Dexamethasone Sodium Phosphate

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 

Dexamethasone Sodium Phosphate contains NLT 97.0% and NMT 102.0% of dexamethasone sodium phosphate (C₂₂H₂₈FNa₂O₈P), calculated on the anhydrous and solvent-free basis. 

2 IDENTIFICATION 

Change to read: 

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020) : If the spectra obtained in the solid state show differences, dissolve the substance to be examined and the Reference Standard separately in a minimum of alcohol, evaporate on a water bath to dryness, and repeat the test on the residues. 

B. Identification Tests—General, Phosphate〈191〉: The residue from its ignition meets the requirements. 

C. Identification Tests—General, Sodium〈191〉: The residue from its ignition meets the requirements. 

3 ASSAY 

3.1 Procedure 

Mobile phase: Mix 520 mL of water with 2 mL of phosphoric acid. Bring the temperature to 20°, and adjust with sodium hydroxide to a pH of 2.6. Mix this solution with 36 mL of tetrahydrofuran and 364 mL of methanol. 

System suitability stock solution: 0.02 mg/mL each of USP Dexamethasone Sodium Phosphate RS and USP Dexamethasone RS, prepared as follows. Dissolve 2 mg of each compound in 2 mL of tetrahydrofuran, and dilute with Mobile phase to 100 mL. 

System suitability solution: 2 µg/mL each of USP Dexamethasone Sodium Phosphate RS and USP Dexamethasone RS in Mobile phase from the System suitability stock solution 

Standard solution: 0.06 mg/mL of USP Dexamethasone Sodium Phosphate RS in Mobile phase 

Sample solution: 0.06 mg/mL of Dexamethasone Sodium Phosphate in Mobile phase 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 4.6-mm × 15-cm; 7-µm packing L1 

Flow rate: 1.5 mL/min 

Injection volume: 20 µL 

Run time: 3 times the retention time of the dexamethasone sodium phosphate peak 

System suitability 

[Note—The relative retention times of the dexamethasone sodium phosphate and dexamethasone peaks are 1.0 and 2.0, respectively.] Samples: System suitability solution and Standard solution 

Suitability requirements 

Resolution: NLT 6.0 between dexamethasone sodium phosphate and dexamethasone peaks, System suitability solution Relative standard deviation: NMT 2.0%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of dexamethasone sodium phosphate (C₂₂H₂₈FNa₂O₈P) in the portion of Dexamethasone Sodium Phosphate taken: 

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response from the Sample solution 

r_s = peak response from the Standard solution 

C_s = concentration of USP Dexamethasone Sodium Phosphate RS in the Standard solution (mg/mL) 

C_u = nominal concentration of Dexamethasone Sodium Phosphate in the Sample solution (mg/mL) 

Acceptance criteria: 97.0%–102.0% on the anhydrous and solvent-free basis 

4 IMPURITIES 

4.1 Limit of Phosphate Ions 

Solution A: 50 mg/mL of ammonium molybdate in 1 N sulfuric acid 

Solution B: Dissolve 350 mg of p-methylaminophenol sulfate in 50 mL of water, add 20 g of sodium bisulte, mix to dissolve, and dilute with water to 100 mL. 

Standard stock solution: 0.14 mg/mL of dried monobasic potassium phosphate in water. This solution contains the equivalent of 0.10 mg/mL of phosphate (PO₄) ion. 

Standard solution: In a 25-mL volumetric ask, mix 5.0 mL of Standard stock solution, 10 mL of water, and 5 mL of 2 N sulfuric acid. Add 1 mL each of Solution A and Solution B, dilute with water to volume, and allow to stand at room temperature for 30 min. Prepare concomitantly with the Sample solution. 

Sample solution: In a 25-mL volumetric ask, dissolve 50 mg of Dexamethasone Sodium Phosphate in a mixture of 10 mL of water and 5 mL of 2 N sulfuric acid, by warming if necessary. Add 1 mL each of Solution A and Solution B, dilute with water to volume, and allow to stand at room temperature for 30 min. 

Instrumental conditions 

(See Ultraviolet-Visible Spectroscopy 〈857〉.) 

Mode: Visible 

Analytical wavelength: 730 nm 

Cell: 1 cm 

Blank: Water 

Analysis 

Samples: Standard solution and Sample solution 

Acceptance criteria: The absorbance of the Sample solution is NMT that of the Standard solution. The limit is 1.0% of phosphate (PO₄).

4.2 Limit of Alcohol 

Internal standard solution: 0.4 mg/mL of acetonitrile, prepared as follows. Dilute 5.0 mL of USP Alcohol Determination–Acetonitrile RS with water to 200.0 mL. 

Standard stock solution: 0.20 mg/mL of alcohol, prepared as follows. Dilute 25.0 mL of USP Alcohol Determination–Alcohol RS with water to 2000.0 mL. 

Standard solution: 0.08 mg/mL of alcohol, prepared as follows. Dilute 10.0 mL of the Standard stock solution and 5.0 mL of the Internal standard solution with water to 25.0 mL. 

Sample solution: 5.0 mg/mL of Dexamethasone Sodium Phosphate, prepared as follows. Transfer 125 mg of Dexamethasone Sodium Phosphate to a 25-mL volumetric ask, add 5.0 mL of the Internal standard solution, and dilute with water to volume. Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: GC 

Detector: Flame ionization 

Column: 0.53-mm × 30-m capillary coated with 3-µm lm of G43 

Carrier gas: Hydrogen 

Linear velocity: 36 cm/s 

Split ratio: 2:1 

Temperatures 

Injection port: 210° 

Detector: 280° 

Column: See Table 1. 

Table 1 

Injection volume: 0.4 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Resolution: NLT 2.0 between alcohol and acetonitrile 

Relative standard deviation: NMT 3.0% for alcohol 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of alcohol in the portion of Dexamethasone Sodium Phosphate taken: 

Result = (R_u/R_s) × (C_s/C_u) × 100

R_u = peak response ratio of the alcohol to the internal standard from the Sample solution 

R_s = peak response ratio of the alcohol to the internal standard from the Standard solution 

C_s = concentration of alcohol in the Standard solution (mg/mL) 

C_u = concentration of Dexamethasone Sodium Phosphate in the Sample solution (mg/mL) 

Acceptance criteria: NMT 1.5% 

4.3 Organic Impurities 

Buffer: 7.0 g/L of ammonium acetate in water 

Solution A: Mix 300 mL of Buffer and 350 mL of water, adjust with 5 M acetic acid to a pH of 3.8, and then add 350 mL of methanol. Solution B: Adjust 300 mL of Buffer with 5 M acetic acid to a pH of 4.0, and then add 700 mL of methanol. 

Mobile phase: See Table 2. 

Table 2 

System suitability solution: 0.02 mg/mL each of USP Dexamethasone Sodium Phosphate RS and USP Betamethasone Sodium Phosphate RS in Solution A 

Standard solution: 1 µg/mL of USP Dexamethasone Sodium Phosphate RS in Solution A 

Sample solution: 1 mg/mL of Dexamethasone Sodium Phosphate in Solution A 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 4.6-mm × 12.5-cm; 5-µm packing L7 

Column temperature: 30° 

Flow rate: 1 mL/min 

Injection volume: 20 µL 

System suitability 

Samples: System suitability solution and Standard solution 

Suitability requirements 

Resolution: NLT 2.0 between dexamethasone sodium phosphate and betamethasone sodium phosphate peaks, System suitability solution Relative standard deviation: NMT 5.0%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of each impurity in the portion of Dexamethasone Sodium Phosphate taken: 

Result = (r_u/r_s) × (C_s/C_u) × (1/F) × 100 

r_u = peak response of each impurity from the Sample solution 

r_s = peak response of dexamethasone phosphate from the Standard solution 

C_s = concentration of USP Dexamethasone Sodium Phosphate RS in the Standard solution (µg/mL) 

C_u = concentration of Dexamethasone Sodium Phosphate in the Sample solution (µg/mL) 

F = relative response factor (see Table 3) 

Acceptance criteria: See Table 3. Disregard any peak below 0.05%. 

Table 3 

a 9-Fluoro-11β,17,21-trihydroxy-16α-methyl-16(17)a-homopregna-1,4-diene-3,16a,20-trione 21-(dihydrogen phosphate) disodium salt. 

b 9-Fluoro-11β,17,21-trihydroxy-16β-methyl-16(17)a-homopregna-1,4-diene-3,16a,20-trione 21-(dihydrogen phosphate) disodium salt.

c 9-Fluoro-11β,17a,21-trihydroxy-16β-methyl-16(17)a-homopregna-1,4-diene-3,16a,20-trione 21-(dihydrogen phosphate) disodium salt.

d 9-Fluoro-11β,17,21-trihydroxy-16α-methyl-13(17)a-homopregna-1,4-diene-3,13a,20-trione 21-(dihydrogen phosphate) disodium salt.

e Ethyl 11β,17α-dihydroxy-9-uoro-16α-methylandrostane-1,4-diene-3-one-17-ylcarboxylate. 

f 9-Fluoro-11β,17α-dihydroxy-16α-methylandrosta-1,4-diene-3-one-17β-carboxylic acid. 

g Sodium bis[9-uoro-11β,17-dihydroxy-16α-methylpregna-1,4-diene-3,20-dione 21-yl]phosphate. 

5 SPECIFIC TESTS 

5.1 Optical Rotation, Specific Rotation〈781S〉 

Sample solution: 10 mg/mL in water 

Acceptance criteria: +74° to +82°, calculated on the anhydrous and solvent-free basis 

5.2 pH 〈791〉 

Sample solution: 10 mg/mL 

Acceptance criteria: 7.5–10.5 

5.3 Water Determination, Method I〈921〉 

Acceptance criteria: NMT 10.0% 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in tight containers. 

USP Reference Standards 〈11〉 

USP Alcohol Determination–Acetonitrile RS 

USP Alcohol Determination–Alcohol RS 

USP Betamethasone Sodium Phosphate RS 

USP Dexamethasone RS 

USP Dexamethasone Sodium Phosphate RS