Dapagliozin Propanediol

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 

Dapagliozin Propanediol contains NLT 98.0% and NMT 102.0% of dapagliozin (C₂₁H₂₅ClO₆) calculated on the anhydrous, propanediol-free, and solvent-free basis. 

2 IDENTIFICATION 

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197A or 197K 

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 

3.1 Procedure 

Solution A: Triuoroacetic acid and water (0.5: 1000) 

Solution B: Triuoroacetic acid and acetonitrile (0.5: 1000) 

Mobile phase: See Table 1. 

Table 1 

Standard solution: 0.2 mg/mL of USP Dapagliozin Propanediol RS in acetonitrile 

Sample solution: 0.2 mg/mL of Dapagliozin Propanediol in acetonitrile 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 220 nm 

Column: 4.6-mm × 15-cm; 3.5-µm packing L1 

Column temperature: 30° 

Flow rate: 1 mL/min 

Injection volume: 10 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Tailing factor: 0.8–1.5 

Relative standard deviation: NMT 0.85% for 6 injections 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of dapagliozin (C₂₁H₂₅ClO₆) in the portion of Dapagliozin Propanediol taken: 

Result = (r_u/r_s) × (C_s/C_u) × 100 

r_u = peak response of dapagliozin from the Sample solution 

r_s = peak response of dapagliozin from the Standard solution 

C_s = concentration of USP Dapagliozin Propanediol RS in the Standard solution (mg/mL) 

C_u = concentration of Dapagliozin Propanediol in the Sample solution (mg/mL) 

Acceptance criteria: 98.0%–102.0% on the anhydrous, propanediol-free, and solvent-free basis 

4 OTHER COMPONENTS 

4.1 Content of Propanediol 

Internal standard solution: 2.64 mg/mL of USP Ethylene Glycol RS in dimethylacetamide 

Standard solution: 3.0 mg/mL of USP Propylene Glycol RS in Internal standard solution 

Sample solution: 20 mg/mL of Dapagliozin Propanediol in Internal standard solution 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: GC 

Detector: Flame ionization 

Column: 0.32-mm × 15-m fused silica; coated with a 0.5-µm lm of phase G14. [Note—Phases of G15, G16, G20, or G39 may also be suitable for use.] 

Temperatures 

Injection port: 240° 

Detector: 240° 

Column: See Table 2. 

Table 2 

Carrier gas: Helium 

Flow rate: 3.5 mL/min 

Injection volume: 1.0 µL 

Injection type: Split, split ow 80.8 mL/min 

Run time: NLT 5 times the retention time of propanediol 

System suitability 

Sample: Standard solution 

[Note—The relative retention times for propanediol and ethylene glycol are 1.0 and 1.1, respectively.] 

Suitability requirements 

Resolution: NLT 1.5 between propanediol and ethylene glycol 

Relative standard deviation: NMT 3.0% for propanediol and ethylene glycol 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of propanediol in the portion of Dapagliozin Propanediol taken: 

Result = (R_u/R_s) × (C_s/C_u) × 100 

R_u = peak response ratio of propanediol to ethylene glycol from the Sample solution 

R_s = peak response ratio of propanediol to ethylene glycol from the Standard solution  

C_s = concentration of USP Propylene Glycol RS in the Standard solution (mg/mL)  

C_u = concentration of Dapagliozin Propanediol in the Sample solution (mg/mL) 

Acceptance criteria: 14.0%–16.5% 

5 IMPURITIES 

5.1 Organic Impurities 

Solution A, Solution B, Mobile phase, Standard solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay. Sensitivity solution: 0.1 µg/mL of USP Dapagliozin Propanediol RS in acetonitrile 

System suitability solution: 0.2 mg/mL of USP Dapagliozin Propanediol RS and 0.007 mg/mL of USP Dapagliozin Related Compound A RS in acetonitrile 

System suitability 

Samples: Standard solution, Sensitivity solution, and System suitability solution 

[Note—The relative retention times for dapagliozin and dapagliozin related compound A are 1.0 and 1.02, respectively.] Suitability requirements 

Resolution: NLT 2.0 between dapagliozin and dapagliozin related compound A, System suitability solution 

Tailing factor: 0.8–1.5 for dapagliozin, Standard solution 

Signal-to-noise ratio: NLT 10, Sensitivity solution 

Analysis 

Sample: Sample solution 

Calculate the percentage of each individual impurity in the portion of Dapagliozin Propanediol taken: 

Result = (r_U/r_T)  × 100 

r_U = peak response of each individual impurity from the Sample solution 

r_T = sum of all the responses from the Sample solution 

Acceptance criteria: See Table 3. The reporting threshold is 0.05%. 

Table 3 

a (2S,3R,4R,5S,6R)-2-[4-Chloro-3-(4-ethoxy-3-ethylbenzyl)phenyl]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol. 

6 SPECIFIC TESTS 

Water Determination 〈921〉, Method I, Method Ic: 3.2%–4.0% 

7 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in a well-closed container. Store at controlled room temperature. 

USP Reference Standards 〈11〉 

USP Dapagliozin Propanediol RS 

USP Dapagliozin Related Compound A RS 

(2S,3R,4R,5S,6R)-2-[4-Bromo-3-(4-ethoxybenzyl)phenyl]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol. 

C₂₁H₂₅BrO₆               453.33    

USP Ethylene Glycol RS 

Ethane-1,2-diol. 

C₂H₆O₂        62.07  

USP Propylene Glycol RS 

Propane-1,2-diol. 

C₃H₈O₂              76.10 (USP 1-Dec-2023)