Ramipril Capsules
DEFINITION
Ramipril Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of C23H32N2O5.
IDENTIFICATION
• A. Ultraviolet Absorption 197U
Phosphoric acid solution:
30 mL/L of phosphoric acid in water
Diluent:
Acetonitrile and Phosphoric acid solution (2:3)
Standard solution:
0.2 mg/mL of USP Ramipril RS in Diluent. Sonicate for 1 min, if necessary, for complete dissolution.
Sample solution:
Use the Sample solution prepared as directed in the Assay.
Wavelength range:
200400 nm
Path length:
0.1-cm cell
• 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
Buffer:
Dissolve 17 g of monobasic potassium phosphate and 11.2 g of sodium perchlorate in 750 mL of water in a 1-L flask. Dilute with water to volume. Adjust with phosphoric acid to a pH of 2.3.
Solution A:
Acetonitrile, Buffer, and water (1:2:2). [NoteDo not filter Solution A. ]
Solution B:
Acetonitrile, Buffer, and water (9:10:6). [NoteDo not filter Solution B. ]
Phosphoric acid solution and Diluent:
Prepare as directed in Identification test A.
Mobile phase:
Use the gradient table below.
Standard solution:
0.2 mg/mL of USP Ramipril RS and 0.002 mg/mL of USP Ramipril Related Compound A RS in Diluent
Sample stock solution:
Transfer the contents of 8 Capsules into each of the flasks as described in Table 1. Add Capsule shells into the flasks. Add acetonitrile per Table 1, and swirl to agitate the contents. Sonicate for 15 min, and mechanically shake for 10 min. Dilute with acetonitrile to volume for Capsule strengths 5.0 and 10 mg only. For 1.25- and 2.5-mg Capsules, use the solution as is without further dilution. [NoteExtracts from the vial cap may result in extraneous peaks. ]
Table 1
Sample solution:
Nominally 0.2 mg/mL of ramipril in Phosphoric acid solution from the Sample stock solution. Pass through a nylon filter of 0.20-µm pore size, and discard the first 2 mL of filtrate.
Chromatographic system
Mode:
LC
Detector:
UV 215 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1 with a guard column, packing L1
Temperature:
60
Flow rate:
1.5 mL/min
Injection size:
50 µL
System suitability
Sample:
Standard solution
Suitability requirements
Resolution:
NLT 2.5 between ramipril and ramipril related compound A
Tailing factor:
NMT 2.5 for the ramipril peak
Relative standard deviation:
NMT 2.0% for the ramipril peak
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C23H32N2O5, based on the label claim, in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria:
90.0%110.0%
PERFORMANCE TESTS
• Dissolution 711
Medium:
0.1 N hydrochloric acid; 500 mL
Apparatus 2:
50 rpm, with sinkers. [NoteA suitable sinker is catalog number CAPWHT-02 available from www.QLA-LLC.com. ]
Time:
30 min
Standard solution:
0.01 mg/mL of USP Ramipril RS in Medium
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Phosphoric acid solution:
Prepare as directed in Identification test A.
Mobile phase:
Acetonitrile and Phosphoric acid solution (2:3)
Chromatographic system
Mode:
LC
Detector:
UV 215 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Temperature:
30
Flow rate:
1 mL/min
Injection size:
25 µL
Suitability requirements
Sample:
Standard solution
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of ramipril dissolved:
Result = (rU/rS) × (CS/L) × V × 100
Tolerances:
NLT 80% (Q) of the labeled amount of ramipril is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
Procedure for content uniformity
Phosphoric acid solution:
Prepare as directed in Identification test A.
Mobile phase:
Acetonitrile and Phosphoric acid solution (2:3). Pass through a nylon filter of 0.45-µm pore size.
Standard solution:
0.03 mg/mL of USP Ramipril RS in Mobile phase. Sonicate for 1 min, if not dissolved completely.
Sample solution:
Transfer the contents of 1 Capsule into a suitable flask as described in Table 2. Add Mobile phase (about 50% of total volume), and sonicate for 25 min. Mechanically shake for 10 min, and dilute with Mobile phase to volume. Further dilute the solution from the 10-mg strength Capsule with Mobile phase, as shown in Table 2. Pass through a nylon filter of 0.20-µm pore size, and discard the first 2 mL of filtrate.
Table 2
Chromatographic system:
Proceed as directed in the test for Dissolution.
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C23H32N2O5, based on the label claim, in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × 100
IMPURITIES
Organic Impurities
• Procedure
Buffer, Solution A, Solution B, Phosphoric acid solution, Diluent, Standard solution, and Sample solution:
Proceed as directed in the Assay.
Sensitivity solution:
0.1 µg/mL of ramipril in Diluent from the Standard solution
Chromatographic system:
Prepare as directed in the Assay.
Suitability requirements
Samples:
Standard solution and Sensitivity solution
Resolution:
NLT 2.5 between ramipril and ramipril related compound A, Standard solution
Tailing factor:
NMT 2.5 for the ramipril peak, Standard solution
Relative standard deviation:
NMT 2.0% for the ramipril peak, Standard solution
Signal-to-noise ratio:
NLT 10 for the ramipril peak, Sensitivity solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100 × (1/F)
Acceptance criteria
Individual impurities:
See Impurity Table.
Total impurities:
NMT 8.0% for Capsule strength 1.25 mg, NMT 7.0% for Capsule strength 2.5 mg, and NMT 6.0% for Capsule strengths 5 mg and 10 mg. [NoteTotal impurities include the sum of individual specified and unspecified degradants. Disregard any peak below 0.1%. ]
Impurity Table
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers, and store at controlled room temperature.
• USP Reference Standards 11
USP Ramipril Related Compound A RS
(2S,3aS,6aS)-1-[(S)2-[[(S)1-(Methoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-octahydrocyclopenta[b]pyrrole-2-carboxylic acid. C22H30N2O5 402.48
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 4519
Pharmacopeial Forum: Volume No. 35(4) Page 867
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