Printed on: Fri Feb 02 2024, 02:14:05 AM(EST) Status: Currently Official on 02-Feb-2024 DocId: GUID-58D54B12-BB2B-4732-AB76-11BF8A765BDC_4_en-US

Printed by: Budi Prasaja Official Date: Official as of 01-May-2020 Document Type: USP @2024 USPC
Do Not Distribute DOI Ref: ojp41 DOI: https://doi.org/10.31003/USPNF_M1053_04_01
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Flow rate: 1.0 mL/min

Tadalafil Tablets
DEFINITION
Tadalafil Tablets contain NLT 90.0% and NMT 110.0% of the
labeled amount of tadalafil (C22H19N3O4).
IDENTIFICATION
Change to read:
• A. ▲SPECTROSCOPIC IDENTIFICATION TESTS á197ñ, Infrared
Spectroscopy 197D or 197K▲ (CN 1-May-2020)
Standard: Add 10 mg of USP Tadalafil RS to 15 mL of water.
Shake for 20 min, centrifuge for 10 min, and discard the
supernatant. Suspend the precipitate in 8 mL of ethyl
acetate, and shake for 5 min. Centrifuge for 10 min, and
collect the supernatant. Dry the supernatant under a stream
of nitrogen. The supernatant may be heated up to 70° to
aid evaporation of the ethyl acetate. [NOTE—Ethyl acetate
must be completely removed to prevent interference in the
spectrum.]
Sample: Transfer a quantity of Tablets, equivalent to 10–
20 mg of tadalafil, into a suitable container. Add 15 mL of
Injection volume: 10 µL
System suitability
Samples: Standard solution and System suitability solution
[NOTE—The relative retention times for tadalafil and
the 6R,12aS diastereomer of tadalafil are about
1.0 and 1.2, respectively.]
Suitability requirements
Resolution: NLT 3 between tadalafil and the 6R,12aS
diastereomer peak, System suitability solution
Tailing factor: NMT 1.5, Standard solution
Relative standard deviation: NMT 2.0%, Standard
solution
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of tadalafil
(C22H19N3O4) 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

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water, and shake for 10 min, or until the Tablets are CS = concentration of USP Tadalafil RS in the Standard
completely dispersed. Centrifuge for 10 min, and discard solution (mg/mL)
the supernatant. Suspend the precipitate in 8 mL of ethyl CU = nominal concentration of tadalafil in the Sample
acetate, and shake for 5 min. Centrifuge for 10 min, and solution (mg/mL)
collect the supernatant. Dry the supernatant under a stream
Acceptance criteria: 90.0%–110.0%
of nitrogen. The supernatant may be heated up to 70° to
aid evaporation of the ethyl acetate. [NOTE—Ethyl acetate
must be completely removed to prevent interference in the
spectrum.]
ci PERFORMANCE TESTS
• DISSOLUTION á711ñ
Test 1
Acceptance criteria: Meet the requirements over the range Medium: 0.5% sodium dodecyl sulfate; 1000 mL
ffi
from 1700–400 cm−1 Apparatus 2: 50 rpm, use suitable sinkers if necessary
• B. The retention time of the major peak of the Sample Times: 10 and 30 min
solution corresponds to that of the Standard solution, as Mobile phase: Methanol and water (50:50)
obtained in the Assay. Standard stock solution: 0.25 mg/mL of USP Tadalafil RS
in acetonitrile and water (1:1)
ASSAY
Standard solution: 0.0075 mg/mL of USP Tadalafil RS in
• PROCEDURE
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Medium from the Standard stock solution

Mobile phase: Acetonitrile, water, and trifluoroacetic acid
Sample solution: Pass a portion of the solution under test
(35:65: 0.1)
through a suitable filter.
Diluent: Acetonitrile and water (1:1)
Chromatographic system
Standard solution: 0.25 mg/mL of USP Tadalafil RS in
(See Chromatography á621ñ, System Suitability.)
Diluent
Mode: LC
System suitability solution: To partially convert tadalafil
Detector: UV 225 nm
to the 6R,12aS diastereomer, transfer 25 mL of the Standard
Column: 4.6-mm × 5.0-cm; 3.5-µm packing L7
solution into a suitable container. Add 0.25 mL of 5 N
Column temperature: 40°
sodium hydroxide, mix well, and let stand for 30 min.
Flow rate: 2.0 mL/min
Neutralize the solution to pH 7 by drop-wise addition of
Injection volume: 50 µL
trifluoroacetic acid. [NOTE—This solution is stable for 1
System suitability
month when stored in a refrigerator.]
Sample: Standard solution
Sample solution: Place NLT 20 Tablets into an appropriate
Suitability requirements
size volumetric flask. Fill the flask about halfway with
Tailing factor: NMT 1.5
Diluent, and shake the mixture for about 15 min to
Relative standard deviation: NMT 2.0%
disintegrate the Tablets. If any large fragments remain,
Analysis
sonicate the solution for 2 min or until fragments are
Samples: Standard solution and Sample solution
dispersed. Dilute with Diluent to volume, and mix. Allow
Calculate the percentage of the labeled amount of
the solution to stand for at least 1 h to further aid Tablet
tadalafil (C22H19N3O4) dissolved at each time point (Qi):
dissolution. If necessary, shake the solution and perform a
secondary dilution to obtain a final nominal concentration
Q10 = (rU/rS) × (CS/L) × V × 100
of 0.25 mg/mL. Centrifuge or filter the solution. [NOTE—The
initial concentration before a secondary dilution step Q30 = (Q10 × v/V) + [(rU/rS) × (CS/L) × (V − v) × 100]
should not exceed 6 mg/mL.]
Chromatographic system rU = peak response from the Sample solution
(See Chromatography á621ñ, System Suitability.) rS = peak response from the Standard solution
Mode: LC CS = concentration of USP Tadalafil RS in the Standard
Detector: UV 285 nm solution (mg/mL)
Column: 4.6-mm × 15-cm; 3.5-µm packing L7 L = label claim (mg/Tablet)
Column temperature: 35° V = volume of Medium, 1000 mL

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Printed on: Fri Feb 02 2024, 02:14:05 AM(EST) Status: Currently Official on 02-Feb-2024 DocId: GUID-58D54B12-BB2B-4732-AB76-11BF8A765BDC_4_en-US
Printed by: Budi Prasaja Official Date: Official as of 01-May-2020 Document Type: USP @2024 USPC
Do Not Distribute DOI Ref: ojp41 DOI: https://doi.org/10.31003/USPNF_M1053_04_01
2

v = volume of the sample withdrawn at initial time AS = absorbance of the Standard solution
point (mL) CS = concentration of USP Tadalafil RS in the Standard
solution (mg/mL)
Tolerances: NLT 40% (Q) of the labeled amount of CU = nominal concentration of tadalafil in the Sample
tadalafil is dissolved in 10 min and NLT 80% (Q) of the solution (mg/mL)
labeled amount of tadalafil is dissolved in 30 min.
Test 2: If the product complies with this procedure, the Acceptance criteria: Meet the requirements for coated
labeling indicates that it meets USP Dissolution Test 2. Tablets
Medium, Mobile phase, Standard stock solution,
Standard solution, Sample solution, and IMPURITIES
Chromatographic system: Proceed as directed in Test 1. • ORGANIC IMPURITIES
Apparatus 2: 50 rpm, use suitable sinkers if necessary Mobile phase, Diluent, Standard solution, System
Time: 15 min suitability solution, Sample solution, and
Analysis Chromatographic system: Proceed as directed in the
Samples: Standard solution and Sample solution Assay.
Calculate the percentage of the labeled amount of Sensitivity solution: 0.25 µg/mL of USP Tadalafil RS in
tadalafil (C22H19N3O4) dissolved: Diluent from the Standard solution
System suitability
Result = (rU/rS) × CS × V × (1/L) × 100 Samples: Standard solution, System suitability solution, and
Sensitivity solution
rU = peak response of tadalafil from the Sample [NOTE—The relative retention times for tadalafil and
solution the 6R,12aS diastereomer of tadalafil are about
rS = peak response of tadalafil from the Standard 1.0 and 1.2, respectively.]

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solution Suitability requirements
CS = concentration of USP Tadalafil RS in the Standard Tailing factor: NMT 1.5, Standard solution
solution (mg/mL) Relative standard deviation: NMT 2.0%, Standard
V = volume of Medium, 1000 mL solution
L = label claim (mg/Tablet)
ci Resolution: NLT 3 between tadalafil and the 6R,12aS
diastereomer peak, System suitability solution
Tolerances: NLT 80% (Q) of the labeled amount of Signal-to-noise ratio: NLT 20, Sensitivity solution
tadalafil (C22H19N3O4) is dissolved. Analysis
• UNIFORMITY OF DOSAGE UNITS á905ñ Sample: Sample solution
Procedure for content uniformity Calculate the percentage of each impurity in the portion of
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Diluent: Acetonitrile and water (1:1) Tablets taken:
Standard solution: 0.1–0.2 mg/mL of USP Tadalafil RS in
Diluent Result = (rU/rT) × 100
Sample solution: Add 1 Tablet to a suitable volumetric
flask to prepare a solution having a nominal concentration rU = peak response of each impurity from the Sample
of 0.1–0.2 mg/mL of tadalafil. Add a volume of Diluent solution
rT = sum of the peak responses from the Sample
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equivalent to 50% of the volume of the flask, and

mechanically shake for 15 min. Dilute with Diluent to solution
volume, and pass a portion of the solution through a
Acceptance criteria
suitable filter of 0.45-µm pore size, discarding the first 2–
Individual impurities: NMT 0.2%
3 mL.
Total impurities: NMT 0.3%
Instrumental conditions
Reporting level for impurities: 0.05%
(See Ultraviolet-Visible Spectroscopy á857ñ.)
Mode: UV ADDITIONAL REQUIREMENTS
Cell: 0.1 cm • PACKAGING AND STORAGE: Preserve in tight containers.
Analytical wavelength: Absorption maximum at about Store at controlled room temperature.
285 nm • LABELING: When more than one Dissolution test is given, the
Analysis labeling states the Dissolution test used only if Test 1 is
Samples: Standard solution and Sample solution not used.
Calculate the percentage of the labeled amount of • USP REFERENCE STANDARDS á11ñ
tadalafil (C22H19N3O4) in the Tablet taken: USP Tadalafil RS
Result = (AU/AS) × (CS/CU) × 100

AU = absorbance of the Sample solution

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