Olopatadine Hydrochloride Ophthalmic Solution
DEFINITION
Olopatadine Hydrochloride Ophthalmic Solution is a sterile aqueous solution of Olopatadine Hydrochloride. It contains NLT 90.0% and NMT 110.0% of the labeled amount of olopatadine (C21H23NO3). It may contain suitable antimicrobial agents.
IDENTIFICATION
• The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
[NoteProtect solutions 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 (7:18)
Standard solution:
0.1 mg/mL of USP Olopatadine Hydrochloride RS in Mobile phase
Sample solution:
Equivalent to 0.1 mg/mL of olopatadine in Mobile phase, from Olopatadine Hydrochloride Ophthalmic Solution
Chromatographic system
Mode:
LC
Detector:
UV 299 nm
Column:
4.6-mm × 15-cm; 5-µm packing L7
Flow rate:
1 mL/min
Injection size:
30 µL
System suitability
Sample:
Standard solution
Suitability requirements
Column efficiency:
NLT 2000 theoretical plates
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C21H23NO3 in the portion of Ophthalmic Solution taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
Acceptance criteria:
90.0%110.0%
IMPURITIES
Organic Impurities
[NoteProtect solutions from light. ]
• Procedure 1: Limit of Early Eluting Impurities
Mobile phase:
Proceed as directed in the Assay.
Blank solution:
Mobile phase
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
Standard solution:
0.2 mg/mL of USP Olopatadine Hydrochloride RS in Mobile phase
Sample solution:
Equivalent to 0.2 mg/mL of olopatadine in Mobile phase, from Olopatadine Hydrochloride Ophthalmic Solution
Chromatographic system
Mode:
LC
Detector:
UV 299 nm
Column:
4.6-mm × 15-cm; 5-µm packing L7
Flow rate:
1 mL/min
Injection size:
30 µL
Run time:
At least 1.6 times the retention time of the major peak
System suitability
Samples:
System suitability solution and Standard solution
Suitability requirements
Resolution:
NLT 2.0 between olopatadine and olopatadine related compound B, System suitability solution
Column efficiency:
NLT 2000 theoretical plates, Standard solution
Tailing factor:
NMT 2.0, Standard solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Ophthalmic Solution taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × (1/F) × 100
[NoteDisregard any peaks corresponding to those of the Blank solution and any peaks with relative retention time, measured with respect to olopatadine, greater than 1.5. ]
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Impurity Table 1
• Procedure 2: Limit of Late Eluting Impurities
Buffer:
Proceed as directed in the Assay.
Mobile phase:
Acetonitrile and Buffer (1:1)
Blank solution:
Mobile phase
System suitability solution:
0.02 mg/mL of USP Olopatadine Hydrochloride RS and 0.01 mg/mL of USP Olopatadine Related Compound C RS in Mobile phase
Standard solution:
0.01 mg/mL of USP Olopatadine Related Compound C RS in Mobile phase
Sample solution:
Use the Sample solution from the test for Limit of Early Eluting Impurities.
Chromatographic system
Mode:
LC
Detector:
UV 299 nm
Column:
4.6-mm × 15-cm; 5-µm packing L7
Flow rate:
1 mL/min
Injection size:
30 µL
Run time:
At least 3 times the retention time of the olopatadine related compound C peak
System suitability
Samples:
System suitability solution and Standard solution
[NoteThe relative retention times for olopatadine and olopatadine related compound C are 0.3 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 7.0 between olopatadine and olopatadine related compound C, System suitability solution
Column efficiency:
NLT 2000 theoretical plates, Standard solution
Tailing factor:
NMT 2.0, Standard solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Ophthalmic Solution taken:
Result = (rU/rS) × (CS/CU) × 100
[NoteDisregard any peaks corresponding to those of the Blank solution and any peaks with a relative retention time, measured with respect to olopatadine related compound C, less than 0.7. ]
Acceptance criteria
Individual impurities:
NMT 1% of olopatadine related compound C is found; and NMT 0.5% of any other individual impurity is found.
Total impurities:
NMT 3%. [NoteTotal impurities are the sum of olopatadine related compound B, olopatadine related compound C, Olopatadine E-isomer, Olopatadine carbaldehyde, and all other impurities found in the tests for Limit of Early Eluting Impurities and Limit of Late Eluting Impurities. ]
SPECIFIC TESTS
• Sterility Tests 71:
Meets the requirements
• pH 791:
Between 5.0 and 8.0
• Osmolality and Osmolarity 785:
Between 260 and 320 mOsmol/kg
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight, light-resistant containers. Store between 4 and 25.
• USP Reference Standards 11
USP Olopatadine Hydrochloride Related Compound B RS
(Z)-3-{2-(Carboxymethyl)dibenzo[b,e]oxepin-11(6H)-ylidene}-N,N-dimethylpropan-1-amine oxide. C21H23NO4 353.41
USP Olopatadine Hydrochloride Related Compound C RS
11-Oxo-6,11-dihydrodibenzo[b,e]oxepin-2-yl acetic acid. C16H12O4 268.26
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 4107
Pharmacopeial Forum: Volume No. 35(3) Page 568
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