Travoprost Ophthalmic Solution

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

Travoprost Ophthalmic Solution is a sterile buffered aqueous solution of Travoprost. It contains NLT 90.0% and NMT 110.0% of the labeled amount of travoprost (C₂₆H₃₅F₃O₆). It may contain suitable stabilizers, buffers, and antimicrobial agents.

[CAUTION-Great care should be taken when handling the active ingredient to avoid contact with the body.]

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 spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Change to read:

PROCEDURE

Buffer: 2.18 mg/mL of sodium 1-octanesulfonate in water. Adjust with phosphoric acid to a pH of 3.5.

Mobile phase: Acetonitrile and Buffer (17:33)

Standard solution: 0.04 mg/mL of travoprost from USP Travoprost RS in a mixture of acetonitrile and water (3:7)

Sample solution: Use Ophthalmic Solution without dilution.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 220 nm. For Identification B, use a diode array detector in the range of 190-400 nm.

Column: 4.6-mm x 15-cm; 5-um packing L1

Flow rate: 2.0 mL/min

Injection volume: 100 µL

System suitability

Sample: Standard solution

[NOTE-USP Travoprost RS contains a small percentage of the 5,6-trans isomer. The relative retention times for travoprost and the 5,6-trans isomer are 1.0 and 1.1, respectively.]

Suitability requirements

Resolution: NLT 1.5 between travoprost and the 5,6-trans isomer

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of travoprost (C₂₆H₃₅F₃O₆) in the portion of Ophthalmic Solution taken:

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

r_U = peak response of travoprost from the Sample solution

r_S = peak response of travoprost from the Standard solution

C_S = concentration of USP Travoprost RSA (IRA 1-Sep-2020) in the Standard solution (mg/mL)

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

Acceptance criteria: 90.0%-110.0%

4 IMPURITIES

4.1 LIMIT OF TRAVOPROST RELATED COMPOUND A

Buffer: Add 1.0 mL of phosphoric acid to 1.0 L of water, and adjust with sodium hydroxide to a pH of 3.0.

Mobile phase: Acetonitrile and Buffer (6:19)

Standard solution: 0.3 µg/mL of USP Travoprost Related Compound A RS in a mixture of acetonitrile and water (1:4)

Sample solution: Use Ophthalmic Solution without dilution.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm x 5-cm; 3-µm packing L1

Flow rate: 3.0 mL/min

Injection volume: 100 µL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 10.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of travoprost related compound A in the portion of Ophthalmic Solution taken:

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

r_U = peak response of travoprost related compound A from the Sample solution

r_S = peak response of travoprost related compound A from the Standard solution

C_S = concentration of USP Travoprost Related Compound A RS in the Standard solution (mg/mL)

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

Acceptance criteria: NMT 1.0%

Change to read:

4.2 LIMIT OF DEGRADATION PRODUCTS

Buffer, Mobile phase, Standard solution, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each degradation product in the portion of Ophthalmic Solution taken:

                         Result = (r_U/r_S) × (C_S/C_U)× (1/F) × 100

r_U = peak response of each degradation product from the Sample solution

r_S = peak response of travoprost from the Standard solution 

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

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

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1.

Table 1

^▲a Isopropyl (E)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(R,E)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]but-1-enyi]cyclopentyl]hept-5-enoate.

^b Isopropyl (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E)-3-oxo-4-[3-(trifluoromethyl)phenoxy]but-1-enyl]cyclopentyl]hept-5-enoate. _{▲(IRA 1-Sep-2020)}

^c It is the sum of all degradation products, including travoprost related compound A, obtained in the test for Limit of Travoprost Related Compound A.

5 SPECIFIC TESTS

5.1 STERILITY TESTS (71)

Meets the requirements

Change to read:

5.2 pH (791)

Acceptance criteria: 5.5-6.5

^▲If labeled to contain polyquarternium-1 as a preservative: 6.4-7.0

If labeled to contain zinc chloride as an ingredient: 5.5-5.9_{▲(IRA 1-Sep-2020)}

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in tight containers. Store between 2° and 25°.

Add the following:

6.2 LABELING

If the Ophthalmic Solution is formulated with polyquarternium-1 as a preservative, it is so labeled. If the Ophthalmic Solution is formulated with zinc chloride as an ingredient, it is so labeled._{▲(IRA 1-Sep-2020)}

6.3 USP REFERENCE STANDARDS (11)

USP Travoprost RS

USP Travoprost Related Compound A RS

(5Z,13E)-(9S,11R,15R)-9,11,15-Trihydroxy-16-(m-trifluoromethylphenoxy)-17,18,19,20-tetranor-5,13-prostadienoic acid;

Also known as (Z)-7-((1R,2R,3R,5S)-3,5-Dihydroxy-2-((R,E)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]but-1-enyl)cyclopentyl) hept-5-enoic acid.

C₂₃H₂₉F₃O₆               458.47