r_S = peak response of phosphite from the Standard solution

C_S = concentration of USP Etidronate Disodium Related Compound A RS on the anhydrous basis in the Standard solution (mg/mL)

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

M_r1 = molecular weight of monobasic sodium phosphite, 103.98

M_r2 = molecular weight of dibasic sodium phosphite, 125.96

Calculate the percentage of phosphate, determined as dibasic sodium phosphate, in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of phosphate from the Sample solution

r_S = peak response of phosphate from the Standard solution

C_S = concentration of dibasic sodium phosphate in the Standard solution (mg/mL)

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

Acceptance criteria

Phosphite: NMT 1.0%, determined as monobasic sodium phosphite

Phosphate: NMT 1.0%, determined as dibasic sodium phosphate

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Etidronate Disodium RS

USP Etidronate Disodium Related Compound A RS

Sodium phosphite dibasic pentahydrate.

Na₂HPO₃ · 5H₂O 216.04

USP Etidronic Acid Monohydrate RS

Phosphonic acid, (1-hydroxyethylidene)bis-, monohydrate

C₂H₈O₇P₂ · H₂O 224.04