Terazosin Capsules
DEFINITION
Terazosin Capsules 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
Diluent:  0.1 N hydrochloric acid
Standard solution:  0.005 mg/mL of terazosin hydrochloride from 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.
Sample solution:  Combine the contents from 20 Capsules and transfer 10 mg into a 100-mL flask. Fill with Diluent to 50% of the volume of the flask. Sonicate the flask for 10 min. Allow it to cool to room temperature. Dilute with Diluent to volume. Further dilute 5 mL of this solution with Diluent to 100 mL, and mix well. Pass 10 mL of this preparation through a PTFE filter with a 0.45-µm pore size.
Blank:  Pass the Diluent through a PTFE filter of 0.45-µm pore size.
•  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 0.1 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). Pass through a nylon filter of 0.45-µm pore size. Add 10 mL/L of glacial acetic acid, and degas. After degassing, 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 Standard stock solution. Pass through a PTFE filter of 0.45-µm pore size, discarding NLT the first 8 mL of filtrate.
Sample solution:  Combine the contents of NLT 20 Capsules 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 8 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 
Sample:  Standard solution
Suitability requirements 
Tailing factor:  NMT 1.8 for the terazosin peak
Relative standard deviation:  NMT 2.0%
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of terazosin (C19H25N5O4), based on the label claim, in the portion of Capsules 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
Test 1 
Medium:  Water; 900 mL
Apparatus 2:  50 rpm, with sinkers
Time:  60 min
Standard solution:  (387.44/423.89)(L/900) mg/mL of USP Terazosin Hydrochloride RS in Medium, where L is the Capsule label claim (terazosin), in mg
Sample solution:  At the designated time, withdraw 20 mL of the solution under test, and centrifuge at NMT 3000 rpm for 20 min.
Capsule blank solution:  Dissolve 10 empty Capsule shells in 900 mL of Medium heated to 37. Centrifuge a portion of this solution for 20 min.
Spectrometric conditions 
Mode: 
UV
Analytical wavelength:  UV 245 nm
Cell length:  5 cm for Capsules labeled to contain 1 mg; 1 cm for Capsules labeled to contain 2 or 5 mg; 0.2 cm for Capsules labeled to contain 10 mg
Blank:  Medium
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of terazosin dissolved:
Result = {[AU (AB/10)]/AS} × CS/L × V × 100
AU== absorbance of the Sample solution
AB== absorbance of the Capsule blank solution
AS== absorbance of the Standard solution
CS== concentration of terazosin in the Standard solution (mg/mL)
L== terazosin label claim (mg/Capsule)
V== volume of Medium, 900 mL
Tolerances:  NLT 80% (Q) of the labeled amount of terazosin is dissolved.
Test 2:  If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2.
Medium:  Water; 900 mL
Apparatus 2:  50 rpm, with wire helix sinker.
Time:  30 min
0.1 M phosphate buffer:  13.6 g/mL of monobasic potassium phosphate and 4 mL/L of triethylamine in water. Adjust with phosphoric acid to a pH of 2.5 ± 0.05.
Mobile phase:  Acetonitrile and 0.1 M phosphate buffer (1:3)
Standard solution:  (387.44/423.89)(L/900) mg/mL of USP Terazosin Hydrochloride RS in Medium, where L is the Capsule label claim (terazosin), in mg
Sample solution:  Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.
Chromatographic system 
Mode:  LC
Detector:  UV 246 nm
Column:  3.9-mm × 30-cm; 10-µm packing L11
Flow rate:  1.0 mL/min
Injection size:  50 µL
System suitability 
Sample:  Standard solution
Suitability requirements 
Relative standard deviation:  NMT 2.0%
Analysis 
Samples:   Standard solution and Sample solution
Calculate the percentage of terazosin dissolved:
Result = (rU/rS) × (CS/L) × V × 100
rU== peak response from the Sample solution
rS== peak response from the Standard solution
CS== concentration of terazosin in the Standard solution (mg/mL)
L== terazosin label claim (mg/Capsule)
V== volume of Medium, 900 mL
Tolerances:  NLT 80% (Q) of the labeled amount of terazosin is dissolved.
•  Uniformity of Dosage Units 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 terazosin from the contents of 20 Capsules 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
Flow rate:  1 mL/min
Injection size:  10 µL
Run time:  NLT 1.2 times the retention time of terazosin for the Standard solution and Sensitivity 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 Capsules 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.
•  Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.
•  USP Reference Standards 11
USP Terazosin Hydrochloride RS Click to View Structure
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
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Senior Scientific Liaison
1-301-816-8349
(SM22010) Monographs - Small Molecules 2
711 Margareth R.C. Marques, Ph.D.
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1-301-816-8106
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USP35–NF30 Page 4783
Pharmacopeial Forum: Volume No. 36(3) Page 685