Travoprost

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

C₂₆H₃₅F₃O₆               500.55

[1R-[1α(Z),2β(1E,3R*), 3α, 5α]]-7-[3,5-Dihydroxy-2-[3-hydroxy-4-[3-(trifluoromethyl)phenoxy]-1-butenyl] cyclopentyl]-5-heptenoic acid, 1-methylethyl ester,

Isopropyl (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3R)-3-hydroxy-4-[(α,α,α-trifluoro-m-tolyl)oxy]-1-butenyl] cyclopentyl)-5-heptenoate CAS RN^®:157283-68-6; UNII: WJ68R08KX9.

1 DEFINITION

Travoprost contains NLT 96.0% and NMT 102.0% of travoprost (C₂₆H₃₅F₃O₆), calculated on the anhydrous and solvent-free basis. 

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

2 IDENTIFICATION

2.1 A. THIN-LAYER CHROMATOGRAPHIC IDENTIFICATION TEST (201)

Standard solution: Use USP Travoprost RS.

Sample solution: Prepare as directed in the Assay.

Chromatographic system

Adsorbent: Chromatographic plate coated with silica gel that contains 20% silver nitrate

Application volume: 5 µL. [NOTE-To keep the spot size small, it is usually necessary to apply approximately 1-2 µL at a time, allowing the spot to dry between each application.]

Developing solvent system: Ethyl acetate and Ethanol (4:1)

Spray reagent: 20% phosphomolybdic acid in ethanol

Analysis

Samples: Standard solution and Sample solution

Proceed as directed in the chapter. Spray the plate with Spray reagent, and heat it in an oven at 80-100°. The travoprost will appear as black spots.

Acceptance criteria: Meets the requirements

2.2 B.

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

3 ASSAY

PROCEDURE

Buffer: Add 2.0 mL of phosphoric acid to 1 L of water. Adjust with sodium hydroxide to a pH of 3.0.

Mobile phase: Acetonitrile and Buffer (3:7)

Standard solution: Use USP Travoprost RS without dilution (0.5 mg/mL).

Sample solution: Transfer 25 mg of Travoprost to a 50-ml. volumetric flask, and dissolve in 15 mL of acetonitrile. Add 25 mL of water, mix, and wait until the solution reaches room temperature. Dilute with water to volume, and mix.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 220 nm

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

Flow rate: 3.0 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 about 1.0 and 1.1, respectively.]

Suitability requirements

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

Column efficiency: NLT 1500 theoretical plates

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of travoprost (C₂₆H₃₅F₃O₆) in the portion of Travoprost taken: 26 35

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

r_U = peak area from the Sample solution

r_S = peak area from the Standard solution

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

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

Acceptance criteria: 96.0%~102.0% on the anhydrous and solvent-free basis

4 IMPURITIES

4.1 ORGANIC IMPURITIES

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

Analysis

Sample: Sample solution

Calculate the percentage of each impurity in the portion of Travoprost taken:

                         Result = (r_U/r_T) x (1/F) x 100

r_U = peak response for each individual impurity

r_T = sum of the responses of all the peaks 

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1.

Table 1

^a (5Z)-(9S,11R,15S)-9,11,15-Trihydroxy-13,14-epoxy-16-(m-trifluoro methylphenoxy)-17,18,19,20-tetranor-5-prostadienoic acid, isopropyl ester.

^b (5Z,13E)-(95,11R,15S)-9,11,15-Trihydroxy-16-(m-trifluoromethyl phenoxy)-17,18,19,20-tetranor-5,13-prostadienoic acid, isopropyl ester.

^c (5E,13E)-(9S,11R,15R)-9,11,15-Trihydroxy-16-(m-trifluoromethyl phenoxy)-17,18,19,20-tetranor-5,13-prostadienoic acid, isopropyl ester.

^d (52,13E)-(9S,11R)-9,11-Dihydroxy-15-oxo-16-(m-trifluoromethyl phenoxy)-17,18,19,20-tetranor-5,13-prostadienoic acid, isopropyl ester.

4.2 LIMIT OF ETHYL ACETATE

Standard solution: 50 µg/mL of ethyl acetate in N,N-dimethylacetamide

Sample solution: 0.02 g/mL of Travoprost in N,N-dimethylacetamide

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: GC

Detector: Flame ionization

Column: 0.53 - mm x 30 - m 1-µm coating G16.

Carrier gas: Helium

Temperatures

Injector port: 140°

Detector: 240°

Column: See Table 2.

Table 2

Flow rate: 4 mL/min

Injection volume: 1 µL

System suitability

Sample: Standard solution

[NOTE-The retention time for ethyl acetate is about 2-5 min.]

Suitability requirements

Resolution: NLT 1.5 between ethyl acetate and any adjacent peak

Relative standard deviation: NMT 15.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration, in ppm, of ethyl acetate in the portion of Travoprost taken:

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of ethyl acetate in the Standard solution (µg/mL)

C_U = concentration of Travoprost in the Sample solution (g/mL)

Acceptance criteria: NMT 5000 ppm

5 SPECIFIC TESTS

5.1 OPTICAL ROTATION, Specific Rotation(7815)

Sample solution: 20 mg/mL in dehydrated alcohol

Acceptance criteria: +52.0° to +58.0° at 365 nm

5.2 WATER DETERMINATION, Method la(921)

Sample: 0.2 g

Solvent: Acetonitrile and methanol (1:1)

Titrant: Use a titrant for which 1 mL is equivalent to 2 mg of water.

Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve at -25° to 15° in tight, light-resistant containers under a nitrogen atmosphere.

USP REFERENCE STANDARDS (11)

USP Travoprost RS