Terazosin Tablets
DEFINITION
Terazosin Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of (C19H25N5O4·HCl), calculated as the free base.
IDENTIFICATION
• A. Ultraviolet Absorption 
197U
197U
Diluent:
0.1 N hydrochloric acid
Standard solution:
0.005 mg/mL of USP Terazosin Hydrochloride RS in Diluent. Sonicate for 10 min to completely dissolve. Pass the solution through a nylon filter of 0.45-µm pore size, discarding the first 5 mL of filtrate.
Sample solution:
Transfer 10 mg from the pool of ground Tablets (NLT 20) into a 100-mL flask. Dilute with Diluent to 50% of the volume of the flask. Sonicate the flask for 10 min. Allow it to cool to room temperature, and dilute with Diluent to volume. Further dilute 5 mL of this solution with Diluent to 100 mL, and mix well. Pass 20 mL of this preparation through a PTFE filter of 0.45-µm pore size, discarding the first 5 mL of filtrate.
• 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
[Note—Use an all-glass syringe. ]
Hydrochloric acid solution:
Prepare 0.01 N methanolic hydrochloric acid by adding 0.85 mL of hydrochloric acid to 1 L of methanol.
Diluent:
Hydrochloric acid solution and water (2:3)
Mobile phase:
Acetonitrile and water (7:3). Add 10.00 mL/L of glacial acetic acid, and degas. Pass through a nylon filter of 0.45-µm pore size. Pipet 0.20 mL of diethylamine into the solution, and mix.
Standard stock solution:
0.55 mg/mL of terazosin hydrochloride from USP Terazosin Hydrochloride RS in Diluent. Sonicate for 5 min to completely dissolve.
Standard solution:
0.055 mg/mL of terazosin hydrochloride in Diluent from the Standard stock solution. Pass through a PTFE filter of 0.45-µm pore size, discarding the first few mL of filtrate.
Naproxen standard solution:
0.5 mg/mL of USP Naproxen RS. Dissolve by sonication USP Naproxen RS in 25% of the volume of the flask of acetonitrile, and dilute with water to volume.
System suitability solution:
0.05 mg/mL of naproxen and 0.055 mg/mL of terazosin hydrochloride in Diluent from the Naproxen standard solution and Standard solution, respectively. Pass through a PTFE filter of 0.45-µm pore size, discarding the first few mL of filtrate.
Sample solution:
0.05 mg/mL of terazosin in Diluent. Combine the contents of NLT 20 Tablets, and weigh a quantity equivalent to 10 mg of terazosin into a 200-mL flask. Add 100 mL of Diluent, and sonicate for NLT 10 min. Shake the flask mechanically for NLT 10 min. Repeat until the sample is well dispersed. Allow the solution to cool, and dilute with Diluent to volume. Pass through a PTFE filter of 0.45-µm pore size, discarding the first few mL of filtrate.
Chromatographic system
Mode:
LC
Detector:
UV 254 nm
Column:
4.6-mm × 15-cm; 5-µm packing L1
Flow rate:
2.5 mL/min
Injection size:
25 µL
Run time:
NLT twice the retention time of the terazosin peak
System suitability
Samples:
Standard solution and System suitability solution
Suitability requirements
Resolution:
NLT 2.0 between naproxen and terazosin, System suitability solution
Tailing factor:
NMT 1.8 for the terazosin peak, System suitability solution
Relative standard deviation:
NMT 2.0, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C19H25N5O4, based on the label claim, in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response of terazosin from the Sample solution |
| rS | = | = peak response of terazosin from the Standard solution |
| CS | = | = concentration of terazosin hydrochloride in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of terazosin in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of terazosin, 387.43 |
| Mr2 | = | = molecular weight of terazosin hydrochloride, 423.89 |
Acceptance criteria:
90.0%–110.0%, calculated as the free base
PERFORMANCE TESTS
• Dissolution 711
711
Medium:
Water; 900 mL
Apparatus 2:
50 rpm
Time:
30 min
Standard solution:
6 µg/mL of USP Terazosin Hydrochloride RS in Medium.
Sample solution:
Pass a portion of the solution through a suitable filter of 0.45-µm pore size. Dilute with Medium to a concentration similar to that of the Standard solution, assuming complete dissolution of the label claim.
Spectrometric conditions
Mode:
UV
Analytical wavelength:
UV 245 nm
Cell length:
1 cm
Blank:
Medium
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C19H25N5O4 dissolved:
Result = (AU/AS) × (CS/L) × (Mr1/Mr2) × V × 100
| AU | = | = absorbance of the Sample solution |
| AS | = | = absorbance of the Standard solution |
| CS | = | = concentration of the Standard solution |
| L | = | = label claim (mg/Tablet) |
| Mr1 | = | = molecular weight of terazosin, 387.43 |
| Mr2 | = | = molecular weight of terazosin hydrochloride dihydrate, 459.92 |
| V | = | = volume of Medium (mL), 900 |
Tolerances:
NLT 75% (Q) of the labeled amount of terazosin (C19H25N5O4) is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Buffer:
Dissolve 4.1 g of monobasic potassium phosphate and 1.1 g of sodium 1-heptanesulfonate monohydrate in 950 mL of water. Adjust with phosphoric acid to a pH of 3.0 ± 0.10. Dilute with water to 1 L. Pass through a nylon filter of 0.45-µm pore size.
Mobile phase:
Acetonitrile and Buffer (6:19)
Standard solution:
0.003 mg/mL of terazosin hydrochloride from USP Terazosin Hydrochloride RS in Mobile phase
Sample solution:
Transfer 15 mg of the powder from the crushed Tablets (NLT 20) into a 50-mL volumetric flask. Dilute with Mobile phase to approximately half the volume of the flask. Sonicate for NLT 10 min, and shake the flask for NLT 20 min. Dilute with Mobile phase to volume, and pass through a nylon or Teflon filter of 0.45-µm pore size, discarding the first 5 mL of filtrate. The final concentration of the Sample solution is 0.3 mg/mL.
Sensitivity solution:
0.15 µg/mL of USP Terazosin Hydrochloride RS in Mobile phase from the Standard solution
Chromatographic system
Mode:
LC
Detector:
UV 246 nm
Column:
4.6-mm × 25-cm; 5-µm packing L1
Column temperature:
Ambient
Flow rate:
1 mL/min
Injection size:
10 µL
Run time:
NLT 1.2 times the retention time of terazosin in the Standard solution; NLT 4.5 times the retention time of terazosin in the Sample solution
System suitability
Samples:
Standard solution and Sensitivity solution
Capacity factor, k':
NLT 1.0 for the terazosin peak, Standard solution
Tailing factor:
NMT 2.0 for the terazosin peak, Standard solution
Relative standard deviation:
NMT 2.0%, Standard solution
Signal-to-noise ratio:
NLT 10 for the terazosin peak, Sensitivity solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (1/F) × (Mr1/Mr2) × 100
| rU | = | = peak response of each individual impurity from the Sample solution |
| rS | = | = peak response of terazosin from the Standard solution |
| CS | = | = concentration of terazosin hydrochloride in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of terazosin in the Sample solution (mg/mL) |
| F | = | = relative response factor (see Impurity Table 1) |
| Mr1 | = | = molecular weight of terazosin, 387.43 |
| Mr2 | = | = molecular weight of terazosin hydrochloride, 423.89 |
Acceptance criteria:
See Impurity Table 1.
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|
|---|---|---|---|---|
| Piperazinyl-ADMQa | 0.52 | 1.1 | 0.4 | |
| Chloro ADMQb | 1.37 | 1.2 | 0.4 | |
| Bis-ADMQ-piperazinec | 3.85 | 1.0 | 0.4 | |
| Any other individual, unspecified impurity | — | — | 0.2 | |
| Total impurities | — | — | 1.2 | |
|
a
N-(4-Amino-6,7 dimethoxy-2-quinazolinyl)piperazine.
b
2-Chloro-4-amino-6,7 dimethoxy-2-quinazoline.
c
N,N-Bis-(4-amino-6,7 dimethoxy-2-quinazolinyl)piperazine.
|
||||
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers protected from moisture and light. Store at controlled room temperature.
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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 4787
Pharmacopeial Forum: Volume No. 36(3) Page 687