Mefloquine Hydrochloride
(me' floe kwin hye'' droe klor' ide).
Click to View Image

C17H16F6N2O·HCl 414.77
4-Quinolinemethanol, -2-piperidinyl-2,8-bis(trifluoromethyl)-, monohydrochloride, (R*,S*)- (±)-;    
dl-erythro--2-Piperidyl-2,8-bis(trifluoromethyl)-4-quinolinemethanol monohydrochloride     [51773-92-3].
DEFINITION
Mefloquine Hydrochloride contains NLT 98.0% and NMT 102.0% of C17H16F6N2O·HCl, calculated on the anhydrous basis.
IDENTIFICATION
ASSAY
•  Procedure
Solution A:  1.5 g/L of sodium hydrogen sulfate in water
Mobile phase:  Dissolve 1 g of tetraheptylammonium bromide in a 1000-mL mixture of acetonitrile, methanol, and Solution A (2:1:2).
System suitability solution:  4 µg/mL each of USP Mefloquine Hydrochloride RS and USP Mefloquine Related Compound A RS in Mobile phase
Standard solution:  0.2 mg/mL of USP Mefloquine Hydrochloride RS in Mobile phase
Sample solution:  0.2 mg/mL of Mefloquine Hydrochloride in Mobile phase
Chromatographic system 
Mode:  LC
Detector:  UV 280 nm
Guard column:  4-mm × 3-cm; C18 (recommended)
Column:  4.0-mm × 25-cm; 5-µm packing L1
Column temperature:  25
Flow rate:  0.8 mL/min
Injection size:  20 µL
System suitability 
Samples:  System suitability solution and Standard solution
[Note—The relative retention times for mefloquine related compound A and mefloquine are about 0.7 and 1.0, respectively. ]
Suitability requirements 
Resolution:  NLT 2.0 between mefloquine related compound A and mefloquine, System suitability solution
Tailing factor:  NMT 2.0, Standard solution
Relative standard deviation:  NMT 1.0%, Standard solution
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of mefloquine hydrochloride (C17H16F6N2O·HCl) in the portion of Mefloquine Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response of mefloquine from the Sample solution
rS== peak response of mefloquine from the Standard solution
CS== concentration of USP Mefloquine Hydrochloride RS in the Standard solution (mg/mL)
CU== concentration of Mefloquine Hydrochloride in the Sample solution (mg/mL)
Acceptance criteria:  98.0%–102.0% on the anhydrous basis
IMPURITIES
•  Residue on Ignition 281: NMT 0.1%
•  Heavy Metals, Method II 231: NMT 20 ppm
•  Organic Impurities
Mobile phase:  Dissolve 1 g of tetraheptylammonium bromide in a 1-L mixture of a 1.5-g/L solution of sodium hydrogen sulfate, acetonitrile, and methanol (2:2:1).
System suitability solution:  4 µg/mL each of USP Mefloquine Hydrochloride RS and USP Mefloquine Related Compound A RS in Mobile phase. [Note—Mefloquine related compound A is threo-mefloquine. ]
Sample stock solution:  4 mg/mL of Mefloquine Hydrochloride in Mobile phase
Sample solution:  4 µg/mL from the Sample stock solution in Mobile phase
Chromatographic system 
Mode:  LC
Detector:  UV 280 nm
Guard column:  4-mm × 2.5-cm; 5-µm packing L1
Column:  4.0-mm × 25-cm; 5-µm packing L1
Flow rate:  0.8 mL/min
Injection size:  20 µL. [Note—Equilibrate the column with Mobile phase at a flow rate of 0.8 mL/min for 30 min. ]
System suitability 
Sample:  System suitability solution
[Note—The relative retention times for mefloquine related compound A and mefloquine are about 0.7 and 1.0, respectively. ]
Suitability requirements 
Resolution:  NLT 2.0 between mefloquine related compound A and mefloquine
Relative standard deviation:  NMT 2.0%
Analysis 
Samples:  Sample stock solution and Sample solution
Record the chromatogram for a time that is 10 times the retention time of the main peak.
Acceptance criteria:  The response of the mefloquine related compound A peak in the Sample stock solution is NMT twice the area of the main peak of the Sample solution (0.2%). The response of any other individual peak, other than the main peak of the Sample stock solution, is NMT that of the main peak of the Sample solution (0.1%); and the sum of the responses of any such peaks of the Sample stock solution is NMT five times the response of the main peak of the Sample solution (0.5%). [Note—Exclude the main peak and any other peak producing a response of less than 0.2 times (0.02%) the main peak of the Sample solution. ]
SPECIFIC TESTS
•  Optical Rotation, Specific Rotation 781S
Sample solution:  50 mg/mL in methanol
Acceptance criteria:  –0.2 to +0.2
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in tight, light-resistant containers. Store between 15 and 30.
•  USP Reference Standards 11
USP Mefloquine Hydrochloride RS Click to View Structure
USP Mefloquine Related Compound A RS
threo-Mefloquine.
    C17H16F6N2O·HCl        414.78
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Leonel M. Santos, Ph.D.
Senior Scientific Liaison
1-301-816-8168
(SM12010) Monographs - Small Molecules 1
Reference Standards RS Technical Services
1-301-816-8129
rstech@usp.org
USP35–NF30 Page 3783
Pharmacopeial Forum: Volume No. 35(5) Page 1160