Dipyridamole

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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C₂₄H₄₀N₈O₄              504.63

Ethanol, 2,2',2",2"'-[(4,8-di-1-piperidinylpyrimido[5,4-d]pyrimidine-2,6-diyl) dinitrilo]tetrakis-;

2,2',2",2"'-[(4,8-Dipiperidinopyrimido [5,4-d]pyrimidine-2,6-diyl) dinitrilo tetraethanol CAS RN^®: 58-32-2; UNII: 64ALC7F90C.

1 DEFINITION

Dipyridamole contains NLT 98.0% and NMT 102.0% of dipyridamole (C₂₄H₄₀N₈O₄), calculated on the dried basis. 

2 IDENTIFICATION

Change to read:

A. ^▲SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K _{▲(CN1-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

3.1 PROCEDURE

Buffer: 0.77 g/L of ammonium acetate. Adjust with glacial acetic acid to a pH of 4.0.

Mobile phase: Methanol and Buffer (700:300)

Standard solution: 0.2 mg/mL of USP Dipyridamole RS in methanol

Sample solution: 0.2 mg/mL of Dipyridamole in methanol

3.1.1 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 288 nm

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

Flow rate: 1.2 mL/min

Injection volume: 10 µL

Run time: NLT 1.7 times the retention time of dipyridamole

3.1.2 System suitability

Sample: Standard solution

3.1.3 Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 0.73%

3.1.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of dipyridamole (C₂₄H₄₀N₈O₄) in the portion of Dipyridamole taken: 

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

r_U = peak response of dipyridamole from the Sample solution

r_S = peak response of dipyridamole from the Standard solution

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

C_U = concentration of Dipyridamole in the Sample solution (mg/mL)

Acceptance criteria: 98.0%-102.0% on the dried basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281): NMT 0.1%

4.2 ORGANIC IMPURITIES

Solution A: 10 mM ammonium formate. Adjust with formic acid to a pH of 5.0.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Standard solution: 0.5 µg/mL each of USP Dipyridamole RS. USP Dipyridamole Related Compound A RS, USP Dipyridamole Related Compound B RS, USP Dipyridamole Related Compound C RS, USP Dipyridamole Related Compound D RS. USP Dipyridamole Related Compound E RS, and USP Dipyridamole Related Compound F RS in methanol

Sample solution: 500 µg/mL of Dipyridamole in methanol

4.2.1 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 295 nm

Column: 2.1-mm × 15-cm; 1.7-µm packing L1

Column temperature: 45°

Flow rate: 0.3 mL/min

Injection volume: 2 µL

4.2.2 System suitability

Sample: Standard solution

4.2.3 Suitability requirements

Resolution: NLT 4.0 between dipyridamole related compound D and dipyridamole

Relative standard deviation: NMT 2.8%

4.2.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each specified impurity in the portion of Dipyridamole taken:

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

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

r_S = peak response of corresponding USP Reference Standard from the Standard solution

C_S = concentration of corresponding USP Reference Standard in the Standard solution (µg/mL)

C_U = concentration of Dipyridamole in the Sample solution (µg/mL)

Calculate the percentage of each unspecified impurity in the portion of Dipyridamole taken:

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

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

r_S = peak response of dipyridamole from the Standard solution S

C_S = concentration of USP Dipyridamole RS in the Standard solution (µg/mL)

C_U = concentration of Dipyridamole in the Sample solution (µg/mL)

Acceptance criteria: See Table 2.

Table 2

5 SPECIFIC TESTS

5.1 CHLORIDE

Sample: 500 mg

Acceptance criteria: No turbidity or precipitate is produced.

5.2 LOSS ON DRYING (731)

Analysis: Dry at 105° for 3 h.

Acceptance criteria: NMT 0.2%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers. Store at room temperature.

USP REFERENCE STANDARDS (11).

USP Dipyridamole RS

USP Dipyridamole Related Compound A RS

2,2'-([4,6,8-Tri(piperidin-1-yl)pyrimido[5,4-d]pyrimidin-2-yl]azanediyl) diethanol.

C₂₅H₄₀N₈O₂              484.64

USP Dipyridamole Related Compound B RS

2,2',2'',2''',2''',2'''''-([8-(Piperidin-1-yl)pyrimido [5,4-d]pyrimidine-2,4,6-triyl]tris(azanetriyl))hexaethanol.

C₂₃H₄₀N₈O₆               524.61

USP Dipyridamole Related Compound C RS

2,2'-([6-Chloro-4,8-di(piperidin-1-yl)pyrimido [5,4-d]pyrimidin-2-yl]azanediyl)diethanol.

C₂₀H₃₀CIN₇O₂           435.95

USP Dipyridamole Related Compound D RS

2,2'-((6-[(2-Hydroxyethyl)amino]-4,8-di(piperidin-1-yl)pyrimido [5,4-d]pyrimidin-2-yl)azanediyl) diethanol.

C₂₂H₃₆N₈O₃          460.57

USP Dipyridamole Related Compound E.RS

2,2',2",2"'-([6,8-Di(piperidin-1-yl)pyrimido [5,4-d]pyrimidine-2,4-diyl]bis(azanetriyl)}tetraethanol.

C₂₂H₄₀N₈O₄         504.63

USP Dipyridamole Related Compound F. RS

2,2',2",2"'-({4-[(2-Hydroxyethyl)amino]-8-(piperidin-1-yl)pyrimido [5,4-d]pyrimidine-2,6-diyl)bis(azanetriyl))tetraethanol.

C₂₁H₃₆N₈O5            480.56