Pilocarpine Hydrochloride
(pye'' loe kar' peen hye'' droe klor' ide).
C11H16N2O2·HCl 244.72 2(3H)-Furanone, 3-ethyldihydro-4-[(1-methyl-1H-imidazol-5-yl)methyl]-, monohydrochloride, (3S-cis)-; Pilocarpine monohydrochloride [54-71-7]. DEFINITION
Pilocarpine Hydrochloride contains NLT 98.0% and NMT 102.0% of C11H16N2O2·HCl, calculated on the dried basis.
IDENTIFICATION
ASSAY
• Procedure
Buffer:
4.4 g/L of dibasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 6.5 ± 0.1.
Mobile phase:
Acetonitrile, methanol, and Buffer (2:35:63)
Standard solution:
0.5 mg/mL of USP Pilocarpine Hydrochloride RS in water. [NoteSonicate if necessary. ]
System suitability solution:
Transfer a known quantity of USP Pilocarpine Hydrochloride RS in a suitable volumetric flask, and add water, equivalent to 10% of the volume of the flask, to dissolve. [NoteSonicate as needed. ] Add 0.1 N sodium hydroxide, equivalent to 10% of the volume of the flask, quench immediately with the same volume of 0.1 N hydrochloric acid, and mix. Dilute with water to volume. [NoteThe initial concentration of USP Pilocarpine Hydrochloride RS is 0.5 mg/mL. Isopilocarpine is formed in the System suitability solution preparation. ]
Sample solution:
0.5 mg/mL of Pilocarpine Hydrochloride in water. [NoteSonicate if necessary. ]
Chromatographic system
Mode:
LC
Detector:
UV 215 nm
Column:
4.6-mm × 15-cm; 3-µm packing L11
Column temperature:
35
Flow rate:
1.0 mL/min
Injection size:
10 µL
System suitability
Samples:
Standard solution and System suitability solution
Suitability requirements
Resolution:
NLT 1.5 between isopilocarpine and pilocarpine, System suitability 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 C11H16N2O2·HCl in the portion of Pilocarpine Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria:
98.0%102.0% on the dried basis
IMPURITIES
Organic Impurities
• Procedure 1: Related Compounds
Mobile phase, Standard solution, System suitability solution, and Sample solution:
Proceed as directed in the Assay.
Sensitivity solution:
0.25 µg/mL of USP Pilocarpine Hydrochloride RS in water from the Standard solution
Chromatographic system
Mode:
LC
Detector:
UV 215 nm
Column:
4.6-mm × 15-cm; 3-µm packing L11
Column temperature:
35
Flow rate:
1.0 mL/min
Run time:
NLT 5 times the retention time of the pilocarpine peak
Injection size:
10 µL
System suitability
Samples:
Standard solution, System suitability solution, and Sensitivity solution
Suitability requirements
Resolution:
NLT 1.5 between isopilocarpine and pilocarpine, System suitability solution
Signal-to-noise ratio:
NLT 10 for the pilocarpine peak, Sensitivity solution
Relative standard deviation:
NMT 2.0% for the pilocarpine peak, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Pilocarpine Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria
Individual impurities:
See Impurity Table 1. [NoteDisregard any unspecified impurity peaks less than 0.05%. ]
Total impurities:
NMT 1.0%
Impurity Table 1
• Procedure 2: Other Alkaloids
Sample solution:
10 mg/mL in water
Analysis:
Divide the Sample solution into two portions. To one portion add a few drops of 6 N ammonium hydroxide, and to the other, add a few drops of potassium dichromate TS.
Acceptance criteria:
No turbidity is produced in either solution.
SPECIFIC TESTS
• Loss on Drying 731:
Dry a sample at 105 for 2 h: it loses NMT 3.0% of its weight.
• Readily Carbonizable Substances Test 271
Sample solution:
50 mg/mL in sulfuric acid
Acceptance criteria:
The solution has no more color than Matching Fluid B.
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight, light-resistant containers. Store at room temperature.
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 4322
Pharmacopeial Forum: Volume No. 35(6) Page 1473
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