Latanoprost

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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C₂₆H₄₀O₅ 432.60 (USP 1-Dec-2022)

5-Heptenoic acid, 7-[3,5-dihydroxy-2-(3-hydroxy-5-phenylpentyl)cyclopentyl]-1-methylethyl ester, [1R-[1α(Z),2β(R*),3α,5α]]-;

Isopropyl (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]-5-heptenoate CAS RN®: 130209-82-4; UNII: 6Z5B6HVF6O.

1 DEFINITION

Latanoprost contains NLT 94.0% and NMT 102.0% of latanoprost (C₂₆H₄₀O₅ ), calculated on the anhydrous and solvent-free basis.

[Caution—Wear protective glasses and gloves while handling the material. Avoid contact during pregnancy or while nursing.]

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197F or 197A (USP 1-Dec-2022)

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

Change to read:

Procedure

Mobile phase: Chromatographic hexane and dehydrated alcohol (94:6)

System suitability solution: 2.0 mg/mL of USP Latanoprost RS and 20 μg/mL of USP Latanoprost Related Compound A RS prepared as follows. Transfer USP Latanoprost RS and USP Latanoprost Related Compound A RS into a suitable volumetric flask, dissolve in dehydrated alcohol equivalent to 20% of the final volume, and dilute with chromatographic hexane to volume.

Standard solution: 2.0 mg/mL of USP Latanoprost RS prepared as follows. Transfer USP Latanoprost RS into a suitable volumetric flask, dissolve in dehydrated alcohol equivalent to 20% of the final volume, and dilute with chromatographic hexane to volume. (ERR 1-Dec-2022)

Sample solution: 2.0 mg/mL of Latanoprost prepared as follows. Transfer Latanoprost into a suitable volumetric flask, dissolve in dehydrated alcohol equivalent to 20% of the final volume, and dilute with chromatographic hexane to volume. (ERR 1-Dec-2022)

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.0-mm × 25-cm; 5-μm packing L3

Temperatures

Autosampler: 5° (USP 1-Dec-2022)

Column: 30°

Flow rate: 1 mL/min

Injection volume: 10 μL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for latanoprost and latanoprost related compound A are 1.0 and 1.1, respectively.]

Suitability requirements

Resolution: NLT 2.0 between latanoprost and latanoprost related compound A, System suitability solution

Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of latanoprost (C₂₆H₄₀O₅) in the portion of Latanoprost taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak area of latanoprost (USP 1-Dec-2022) from the Sample solution

r_S = peak area of latanoprost (USP 1-Dec-2022) from the Standard solution

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

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

Acceptance criteria: 94.0%–102.0% on the anhydrous and solvent-free basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.50%

Change to read:

Organic Impurities

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

Standard stock solution: 0.3 mg/mL of USP Orlistat Related Compound C RS in a mixture of chromatographic hexane and dehydrated alcohol (80:20) prepared as follows. Transfer USP Orlistat Related Compound C RS into a suitable volumetric flask, dissolve in dehydrated alcohol equivalent to 20% of the final volume, and dilute with chromatographic hexane to volume. (USP 1-Dec-2022)

Standard solution: 0.04 mg/mL of USP Latanoprost RS and 0.003 mg/mL of USP Orlistat Related Compound C RS (USP 1-Dec-2022) in a mixture of chromatographic hexane and dehydrated alcohol (80:20) prepared as follows. Transfer USP Latanoprost RS into a suitable volumetric flask, dissolve in dehydrated alcohol equivalent to 20% of the final volume, add a suitable amount of the Standard stock solution, (USP 1-Dec-2022) and dilute with chromatographic hexane to volume.

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2.0 between latanoprost and latanoprost related compound A, System suitability solution

Relative standard deviation: NMT 5.0% for latanoprost and orlistat related compound C, (USP 1-Dec-2022) Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of orlistat related compound C in the portion of Latanoprost taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak area of orlistat related compound C from the Sample solution

r_S = peak area of orlistat related compound C from the Standard solution

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

C_U = concentration of Latanoprost in the Sample solution (mg/mL) (USP 1-Dec-2022)

Calculate the percentage of any other (USP 1-Dec-2022) impurity in the portion of Latanoprost taken:

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

r_U = peak area of any other (USP 1-Dec-2022) impurity from the Sample solution

r_S = peak area of latanoprost from the Standard solution

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

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

F = relative response factor for each individual impurity (see Table 1)

Acceptance criteria: See Table 1. The reporting threshold is (USP 1-Dec-2022) 0.05%.

Table 1

^a Isopropyl 5-(diphenylphosphoryl)pentanoate.

^b Isopropyl (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3S)-3-hydroxy-5-phenylpentyl]cyclopentyl]-5-heptenoate.

^c Latanoprost related compound A and latanoprost related compound B are excluded.

Limit of Latanoprost Related Compound E

Solution A: Acetonitrile, phosphoric acid, and water (300:1:700)

Solution B: Acetonitrile, phosphoric acid, and water (800:1:200)

Mobile phase: See Table 2.

Table 2

Diluent: Acetonitrile and water (30:70)

Standard solution: 1.0 μg/mL of USP Latanoprost Related Compound E RS in Diluent

Sample solution: 1.0 mg/mL of Latanoprost in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 200 nm

Column: 4.0-mm × 15-cm; 5-μm packing L1

Column temperature: 60°

Flow rate: 1.0 mL/min

Injection volume: 50 μL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 5.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of latanoprost related compound E in the portion of Latanoprost taken:

Result = (r_U/r_S)x(C_S/C_U) × 100

r_U = peak area of latanoprost related compound E from the Sample solution

r_S = peak area of latanoprost related compound E from the Standard solution

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

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

Acceptance criteria: NMT 0.2%

5 SPECIFIC TESTS

Optical Rotation 〈781S〉, Procedures, Specific Rotation

Sample solution: 10 mg/mL of Latanoprost in acetonitrile

Acceptance criteria: +31° to +38°

Change to read:

Water Determination 〈921〉, Method I, Method Ic, or Method Ia (USP 1-Dec-2022)

Sample solution: 100 mg/mL of Latanoprost in ethyl acetate

(USP 1-Dec-2022)

Acceptance criteria: NMT 2.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed, light-resistant containers, and store in a refrigerator or a freezer.

Change to read:

USP Reference Standards 〈11〉

USP Latanoprost RS

USP Latanoprost Related Compound A RS

Isopropyl (E)-7-{(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl}-5-heptenoate.

C₂₆H₄₀O₅ 432.59

USP Latanoprost Related Compound E RS

(Z)-7-{(1R,2R,3R,5S)-3,5-Dihydroxy-2-[(R)-3-hydroxy-5-phenylpentyl]cyclopentyl}-5-heptenoic acid.

C₂₃H₃₄O₅ 390.51

USP Orlistat Related Compound C RS

Triphenyl phosphine oxide

C₁₈H₁₅OP 278.28 (USP 1-Dec-2022)