Midodrine Hydrochloride Tablets
DEFINITION
Midodrine Hydrochloride Tablets contain NLT 90.0% and NMT 105.0% of the labeled amount of Midodrine Hydrochloride (C12H18N2O4·HCl).
IDENTIFICATION
• A. Infrared Absorption 
197K
197K
Sample specimen:
Weigh a quantity, from finely powdered Tablets (NLT 20), equivalent to 15 mg of midodrine hydrochloride, into a 50-mL disposable centrifuge tube. Add 20 mL of water, and stir for 2 min using a vortex mixer. Pass the mixture through filter paper into a 50-mL beaker, and boil it until about 2 mL of the solution is left. Evaporate the final solution in an oven at 105
for 1 h.
for 1 h.
• B.
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
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 from NLT 5 Tablets (for 10-mg Tablet strength) or NLT 10 Tablets (for 5-mg and 2.5-mg Tablet strength). Initially add Mobile phase up to 80% of the volume of the flask. Sonicate for 10 min, stir for 15 min, and then dilute to volume, mix, and let stand for 10 min. Pass through a suitable PVDF filter of 0.45-µm pore size, and discard the first 5 mL.
Chromatographic system
Mode:
LC
Detector:
UV 290 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Flow rate:
1.0 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 the labeled amount of midodrine hydrochloride (C12H18N2O4·HCl) in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| CU | = | = nominal concentration of the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–105.0%
PERFORMANCE TESTS
• Dissolution 711
711
Medium:
0.1 N HCl; 900 mL, deaerated
Apparatus 2:
50 rpm
Time:
15 min
Buffer:
Proceed as directed in the Assay.
Mobile phase:
Acetonitrile and Buffer (3:17)
Standard solution:
L/900 mg/mL of USP Midodrine Hydrochloride RS in Medium, where L is the label claim in mg/Tablet
Sample solution:
Pass a portion of the solution under test through a suitable filter of 45-µm pore size.
Chromatographic system
Mode:
LC
Detector:
UV 290 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Flow rate:
1.0 mL/min
Injection size:
50 µL
System suitability
Sample:
Standard solution
Suitability requirements
Column efficiency:
NLT 2000 theoretical plates
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of midodrine hydrochloride dissolved:
Result = (rU/rS) × (CS/L) × V × 100
| rU | = | = peak area from the Sample solution |
| rS | = | = peak area from the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| L | = | = label claim (mg/Tablet) |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 80% (Q) of the labeled amount of midodrine hydrochloride is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Buffer and Mobile phase:
Proceed as directed in the Assay.
Standard stock solution 1:
25 µg/mL of USP Midodrine Hydrochloride RS in Mobile phase
Standard stock solution 2:
25 µg/mL of USP Midodrine Related Compound A RS in Mobile phase
Standard solution:
1.25 µg/mL each of USP Midodrine Hydrochloride RS and USP Midodrine Related Compound A RS in Mobile phase from Standard stock solution 1 and Standard stock solution 2
Sample solution:
0.25 mg/mL in Mobile phase from NLT 5 Tablets (for 10-mg Tablet strength) and NLT 10 Tablets (for 5-mg and 2.5-mg Tablet strength). Initially add Mobile phase to about 80% of the volume of the flask. Sonicate for 10 min, stir for 15 min, and then dilute to volume. Pass through a suitable PVDF filter of 0.45-µm pore size, and discard the first 5 mL.
Chromatographic system
Proceed as directed in the Assay except for the following:
Injection volume:
40 µL
System suitability
Sample:
Standard solution
Suitability requirements
[Note—The relative retention times for midodrine related compound A and midrodrine hydrochloride are 0.83 and 1, respectively. ]
Resolution:
NLT 2.0 between midodrine hydrochloride and midodrine related compound A
Column efficiency:
NLT 2000 theoretical plates for the midodrine peak
Tailing factor:
NMT 2.0 for the midodrine peak
Relative standard deviation:
NMT 2.0% for the midodrine peak
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of midodrine related compound A in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of midodrine related compound A from the Sample solution |
| rS | = | = peak response of midodrine related compound A from the Standard solution |
| CS | = | = concentration of USP Midodrine Related Compound A RS in the Standard solution (µg/mL) |
| CU | = | = nominal concentration of midodrine hydrochloride in the Sample solution (µg/mL) |
Calculate the percentage of any other unknown impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of any other unknown impurity from the Sample solution |
| rS | = | = peak response of midodrine from the Standard solution |
| CS | = | = concentration of USP Midodrine Hydrochloride RS in the Standard solution (µg/mL) |
| CU | = | = nominal concentration of midodrine hydrochloride in the Sample solution (µg/mL) |
Acceptance criteria
Individual impurities:
NMT 0.5% of midodrine related compound A; NMT 0.2% of any other individual impurity
Total impurities:
NMT 1.0%
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers.
• USP Reference Standards 11
11
USP Midodrine Hydrochloride RS
USP Midodrine Related Compound A RS
1-(2,5 Dimethoxyphenyl)-2-aminoethanol.
C10H15NO3 197.23
1-(2,5 Dimethoxyphenyl)-2-aminoethanol.
C10H15NO3 197.23
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Sujatha Ramakrishna, Ph.D.
Senior Scientific Liaison 1-301-816-8349 |
(SM22010) Monographs - Small Molecules 2 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3923
Pharmacopeial Forum: Volume No. 36(2) Page 415