Timolol Maleate Tablets

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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1 DEFINITION

Timolol Maleate Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of timolol maleate (C₁₃H₂₄N₄O₃S · C₄H₄O₄).

2 IDENTIFICATION

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. The UV (or UV-Vis) spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

PROCEDURE

Solution A: Transfer 0.5 mL of trifluoroacetic acid to a 1-L volumetric flask and dilute with water to volume.

Solution B: Transfer 0.5 mL of trifluoroacetic acid to a 1-L volumetric flask and dilute with acetonitrile to volume.

Mobile phase: See Table 1

Table 1

Buffer: Transfer 11.04 g of monobasic sodium phosphate to a 1-L volumetric flask and dilute with water to volume. Adjust with phosphoric acid to a pH of 2.8 ± 0.05.

Diluent: Methanol and Buffer (20:80)

System suitability solution: 0.1 mg/mL of USP Timolol Maleate RS and 10.0 µg/mL of USP Timolol Related Compound D RS in Diluent with sonication if necessary 

Standard solution: 0.1 mg/mL of USP Timolol Maleate RS in Diluent with sonication if necessary

Sample solution: 0.1 mg/mL of timolol maleate from NLT 20 finely ground Tablets (ground with a mortar and pestle) in Diluent with sonication if necessary, and filtration with 0.2-um syringe filters, discarding the first 2 mL

Chromatographic system

(See Chromatography (621). System Suitability.)

Mode: LC

Detector: UV 295 nm. For Identification test B, use a diode array detector in the range of 210-400 nm.

Column: 2.1-mm x 10-cm; 2.6-µm packing L1

Flow rate: 0.4 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times are listed in Table 2.1

Suitability requirements

Resolution: NLT 2.5 between timolol and timolol related compound D, System suitability solution

Tailing factor: NMT 2.5, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of timolol maleate (C₁₃H₂₄N₄O₃S · C₄H₄O₄) in the portion of Tablets taken:

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

C_U = nominal concentration of timolol maleate in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

Medium: 0.1 N hydrochloric acid; 500 mL

Apparatus 1: 100 rpm

Time: 20 min

Standard solution: USP Timolol Maleate RS in Medium

Sample solution: Sample per the chapter. Dilute with Medium to a concentration that is similar to that of the Standard solution.

Analysis: Determine the amount of timolol maleate in solution in filtered portions of the Sample solution, in comparison with the Standard solution, using the procedure in the Assay.

Tolerances: NLT 80% (Q) of the labeled amount of timolol maleate (C₁₃H₂₄N₄O₃S · C₄H₄O₄) is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

ORGANIC IMPURITIES

Mobile phase, Buffer, Diluent, and Chromatographic system: Proceed as directed in the Assay.

System suitability solution: 0.1 mg/mL of USP Timolol Maleate RS and 10 µg/mL of USP Timolol Related Compound D RS in Diluent with sonication if necessary

Standard solution: 2.0 µg/ml each of USP Timolol Maleate RS, USP Timolol Related Compound B RS, and USP Timolol Related Compound D RS in Diluent

Sample solution: 1.0 mg/mL of timolol maleate from NLT 20 finely ground Tablets (ground with a mortar and pestle) in Diluent with sonication if necessary, and filtration with 0.2-um syringe filters, discarding the first 2 mL

System suitability

Samples: System suitability solution and Standard solution [NOTE-The relative retention times are listed in Table 2.]

Suitability requirements

Resolution: NLT 3 between timolol and timolol related compound D, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of timolol maleate related compound B and timolol maleate related compound D the portion of Tablets taken:

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

r_U = peak response of each impurity from the Sample solution 

r_S = peak response of each impurity from the Standard solution

C_S = concentration of each impurity in the Standard solution (mg/mL)

C_U = nominal concentration of timolol maleate in the Sample solution (mg/mL)

Calculate the percentage of any individual unspecified impurity in the portion of Tablets taken:

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

r_U = peak response of any impurity from the Sample solution

r_S = peak response of timolol from the Standard solution

C_S = concentration of USP Timolol Maleate RS in the Standard solution

C_U = nominal concentration of timolol maleate in the Sample solution

Acceptance criteria: See Table 2. Disregard any impurity peaks less than 0.05%.

Table 2

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers.

USP REFERENCE STANDARDS (11)

USP Timolol Maleate RS

USP Timolol Related Compound B RS

3-(tert-Butylamino)-2-(4-morpholino-1,2,5-thiadiazol-3-yloxy)propan-1-ol.

C₁₃H₂₄N₄O₃S         316.42

USP Timolol Related Compound D RS

4-Morpholino-1,2,5-thiadiazol-3-ol.

C₆H₉N₃O₂S         187.22