Dapagliflozin Propanediol Monohydrate CAS 960404-48-2 Assay 98.0%~102.0% API High Quality

Dapagliflozin Propanediol
C21H25ClO6 · C3H8O2 · H2O 502.99
D-Glucitol, 1,5-anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-, (1S)-, compd. with (2S)-1,2-propanediol, hydrate (1:1:1);
(1S)-1,5-Anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl) phenyl]-D-glucitol (S)-propane-1,2-diol (1:1) monohydrate;
(2S,3R,4R,5S,6R)-2-[4-Chloro-3-(4-ethoxybenzyl)phenyl]-6- (hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol
(S)-propane-1,2-diol (1:1) monohydrate
CAS RN®: 960404-48-2; UNII: 887K2391VH.
DEFINITION
Dapagliflozin Propanediol contains NLT 98.0% and NMT 102.0% of dapagliflozin (C21H25ClO6) calculated on the anhydrous, propanediol-free, and solvent-free basis.
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.
ASSAY
• PROCEDURE
Solution A: Trifluoroacetic acid and water (0.5: 1000)
Solution B: Trifluoroacetic acid and acetonitrile (0.5: 1000)
Mobile phase: See Table 1.
Table 1
Time (min) Solution A (%) Solution B (%)
0 85 15
2 85 15
36 10 90
39 10 90
40 85 15
45 85 15
Standard solution: 0.2 mg/mL of USP Dapagliflozin
Propanediol RS in acetonitrile
Sample solution: 0.2 mg/mL of Dapagliflozin 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 dapagliflozin (C21H25ClO6) in the portion of Dapagliflozin Propanediol taken:
Result = (rU/rS) × (CS/CU) × 100
rU = peak response of dapagliflozin from the Sample solution
rS = peak response of dapagliflozin from the Standard solution
CS = concentration of USP Dapagliflozin Propanediol RS in the Standard solution (mg/mL)
CU = concentration of Dapagliflozin Propanediol in the Sample solution (mg/mL)
Acceptance criteria: 98.0%-102.0% on the anhydrous, propanediol-free, and solvent-free basis
OTHER COMPONENTS
• 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 Dapagliflozin 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 film 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
Initial Temperature (°) Temperature Ramp (°/min) Final Temperature (°) Hold Time at Final Temperature (min)
150 - 150 2
150 40 240 4
Carrier gas: Helium
Flow rate: 3.5 mL/min
Injection volume: 1.0 µL
Injection type: Split, split flow 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 Dapagliflozin Propanediol taken:
Result = (RU/RS) × (CS/CU) × 100
RU = peak response ratio of propanediol to ethylene glycol from the Sample solution
RS = peak response ratio of propanediol to ethylene glycol from the Standard solution
CS = concentration of USP Propylene Glycol RS in the Standard solution (mg/mL)
CU = concentration of Dapagliflozin Propanediol in the Sample solution (mg/mL)
Acceptance criteria: 14.0%-16.5%
IMPURITIES
• 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 Dapaglifloz in Propanediol RS in acetonitrile
System suitability solution: 0.2 mg/mL of USP Dapagliflozin Propanediol RS and 0.007 mg/mL of USP Dapagliflozin Related Compound A RS in acetonitrile
System suitability
Samples: Standard solution, Sensitivity solution, and System suitability solution
[NOTE-The relative retention times for dapagliflozin and dapagliflozin related compound A are 1.0 and 1.02, respectively.]
Suitability requirements
Resolution: NLT 2.0 between dapagliflozin and dapagliflozin related compound A, System suitability solution
Tailing factor: 0.8-1.5 for dapagliflozin, 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 Dapagliflozin Propanediol taken:
Result = (rU/rT) × 100
rU = peak response of each individual impurity from the Sample solution
rT = sum of all the responses from the Sample solution
Acceptance criteria: See Table 3. The reporting threshold is 0.05%.
Table 3
Name Relative Retention Time Acceptance Criteria, NMT (%)
Dapagliflozin 1.0 -
Ethyldapagliflozina 1.24 0.15
Any individual unspecified impurity - 0.10
Total impurities - 0.30
a (2S,3R,4R,5S,6R)-2-[4-Chloro-3-(4-ethoxy-3-ethylbenzyl)phenyl]-6- (hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol.
SPECIFIC TESTS
• WATER DETERMINATION á921ñ, Method I, Method Ic: 3.2%-4.0%
ADDITIONAL REQUIREMENTS
• PACKAGING AND STORAGE: Preserve in a well-closed container. Store at controlled room temperature.
• USP REFERENCE STANDARDS <11>
USP Dapagliflozin Propanediol RS
USP Dapagliflozin 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)