Tropicamide

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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C₁₇H₂₀N₂O₂    284.35

Benzeneacetamide, N-ethyl-α-(hydroxymethyl)-N-(4-pyridinylmethyl)-, (±)-;

N-Ethyl-3-hydroxy-2-phenyl-N-(pyridin-4- ylmethyl)propanamide CAS RN: 1508-75-4; UNII: N0A3Z5XTC6.

1 DEFINITION

Tropicamide contains NLT 98.0% and NMT 102.0% of tropicamide (C₁₇H₂₀N₂O₂), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K _{(CN 1-MAY-2020)}

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: Dissolve 0.135 g of sodium dodecyl sulfate and 3.4 mL of phosphoric acid in 950 mL of water. Adjust with 10 M sodium hydroxide to a pH of 3.0, and dilute with water to 1000 mL.

Mobile phase: Acetonitrile and Buffer (27:73)

Standard solution: 0.15 mg/mL of USP Tropicamide RS prepared as follows. Transfer USP Tropicamide RS into a suitable volumetric flask, and add acetonitrile equivalent to 6% of the final volume to dissolve. Dilute with water to volume.

Sample solution: 0.15 mg/mL of Tropicamide prepared as follows. Transfer Tropicamide into a suitable volumetric flask, and add acetonitrile equivalent to 6% of the final volume to dissolve. Dilute with water to volume.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: 210 nm

Column: 4.6-mm x 15-cm; 3-µm packing L1

Column temperature: 40°

Flow rate: 0.8 mL/min

Injection volume: 15 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of tropicamide (C₁₇H₂₀N₂O₂) in the portion of Tropicamide taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of tropicamide from the Sample solution

r_s = peak response of tropicamide from the Standard solution

C_s = concentration of USP Tropicamide RS in the Standard solution (mg/mL)

C_u = concentration of Tropicamide in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the dried basis

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

5 ORGANIC IMPURITIES

Buffer and Mobile phase: Proceed as directed in the Assay.

System suitability stock solution 1: 100 µg/mL each of USP Tropicamide Related Compound A RS, USP Tropicamide Related Compound C RS, and USP Tropicamide Related Compound D RS prepared as follows. Transfer USP Tropicamide Related Compound A RS, USP Tropicamide Related Compound C RS, and USP Tropicamide Related Compound D RS into a suitable volumetric flask, and add acetonitrile equivalent to 4% of the final volume to dissolve. Dilute with water to volume..

System suitability stock solution 2: 10 µg/ml. each of USP Tropicamide Related Compound A RS, USP Tropicamide Related Compound C RS, and USP Tropicamide Related Compound D RS prepared as follows. Dilute 1 mL of System suitability stock solution 1 with water to 10 mL...

System suitability stock solution 3: 0.5 mg/mL of USP Tropicamide RS and 20 µg/mL of USP Tropicamide Related Compound B RS prepared as follows. Transfer USP Tropicamide RS and USP Tropicamide Related Compound B RS into a suitable volumetric flask, and add acetonitrile equivalent to 10% of the final volume to dissolve. Dilute with water to volume.

System suitability solution: Mix 1 mL each of System suitability stock solution 2 and System suitability stock solution 3.

Standard stock solution: 1 mg/mL of USP Tropicamide RS prepared as follows. Transfer USP Tropicamide RS into a suitable volumetric flask, and add acetonitrile equivalent to 6% of the final volume to dissolve. Dilute with water to volume.

Standard solution 1: 1 µg/mL of USP Tropicamide RS in water from Standard stock solution

Standard solution 2: 1.5 µg/mL each of USP Tropicamide Related Compound C. RS and USP Tropicamide Related Compound D RS in water from System suitability stock solution 1

Sample solution: 1 1 mg/mL of Tropicamide prepared as follows. Transfer 50 mg of Tropicamide into a 50-mL volumetric flask, and add 3 mL of acetonitrile to dissolve. Dilute with water to volume.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: 210 and 254 nm

Column: 4.6-mm x 15-cm; 3-µm packing L1

Column temperature: 40°

Flow rate: 0.8 mL/min

Injection volume: 15 µL

Run time: NLT 3 times the retention time of the tropicamide peak

System suitability

Sample: System suitability solution

Suitability requirements

Resolution at 210 nm: NLT 2 between the tropicamide related compounds C and A peaks; NLT 2 between the tropicamide related compounds A and D peaks

Analysis

Samples: Standard solution 1, Standard solution 2, and Sample solution

Calculate the percentage of tropicamide related compound C and tropicamide related compound D in the portion of Tropicamide taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of relevant tropicamide related compound from the Sample solution at 210 nm

r_s = peak response of relevant tropicamide related compound from Standard solution 2 at 210 nm

C_s = concentration of relevant tropicamide related compound in Standard solution 2 (mg/mL)

C_u = concentration of Tropicamide in the Sample solution (mg/mL)

Calculate the percentage of other individual impurities in the portion of Tropicamide taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (1/F) × 100

r_u = peak response of each impurity from the Sample solution at 254 nm

r_s = peak response of USP Tropicamide RS from Standard solution 1 at 254 nm

C_s = concentration of USP Tropicamide RS in Standard solution 1 (mg/mL)

C_u = concentration of Tropicamide in the Sample solution (mg/mL)

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

Acceptance criteria: See Table 1. Disregard any impurity peaks less than 0.05% at 254 nm.

Table 1

^a Excluding tropicamide related compound C and tropicamide related compound D.

6 SPECIFIC TESTS

Loss on Drying 〈731〉

Sample: 500 mg

Analysis: Dry the Sample under vacuum over phosphorus pentoxide at 80° for 4 h.

Acceptance criteria: NMT 0.5%

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers.

USP Reference Standards 〈11〉

USP Tropicamide RS

USP Tropicamide Related Compound A RS

N-(Pyridin-4-ylmethyl)ethanamine.

C₈H₁₂N₂ 136.19

USP Tropicamide Related Compound B RS

N-Ethyl-2-phenyl-N-(pyridin-4-ylmethyl)acrylamide.

C₁₇H₁₈N₂O 266.34

USP Tropicamide Related Compound C RS

3-Hydroxy-2-phenylpropionic acid.

C₉H₁₀O₃ 166.17

USP Tropicamide Related Compound D RS

2-Phenylacetic acid.

C₈H₈O₂ 136.15