Olopatadine Hydrochloride

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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C₂₁H₂₃NO₃.HCl 373.87 

Dibenz[b,e]oxepin-2-acetic acid, 11-[3-(dimethylamino)propylidene]-6,11-dihydro-, hydrochloride, (Z)-; 

11-[(Z)-3-(Dimethylamino)propylidene]-6,11-dihydrodibenzo[b,e]oxepin-2-acetic acid, hydrochloride CAS RN®: 140462-76-6; UNII: 

1 DEFINITION 

Olopatadine Hydrochloride contains NLT 98.0% and NMT 102.0% of olopatadine hydrochloride (C₂₁H₂₃NO₃), calculated on the dried basis.

2 IDENTIFICATION 

Change to read: 

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197A or 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. C. Identification Tests—General 〈191〉, Chloride: Meets the requirements 

3 ASSAY 

Procedure 

Protect all solutions containing olopatadine hydrochloride from light. 

Buffer: Dissolve 13.6 g of monobasic potassium phosphate in 1 L of water, add 1 mL of triethylamine, and mix. Adjust with phosphoric acid to a pH of 3.0. 

Mobile phase: Acetonitrile and Buffer (28:72) 

Standard solution: 0.1 mg/mL of USP Olopatadine Hydrochloride RS in Mobile phase 

Sample solution: 0.1 mg/mL of Olopatadine Hydrochloride in Mobile phase 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 299 nm 

Column: 4.6-mm × 15-cm; 5-µm packing L7 

Flow rate: 1 mL/min 

Injection volume: 30 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 olopatadine hydrochloride (C₂₁H₂₃NO₃) in the portion of Olopatadine Hydrochloride 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 Olopatadine Hydrochloride RS in the Standard solution (mg/mL) 

C_U = concentration of Olopatadine Hydrochloride 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% 

Organic Impurities 

Protect all solutions containing olopatadine hydrochloride from light. 

Mobile phase: Prepare as directed in the Assay. 

System suitability solution: 0.2 mg/mL of USP Olopatadine Hydrochloride RS and 0.02 mg/mL of USP Olopatadine Related Compound B RS in Mobile phase 

Sample solution: 0.2 mg/mL of Olopatadine Hydrochloride in Mobile phase 

Blank solution: Mobile phase 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 299 nm 

Column: 4.6-mm × 15-cm; 5-µm packing L7 

Flow rate: 1 mL/min 

Injection volume: 30 µL 

Run time: At least 2.5 times the retention time of the major peak 

System suitability 

Sample: System suitability solution 

[Note—The relative retention times for olopatadine and olopatadine related compound B are 1.0 and 1.2, respectively.] Suitability requirements 

Resolution: NLT 2.0 between olopatadine and olopatadine related compound B 

Relative standard deviation: NMT 2.0%, olopatadine peak 

Analysis 

Sample: Sample solution 

Calculate the percentage of each impurity in the portion of Olopatadine Hydrochloride taken: 

Result = (r_U/r_T) × (1/F) × 100 

r_U = peak response of each individual impurity from the Sample solution 

r_T = sum of all the peak responses from the Sample solution 

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

Acceptance criteria 

Individual impurities: See Table 1. Disregard any peaks corresponding to those of the Blank solution, and any peak less than 0.05%. Table 1 

^a(Z)-2-{11-[3-(Dimethylamino)propylidene]-6,11-dihydrodibenzo[b,e]oxepin-2-yl}-2-hydroxyacetic acid.

^b 11-[(E)-3-(Dimethylamino)propylidene]-6,11-dihydrodibenzo[b,e]oxepin-2-acetic acid. 

5 SPECIFIC TESTS 

pH 〈791〉 

Sample: 10 mg/mL of Olopatadine Hydrochloride in water 

Acceptance criteria: 2.0–4.0 

Loss on Drying 〈731〉 

Analysis: Dry at 105° for 3 h. 

Acceptance criteria: NMT 0.3% 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in tight, light-resistant containers and store at room temperature. 

USP Reference Standards 〈11〉 USP Olopatadine Hydrochloride RS USP Olopatadine Related Compound B RS 

(Z)-3-{2-(Carboxymethyl)dibenzo[b,e]oxepin-11(6H)-ylidene}-N,N-dimethylpropan-1-amine oxide. 

C₂₁H₂₃NO₄ 353.41