Trandolapril Tablets
DEFINITION
Trandolapril Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of trandolapril (C24H34N2O5).
IDENTIFICATION
• 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:
8.9 g/L of anhydrous disodium hydrogen phosphate. Add 1 mL of triethylamine and adjust with phosphoric acid to a pH of 3.5. Pass through a suitable filter of 0.45-µm pore size.
Mobile phase:
Acetonitrile and Buffer (2:3)
Diluent:
Acetonitrile and water (2:3)
Standard solution:
40 µg/mL of USP Trandolapril RS in Diluent. [Note—Initially add Diluent (up to 70% of the volume of the flask) to facilitate dissolution before diluting to volume, using sonication if necessary. ]
Sample solution:
40 µg/mL of trandolapril from NLT 10 Tablets in Diluent. [Note—Initially add Diluent (up to 70% of the volume of the flask) to facilitate dissolution before diluting to volume, using sonication (up to 30 min) if necessary, with occasional swirling. ] Pass a portion of the solution through a membrane filter of 0.45-µm pore size.
Chromatographic system
Mode:
LC
Detector:
216 nm
Column:
4.6-mm × 15-cm; 3-µm packing L1
Flow rate:
1.2 mL/min
Injection volume:
20 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Column efficiency:
NLT 3000 theoretical plates
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of trandolapril in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of trandolapril from the Sample solution |
| rS | = | = peak response of trandolapril from the Standard solution |
| CS | = | = concentration of USP Trandolapril RS in the Standard solution (µg/mL) |
| CU | = | = concentration of trandolapril in the Sample solution (µg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 
711
711
Medium:
Water; 500 mL, deaerated
Apparatus 2:
50 rpm
Time:
45 min
Mobile phase and System suitability:
Proceed as directed in the Assay.
Chromatographic system:
Proceed as directed in the Assay, except for the Injection volume.
Injection volume:
100 µL
Stock standard solution:
Prepare 0.2 mg/mL of USP Trandolapril RS as follows. To USP Trandolapril RS in a suitable volumetric flask add acetonitrile to about 5% of the volume of the flask, sonicate to dissolve, and then dilute with Medium.
Standard solution:
Further dilute the solution with Medium to obtain a final concentration of (L/500) mg/mL, where L is the Tablet label claim in mg.
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Calculate the percentage of the labeled amount of trandolapril dissolved:
Result = (rU/rS) × (CS/L) × V × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| L | = | = label claim (mg/Tablet) |
| V | = | = volume of Medium, 500 mL |
Tolerances:
NLT 80% (Q) of the labeled amount of trandolapril (C24H34N2O5) is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Buffer:
7.0 g/L of sodium perchlorate in water (0.05 M). Add 2 g of octanesulfonic acid sodium salt followed by 1 mL of triethylamine. Adjust with diluted perchloric acid (1 in 10) to a pH of 2.0. Pass through a membrane filter of 0.45-µm pore size.
Solution A:
Acetonitrile, tetrahydrofuran, and Buffer (11:1:28)
Solution B:
Acetonitrile and Buffer (3:1)
Mobile phase:
See the gradient table below.
| Time (min) |
Solution A (%) |
Solution B (%) |
|---|---|---|
| 0 | 85 | 15 |
| 25 | 85 | 15 |
| 50 | 50 | 50 |
| 55 | 85 | 15 |
| 65 | 85 | 15 |
Diluent:
Acetonitrile and Buffer (2:3)
Standard stock solution 1:
0.06 mg/mL of each of USP Trandolapril Related Compound C RS and USP Trandolapril Related Compound D RS in acetonitrile. Sonicate to dissolve.
System suitability solution:
0.6 mg/mL of USP Trandolapril RS and 6 µg/mL each of USP Trandolapril Related Compound C RS and USP Trandolapril Related Compound D RS (from Standard stock solution 1) in Diluent. [Note—Initially add Diluent up to 70% of the volumetric flask, sonicate to dissolve, and cool to room temperature. ]
Standard stock solution 2:
0.3 mg/mL of USP Trandolapril RS in Diluent. [Note—Initially add Diluent up to 70% of the volumetric flask, sonicate, and cool to room temperature. ]
Standard solution:
6 µg/mL of USP Trandolapril RS in Diluent from Standard stock solution 2
Sample solution:
0.6 mg/mL of trandolapril in Diluent from NLT 15 Tablets. [Note—Initially add Diluent up to 50% of the volume of the flask and sonicate for 30 min to dissolve. ]
Chromatographic system
Mode:
LC
Detector:
210 nm
Column:
4.6-mm × 25-cm; 5-µm packing L1
Column temperature:
40
Flow rate:
1.5 mL/min
Injection volume:
50 µL
System suitability
Samples:
System suitability solution and Standard solution
Suitability requirements
Resolution:
NLT 3.0 between trandolapril related compound C and trandolapril related compound D, System suitability solution
Column efficiency:
NLT 7000 theoretical plates, Standard solution
Relative standard deviation:
NMT 5.0%, Standard 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) × (1/F) × 100
| rU | = | = peak response of trandolapril in the Sample solution |
| rS | = | = peak response of USP Trandolapril RS in the Standard solution |
| CS | = | = concentration of the Standard solution (µg/mL) |
| CU | = | = concentration of the Sample solution (µg/mL) |
| F | = | = relative response factor (see Impurity Table 1) |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Trandolaprilatea | 0.41 | 1.00 | 2.0 |
| Trandolapril | 1.00 | 1.00 | — |
| Trandolapril related compound C | 1.84 | — | * |
| Trandolapril related compound D | 1.96 | 0.78 | 5.0 |
| Any other individual impurity | — | 1.00 | 1.0 |
| Total impurities | — | — | 7.0 |
|
a
(2S,3aR,7aS)-1-[(2S)-2-[[(1S)-1-Carboxy-3-phenylpropyl]amino]propanoyl]octahydro-1H-indole-2-carboxylic acid.
*
Process-related impurity.
|
|||
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers. Store at controlled room temperature.
• USP Reference Standards 11
11
USP Trandolapril RS 
') + '&img=../../images/v35300/cas-87679-37-6.gif',600,500);)
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 hydrochloride.
C24H40N2O5·HCl 473.05
(2S,3aR,7aS)-1-[N-[(S)-1-Carboxy-3-cyclohexylpropyl]-l-alanyl]hexahydro-2-indolinecarboxylic acid 1-ethyl ester hydrochloride.
C24H40N2O5·HCl 473.05
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 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 4909
Pharmacopeial Forum: Volume No. 36(4) Page 932