Midodrine Hydrochloride
(mye' doe dreen hye'' droe klor' ide).
C12H18N2O4·HCl 290.74 Acetamide, 2-amino-N-[2-(2,5-dimethoxyphenyl)-2-hydroxyethyl]-, monohydrochloride, (±)-; (±)-2-Amino-N-(-hydroxy-2,5-dimethoxyphenethyl)acetamide monohydrochloride [3092-17-9]. DEFINITION
Midodrine Hydrochloride contains NLT 98.0% and NMT 102.0% of midodrine hydrochloride (C12H18N2O4·HCl), calculated on the anhydrous basis.
IDENTIFICATION
• B.
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
• C. Identification TestsGeneral, Chloride 191:
A 10 mg/mL solution of Midodrine Hydrochloride in water meets the requirements.
ASSAY
• Procedure
Buffer:
13.6 g/L of monobasic potassium phosphate. Adjust with phosphoric acid to a pH of 4.00 ± 0.05.
Mobile phase:
Acetonitrile and Buffer (3:22)
Standard solution:
0.05 mg/mL of USP Midodrine Hydrochloride RS in Mobile phase
Sample solution:
0.05 mg/mL of Midodrine Hydrochloride in Mobile phase
Chromatographic system
Mode:
LC
Detector:
UV 290 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Flow rate:
1 mL/min
Injection size:
20 µL
System suitability
Sample:
Standard solution
Suitability requirements
Column efficiency:
NLT 3000 theoretical plates
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C12H18N2O4·HCl in the portion of Midodrine Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria:
98.0%102.0% on the anhydrous basis
IMPURITIES
Inorganic Impurities
• Residue on Ignition 281:
NMT 0.2%. A 1-g sample is used.
• Heavy Metals, Method II 231:
NMT 10 ppm
Organic Impurities
• Procedure
Buffer and Mobile phase:
Proceed as directed in the Assay.
Standard solution:
1.0 µg/mL of USP Midodrine Hydrochloride RS and 2.0 µg/mL of USP Midodrine Related Compound A RS in Mobile phase
Sample solution:
1.0 mg/mL of Midodrine Hydrochloride in Mobile phase
Chromatographic system:
Proceed as directed in the Assay except for the following:
Injection size:
50 µL
System suitability
Sample:
Standard solution
Suitability requirements
Resolution:
NLT 2.0 between midodrine hydrochloride and midodrine hydrochloride related compound A
Tailing factor:
NMT 2.0 for midodrine hydrochloride
Relative standard deviation:
NMT 2.0% for both midodrine hydrochloride and midodrine related compound A
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of midodrine related compound A in the portion of Midodrine Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × 100
Calculate the percentage of any individual impurity in the portion of Midodrine Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria:
See Impurity Table 1.
Impurity Table 1
SPECIFIC TESTS
• Water Determination, Method I 921:
NMT 0.5%
• pH 791:
4.05.0. Use 50 mg/mL of the midodrine hydrochloride sample.
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers and store at room temperature.
• USP Reference Standards 11
USP Midodrine Hydrochloride RS
USP Midodrine Related Compound A RS
1-(2,5 Dimethoxyphenyl)-2-aminoethanol. C10H15NO3 197.23
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 3922
Pharmacopeial Forum: Volume No. 36(2) Page 414
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