Telmisartan
C33H30N4O2 514.62
[1,1¢-Biphenyl]-2-carboxylic acid, 4¢-[(1,4¢-dimethyl-2¢-propyl[2,6¢-bi-1H-benzimidazol]-1¢-yl)methyl-];
4¢-[[4-Methyl-6-(1-methyl-2-benzimidazolyl)-2-propyl-1-benzimidazolyl]methyl]-2-biphenylcarboxylic acid
[144701-48-4].
(tel'' mi sar' tan).
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C33H30N4O2 514.62
[1,1¢-Biphenyl]-2-carboxylic acid, 4¢-[(1,4¢-dimethyl-2¢-propyl[2,6¢-bi-1H-benzimidazol]-1¢-yl)methyl-];
4¢-[[4-Methyl-6-(1-methyl-2-benzimidazolyl)-2-propyl-1-benzimidazolyl]methyl]-2-biphenylcarboxylic acid
[144701-48-4].DEFINITION
Telmisartan contains NLT 98.0% and NMT 101.0% of C33H30N4O2, calculated on the dried basis.
IDENTIFICATION
• A. Infrared Absorption 
197K
:
If the spectra obtained shows differences, proceed with the samples prepared as follows. Separately dissolve a quantity of USP Telmisartan RS and the Telmisartan sample in alcohol. [Note—Heating the solution may be necessary for complete dissolution. ] Cool the solution in an ice bath, filter the crystals, and dry at 105
.
197K:
If the spectra obtained shows differences, proceed with the samples prepared as follows. Separately dissolve a quantity of USP Telmisartan RS and the Telmisartan sample in alcohol. [Note—Heating the solution may be necessary for complete dissolution. ] Cool the solution in an ice bath, filter the crystals, and dry at 105.
• B.
The retention time of the major peak from the Sample solution corresponds to that from the Standard solution, as obtained in the test for Organic Impurities.
ASSAY
• Procedure
(See Titrimetry 541.)
541.)
Sample solution:
190 mg of Telmisartan in 5 mL of anhydrous formic acid. Dilute with 75 mL of acetic anhydride.
Analysis:
Titrate with 0.1 M perchloric acid versus a blank determination under the same conditions. Each mL of 0.1 M perchloric acid is equivalent to 25.73 mg of C33H30N4O2.
Acceptance criteria:
98.0%–101.0% on the dried basis
IMPURITIES
• Residue on Ignition 281:
NMT 0.1%. A 1-g sample is used.
281:
NMT 0.1%. A 1-g sample is used.
• Organic Impurities
[Note—Freshly prepare sample solutions, and protect from light. ]
Solution A:
2.0 g of monobasic potassium phosphate and 3.8 g of sodium 1-pentanesulfonate in 1 L of water. Adjust with 1 M phosphoric acid to a pH of 3.0.
Solution B:
Acetonitrile and methanol (4:1)
Mobile phase:
See Table 1.
Table 1
| Time (min) |
Solution A (%) |
Solution B (%) |
|---|---|---|
| 0 | 70 | 30 |
| 2 | 70 | 30 |
| 27 | 20 | 80 |
| 32 | 20 | 80 |
| 32.1 | 70 | 30 |
| 37 | 70 | 30 |
System suitability solution:
Dissolve USP Telmisartan RS and USP Telmisartan Related Compound B RS in methanol (0.2 mL/mg of USP Telmisartan RS) and 100 µL of 1 M sodium hydroxide solution. Sonicate to dissolve. The final concentration is 2.5 mg/mL of the USP Telmisartan RS and 2.5 µg/mL of USP Telmisartan Related Compound B RS in methanol.
Standard solution:
Dissolve USP Telmisartan RS in methanol (0.2 mL/mg of USP Telmisartan RS) and 100 µL of 1 M sodium hydroxide solution. Sonicate to dissolve. The final concentration is 0.025 mg/mL.
Sample solution:
Dissolve Telmisartan in methanol (0.2 mL/mg of Telmisartan) and 100 µL of 1 M sodium hydroxide solution. Sonicate to dissolve. The final concentration is 2.5 mg/mL.
Chromatographic system
Mode:
LC
Detector:
UV 230 nm
Column:
4.0-mm × 12.5-cm; 5-µm packing L1
Column temperature:
40
Flow rate:
1 mL/min
Injection size:
2 µL
System suitability
Samples:
System suitability solution and Standard solution
Suitability requirements
Resolution:
NLT 3.0 between telmisartan and telmisartan related compound B, System suitability solution
Tailing factor:
Between 0.9 and 1.5 for telmisartan related compound B, System suitability solution
Relative standard deviation:
NMT 5.0% for the telmisartan peak, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of any individual impurity in the portion of Telmisartan taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of each impurity from the Sample solution |
| rS | = | = peak response of telmisartan from the Standard solution |
| CS | = | = concentration of USP Telmisartan RS in the Standard solution |
| CU | = | = concentration of Telmisartan in the Sample solution |
Acceptance criteria:
See Table 2. [Note—Calculate the total impurities from the sum of all impurity peaks greater than or equal to 0.05%. ]
Table 2
| Name | Relative Retention Time |
Acceptance Criteria, NMT (%) |
|---|---|---|
| Telmisartan related compound Aa | 0.3 | 0.1 |
| Telmisartan amideb | 0.7 | 0.1 |
| Telmisartan related compound Bc | 0.9 | 0.1 |
| Telmisartan diacidd | 0.67 | 0.1 |
| Telmisartan tert-butyl estere | 1.7 | 0.2 |
| Telmisartan unknown impurity | 1.8 | 0.2 |
| Any other individual impurity | — | 0.1 |
| Total impurities | — | 1.0 |
|
a
1,7¢-Dimethyl-2¢-propyl-1H,3¢H-2,5¢-bibenzo[d]imidazole.
b
4¢-[(1,7¢-Dimethyl-2¢-propyl-1H,3¢H-2,5¢-bibenzo[d]imidazol-3¢-yl)methyl]biphenyl-2-carboxamide.
c
4¢-[(1,7¢-Dimethyl-2¢-propyl-1H,1¢H-2,5¢-bibenzo[d]imidazol-1¢-yl)methyl]biphenyl-2-carboxylic acid.
d
1-[(2¢-Carboxybiphenyl-4-yl)methyl]-4-methyl-2-propyl-1H-benzimidazole-6-carboxylic acid.
e
tert-Butyl 4¢-[(1,7¢-dimethyl-2¢-propyl-1H,3¢H-2,5¢-bibenzo[d]imidazol-3¢-yl)methyl]biphenyl-2-carboxylate.
|
||
SPECIFIC TESTS
• Loss on Drying 731:
Dry 1.0 g of the sample at 105 to constant weight: it loses NMT 1.5%.
731:
Dry 1.0 g of the sample at 105 to constant weight: it loses NMT 1.5%.
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers, and protect from light.
• USP Reference Standards 11
11
USP Telmisartan RS 
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USP Telmisartan Related Compound B RS
4¢-[(1,7¢-Dimethyl-2¢-propyl-1H,1¢H-2,5¢-bibenzo[d]imidazol-1¢-yl)methyl]biphenyl-2-carboxylic acid.
C33H30N4O2 514.62
4¢-[(1,7¢-Dimethyl-2¢-propyl-1H,1¢H-2,5¢-bibenzo[d]imidazol-1¢-yl)methyl]biphenyl-2-carboxylic acid.
C33H30N4O2 514.62
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 4776
Pharmacopeial Forum: Volume No. 37(1)