Trandolapril
C24H34N2O5 430.54
1H-Indole-2-carboxylic acid, octahydro N-[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]-1-alanyl (2S,3aR,7aS);
(2S,3aR,7aS)-1-[(S)-N-[(S)-1-Carboxy-3-phenylpropyl]alanyl]hexahydro-2-indolinecarboxylic acid, 1-ethyl ester
[87679-37-6].
Buffer:
6.8 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 3.0.
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C24H34N2O5 430.54
1H-Indole-2-carboxylic acid, octahydro N-[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]-1-alanyl (2S,3aR,7aS);
(2S,3aR,7aS)-1-[(S)-N-[(S)-1-Carboxy-3-phenylpropyl]alanyl]hexahydro-2-indolinecarboxylic acid, 1-ethyl ester
[87679-37-6].DEFINITION
Change to read:
Trandolapril contains NLT 98.0% and NMT 102.0%USP35 of C24H34N2O5, calculated on the anhydrous basis.
NLT 98.0% and NMT 102.0%USP35 of C24H34N2O5, calculated on the anhydrous basis.IDENTIFICATION
• A. Infrared Absorption 
197K
or 197M
197K or 197M
• B.
It complies with the test for Specific Rotation.
ASSAY
Change to read:
• Procedure
Buffer:
6.8 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 3.0.
Mobile phase:
Acetonitrile and Buffer (35:65)
Standard stock solution:
0.1 mg/mL of USP Trandolapril RS in Mobile phase
Standard solution:
0.002 mg/mL in Mobile phase from Standard stock solution
Sample stock solution:
0.08 mg/mL of Trandolapril in Mobile phase
Sample solution:
0.002 mg/mL of Trandolapril in Mobile phase from Sample stock solution
Chromatographic system
Mode:
LC
Detector:
UV 210 nm
Column:
4.6-mm × 15-cm; 3.5-µm packing L1
Column temperature:
40
Flow rate:
1.0 mL/min
Injection size:
100 µL
Run time:
NLT 5.5 times the retention time of trandolapril
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 1.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of trandolapril (C24H34N2O5) in the portion of Trandolapril taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Trandolapril RS in the Standard solution (mg/mL) |
| CU | = | = concentration of Trandolapril in the Sample solution (mg/mL) |
Acceptance criteria:
98.0%–102.0% on the anhydrous basisUSP35
USP35
IMPURITIES
• Procedure 1: Residue on Ignition 281:
NMT 0.1% from 2.0 g
281:
NMT 0.1% from 2.0 g
• Procedure 2
Buffer:
6.8 g/L of monobasic potassium phosphate. Adjust with phosphoric acid to a pH of 2.5 ± 0.1.
Solution A:
Acetonitrile and Buffer (25:75), filtered and degassed
Solution B:
Acetonitrile and Buffer (50:50), filtered and degassed
Mobile phase:
See Table 1.
Table 1
| Time (min) |
Solution A (%) |
Solution B (%) |
|---|---|---|
| 0 | 95 | 5 |
| 20 | 95 | 5 |
| 35 | 5 | 95 |
| 45 | 5 | 95 |
| 46 | 95 | 5 |
| 60 | 95 | 5 |
Standard solution:
0.0025 mg/mL of USP Trandolapril RS in Solution A
System suitability solution:
0.05 mg/mL each of USP Trandolapril Related Compound C RS and USP Trandolapril Related Compound D RS in Solution A
Sample solution:
2.5 mg/mL of Trandolapril in Solution A
Chromatographic system
Mode:
LC
Detector:
UV 210 nm
Column:
4.6-mm × 15-cm; packing L1
Column temperature:
40
Flow rate:
1.3 mL/min
Injection size:
20 µL
System suitability
Samples:
Standard solution and System suitability solution
Suitability requirements
Resolution:
NLT 4 between trandolapril related compound C and trandolapril related compound D, System suitability solution
Tailing factor:
1.5, Standard solution
Relative standard deviation:
NMT 3.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Trandolapril taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
| rU | = | = peak response of each impurity from the Sample solution |
| rS | = | = peak response of trandolapril from the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| CU | = | = concentration of the Sample solution (mg/mL) |
| F | = | = relative response factor (see Table 2) |
Acceptance criteria:
See Table 2. [Note—Do not include trandolapril related compound D in the total impurities. ]
Table 2
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Trandolapril related compound Ca | 2.1 | 0.45 | 0.2 |
| Trandolapril related compound Db | 2.5 | 1.0 | 0.5 |
| Unspecified impurities |
— | 1.0 | 0.1 |
| Total impurities | — | — | 0.5 |
|
a
(2S,3aR,7aS)-1-[N-[(S)-1-Carboxy-3-cyclohexylpropyl]-l-alanyl]hexahydro-2-indolinecarboxylic acid 1-ethyl ester.
b
(S)-Ethyl 2-[(3S,5aS,9aR,10aS)-3-methyl-1,4-dioxodecahydropyrazino[1,2-a]indol-2(1H)-yl)]-4-phenylbutanoate.
|
|||
SPECIFIC TESTS
• Optical Rotation, Specific Rotation 781S
781S
Sample:
0.02 g/mL in dehydrated alcohol
Acceptance criteria:
16.5 to 18.5 at 20
16.5 to 18.5 at 20
• Water Determination, Method Ic 921:
NMT 0.2% from 2 g
921:
NMT 0.2% from 2 g
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight, light-resistant containers. Store at room temperature.
• USP Reference Standards 11
11
USP Trandolapril RS 
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USP Trandolapril Related Compound C RS
(2S,3aR,7aS)-1-[N-[(S)-1-Carboxy-3-cyclohexylpropyl]-l-alanyl]hexahydro-2-indolinecarboxylic acid 1-ethyl ester.
C24H40N2O5 436.58
(2S,3aR,7aS)-1-[N-[(S)-1-Carboxy-3-cyclohexylpropyl]-l-alanyl]hexahydro-2-indolinecarboxylic acid 1-ethyl ester.
C24H40N2O5 436.58
USP Trandolapril Related Compound D RS
(S)-Ethyl 2-[(3S,5aS,9aR,10aS)-3-methyl-1,4-dioxodecahydropyrazino[1,2-a]indol-2(1H)-yl)]-4-phenylbutanoate.
C24H32N2O4 412.52
(S)-Ethyl 2-[(3S,5aS,9aR,10aS)-3-methyl-1,4-dioxodecahydropyrazino[1,2-a]indol-2(1H)-yl)]-4-phenylbutanoate.
C24H32N2O4 412.52
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Sujatha Ramakrishna, Ph.D.
Senior Scientific Liaison 1-301-816-8349 |
(SM22010) Monographs - Small Molecules 2 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 4908
Pharmacopeial Forum: Volume No. 37(1)