Levocabastine Hydrochloride
(lee'' voe ka bas' teen hye'' droe klor' ide).
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C26H29FN2O2·HCl 456.98
4-Piperidinecarboxylic acid, 1-[4-cyano-4-(4-fluorophenyl)cyclohexyl]-3-methyl-4-phenyl-, monohydrochloride, (–)-[1(cis),3,4]-;    
(–)-trans-1-[cis-4-Cyano-4-(p-fluorophenyl)cyclohexyl]-3-methyl-4-phenylisonipecotic acid monohydrochloride     [79547-78-7].
Levocabastine Hydrochloride contains NLT 98.5% and NMT 101.5% of C26H29FN2O2·HCl, calculated on the dried basis.
•  B. Identification Tests—General, Chloride 191: Meets the requirements
•  C. Optical Rotation, Specific Rotation 781S: Meets the requirements
•  Procedure
Sample solution:  Dissolve 175 mg of Levocabastine Hydrochloride in 50 mL of alcohol, and add 5.0 mL of 0.01 N hydrochloric acid.
Titrimetric system 
Mode:  Direct titration
Titrant:  0.1 N sodium hydroxide VS
Endpoint detection:  Potentiometric
Sample:  Sample solution
The volume of titrant required to titrate Levocabastine Hydrochloride is the difference between the first and third endpoints. Perform a blank determination and make any necessary correction. Each mL of 0.1 N sodium hydroxide VS is equivalent to 22.85 mg of C26H29FN2O2·HCl.
Acceptance criteria:  98.5%–101.5% on the dried basis
Inorganic Impurities 
•  Residue on Ignition 281: NMT 0.1%, based on a sample weight of about 1.000 g
Organic Impurities 
•  Procedure
[Note—Prepare solutions immediately before use. ]
Diluent:  2 mg/mL of sodium hydroxide in water
Solution A:  Dissolve 1.39 g of boric acid in water, and adjust with 1 N sodium hydroxide to a pH of 9.0. Dilute with water to 100 mL.
Run buffer:  Dissolve 1.08 g of sodium dodecyl sulfate and 650 mg of hydroxypropyl--cyclodextrin in 5 mL of isopropyl alcohol, then dilute with Solution A to 50 mL.
System suitability solution:  12.5 µg/mL of USP Levocabastine Hydrochloride RS and 12.5 µg/mL of USP Levocabastine Related Compound A RS in Diluent
Standard solution:  Dilute 5.0 mL of the Sample solution with Diluent to 100 mL. Dilute 1.0 mL of this solution with Diluent to 10 mL to obtain a solution containing 12.5 µg/mL of Levocabastine Hydrochloride.
Sample solution:  2.5 mg/mL of Levocabastine Hydrochloride in Diluent
Capillary electrophoresis system 
Detector:  UV 214 nm
Column:  75-µm × 50-cm uncoated fused-silica capillary column
Column temperature:  50
Current:  See the gradient table below.
0 0
0.17 75
15 130
40 130
60 200
[Note—Before performing the System suitability, equilibrate the capillary column with Diluent for 2 min, then equilibrate with Run buffer for at least 5 min. ]
System suitability 
Sample:  System suitability solution
[Note—The relative migration times for levocabastine and levocabastine related compound A are approximately 1.0 and 1.07, respectively. ]
Suitability requirements 
Resolution:  NLT 4 between levocabastine and levocabastine related compound A
[Note—If necessary, adjust the current gradient to achieve the required resolution. ]
Samples:  Diluent (blank), Standard solution, and Sample solution
Separately inject equal volumes (pressure of 3450 Pa for 5 s) of the Samples, and record the peak responses.
[Note—Disregard any peak originating from the Diluent. Disregard any peak with an area of less than 0.1 times the major peak area of the Standard solution (0.05%). ]
Acceptance criteria:  The area for any peak in the Sample solution, other than the major peak, is not greater than the major peak area of the Standard solution (0.5%); and the sum of all peak areas in the Sample solution, except for the major peak, is not greater than twice the major peak area of the Standard solution (1.0%).
•  Optical Rotation, Specific Rotation 781S: –102 to 106 at 20
Sample solution:  10 mg/mL in methanol
•  Loss on Drying 731: Dry about 1.000 g of the sample at 105 to constant weight: it loses NMT 0.5% of its weight.
•  Packaging and Storage: Preserve in well-closed containers. Protect from light.
•  USP Reference Standards 11
USP Levocabastine Hydrochloride RS Click to View Structure
USP Levocabastine Related Compound A RS
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Mary S. Waddell
Scientific Liaison
(SM42010) Monographs - Small Molecules 4
Reference Standards RS Technical Services
USP35–NF30 Page 3664
Pharmacopeial Forum: Volume No. 36(1) Page 116