Lansoprazole
(lan soe' pra zole).
Click to View Image

C16H14F3N3O2S 369.36
1H-Benzimidazole, 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-;    
2-[[[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]-methyl]sulfinyl]benzimidazole     [103577-45-3].
DEFINITION
Lansoprazole contains NLT 98.0% and NMT 102.0% of C16H14F3N3O2S.
IDENTIFICATION
•  B. Ultraviolet Absorption 197U
Sample solution:  10 µg/mL in methanol
Acceptance criteria:  Meets the requirements
ASSAY
Change to read:
•  Procedure
Mobile phase:  Acetonitrile, water, and triethylamine (40:60:1). Adjust with phosphoric acid to a pH of 7.0.
Diluent:  Acetonitrile, water, and triethylamine (40:60:1). Adjust with phosphoric acid to a pH of 10.0.
USP35
System suitability solution:  0.1 mg/mL of USP Lansoprazole RS and 0.1 mg/mL of USP Lansoprazole Related Compound A RS in Diluent
Standard solution:  0.1 mg/mL of USP Lansoprazole RS in DiluentUSP35
Sample solution:  0.1 mg/mL of Lansoprazole in DiluentUSP35
Chromatographic system 
Mode:  LC
Detector:  UV 285 nm
Column:  4.6-mm × 25-cm; 5-µm packing L1
Flow rate:  1 mL/min
Injection size:  10 µL
System suitability 
Samples:  System suitability solution and Standard solution
Suitability requirements 
Resolution:  NLT 5 between lansoprazole and lansoprazole related compound A, System suitability solution
Relative standard deviation:  NMT 1.0%, Standard solution
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of lansoprazole (C16H14F3N3O2S) in the portion of Lansoprazole taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response from the Sample solution
rS== peak response from the Standard solutionUSP35
CS== concentration of USP Lansoprazole RS in the Standard solution (mg/mL)
CU== concentration of Lansoprazole in the Sample solution (mg/mL)
Acceptance criteria:  98.0%–102.0%
IMPURITIES
Inorganic Impurities 
•  Residue on Ignition 281: NMT 0.1%
Change to read:
Organic Impurities 
•  Procedure
[Note—Store and inject the lansoprazole solutions at or below 5 using a cooled autosampler. The solutions are stable for about 24 h when stored at 5. ]
Solution A:  Water
Solution B:  Acetonitrile, water, and triethylamine (160:40:1). Adjust with phosphoric acid to a pH of 7.0.
Diluent:  Methanol and 0.1 N sodium hydroxide (1:3)
Mobile phase:  See Table 1.
Table 1
Time
(min)
Solution A
(%)
Solution B
(%)
0 90 10
40 20 80
50 20 80
51 90 10
60 90 10
System suitability solution:  Prepare a solution containing 25 µg/mL of USP Lansoprazole RS and 25 µg/mL of USP Lansoprazole Related Compound A RS in methanol. Transfer 1 mL of this solution into a 10-mL volumetric flask, and dilute with Diluent to volume.
USP35
Standard solution:  Prepare a solution containing 25 µg/mL of USP Lansoprazole RS and 25 µg/mL of USP Lansoprazole Related Compound B RSUSP35 in methanol. Transfer 1 mL of this solution into a 100-mLUSP35 volumetric flask, and dilute with Diluent to volume.
Sample solution:  2.5 mg/mL of Lansoprazole in methanol. Transfer 1 mL of this solution into a 10-mL volumetric flask, and dilute with Diluent to volume.
Blank:  Methanol and Diluent (1:9)
Chromatographic system 
Mode:  LC
Detector:  UV 285 nm
Column:  4.6-mm × 15-cm; 5-µm packing L1
Flow rate:  0.8 mL/min
Injection size:  40 µL
System suitability 
Sample:  System suitability solution USP35
Suitability requirements 
Resolution:  NLT 6 between lansoprazole and lansoprazole related compound A USP35
Relative standard deviation:  NMT 3% USP35
Analysis 
Samples:  Standard solution, Sample solution, and Blank
Identify the lansoprazole peak and the peaks due to the impurities listed in Table 2. Measure the areas for the major peaks, excluding peaks obtained from the Blank.
Calculate the percentage of lansoprazole related compound B in the portion of Lansoprazole taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response for lansoprazole related compound B from the Sample solution
rS== peak response for lansoprazole related compound B from the Standard solution
CS== concentration of USP Lansoprazole Related Compound B RS in the Standard solution (µg/mL)
CU== concentration of Lansoprazole in the Sample solution (µg/mL)
USP35
Calculate the percentage of lansoprazole N-oxide, lansoprazole sulfone, and any other individualUSP35 impurity in the portion of Lansoprazole taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
rU== peak response for each impurity from the Sample solution
rS== peak response for lansoprazole from the Standard solution
CS== concentration of USP Lansoprazole RS in the Standard solution (µg/mL)
CU== concentration of Lansoprazole in the Sample solution (µg/mL)
F== relative response factor for each impurity (see Table 2)
Acceptance criteria 
Individual impurities:  See Table 2. Disregard any peak below 0.05%.USP35
Table 2
Name Relative
Retention
Time
Relative
Response
Factor
Acceptance
Criteria,
NMT (%)
Lansoprazole
N-oxidea
0.8 1.3 0.1
Lansoprazole 1.0
Lansoprazole related compound A (lansoprazole sulfone)b 1.1 0.82 0.4
Lansoprazole related compound BUSP35 (lansoprazole sulfide)c 1.2 USP35 0.1
Other individual
impurity
1.00 0.1
Total impurities 0.6
a  [[(1H-Benzimidazole-2-yl)sulfinyl]methyl]-3-methyl-4-(2,2,2-trifluoroethoxy)-pyridine 1-oxide.
b  2-[[[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfonyl]benzimidazole.
c  2-[[[3-Methyl-4-(2,2,2-trifluoroethoxy)-pyridin-2-yl]methyl]sulfanyl]-1H-benzimidazole.
SPECIFIC TESTS
•  Water Determination, Method Ia 921
Sample:  1.0 g
[Note—Use 50 mL of a dehydrated mixture of pyridine and ethylene glycol (9:1 to 8:2) as the solvent. ]
Acceptance criteria:  NMT 0.1%
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in tight, light-resistant containers. Store at room temperature, and protect from excessive heat.
Change to read:
•  USP Reference Standards 11
USP Lansoprazole RS Click to View Structure
USP Lansoprazole Related Compound A RS
2-[[[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfonyl]benzimidazole.
    C16H14F3N3O3S        385.36
USP Lansoprazole Related Compound B RS
2-[[[3-Methyl-4-(2,2,2-trifluoroethoxy)-pyridin-2-yl]methyl]sulfanyl]-1H-benzimidazole.
    C16H14F3N3OS        353.36
USP35
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USP35–NF30 Page 3642
Pharmacopeial Forum: Volume No. 36(6) Page 1547