Sertraline Tablets
711
Test 1(RB 1-Jun-2011)
Standard stock solution:
0.56 mg/mL of USP Sertraline Hydrochloride RS in Medium. A small volume of methanol, not exceeding 5% of the final volume, may be used to help solubilize sertraline.(RB 1-Jun-2011)
Test 2:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
• Labeling:
When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.(RB 1-Jun-2011)
DEFINITION
Sertraline Tablets contain an amount of sertraline hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of sertraline free base (C17H17Cl2N).
IDENTIFICATION
A.
The retention time of the major peak in the Sample solution corresponds to that in the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Mobile phase:
Methanol and 0.1% (v/v) phosphoric acid (1:1)
Standard solution:
0.05 mg/mL of USP Sertraline Hydrochloride RS in Mobile phase
Sample stock solution:
0.5 mg/mL prepared as follows. Transfer NLT 10 Tablets to a suitable volumetric flask. Dissolve in 0.1% phosphoric acid equivalent to 50% of the volume of the flask. Sonicate for 15 min with intermittent shaking to disperse the Tablets. Add an amount of methanol equivalent to 40% of the volume of the flask, and continue to sonicate for an additional 10 min. Cool the solution, and dilute with methanol to volume.
Sample solution:
0.05 mg/mL in Mobile phase from the Sample stock solution. Pass a portion of this solution through a nylon filter of 0.45-µm or finer pore size, discard the first few mL, and collect the rest of the filtrate.
Chromatographic system
Mode:
LC
Detector:
UV 210 nm
Column:
4.6-mm × 25-cm; 5-µm packing L10
Column temperature:
30
Flow rate:
1.5 mL/min
Injection size:
10 µL
Run time:
Twice the retention time of sertraline
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 1.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of sertraline (C17H17Cl2N) in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Sertraline Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of sertraline in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of sertraline, 306.23 |
| Mr2 | = | = molecular weight of sertraline hydrochloride, 342.69 |
Acceptance criteria:
90.0%–110.0% of sertraline free base
PERFORMANCE TESTS
Change to read:
• Dissolution 711
Test 1(RB 1-Jun-2011)
Medium:
Acetate buffer (3.0 g/L of sodium acetate trihydrate and 1.6 mL/L of glacial acetic acid. Adjust with glacial acetic acid to a pH of 4.5); 900 mL
Apparatus 2:
75 rpm
Time:
30 min
Standard stock solution:
0.56 mg/mL of USP Sertraline Hydrochloride RS in Medium. A small volume of methanol, not exceeding 5% of the final volume, may be used to help solubilize sertraline.(RB 1-Jun-2011)
Standard solution
For Tablets labeled to contain 50, 100, 150, or 200 mg:
0.056 mg/mL in Medium from the Standard stock solution
For Tablets labeled to contain 25 mg:
0.028 mg/mL in Medium from the Standard stock solution
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size. Dilute with Medium, if necessary.
Mobile phase:
Acetonitrile and 0.1% (v/v) phosphoric acid (1:3)
Chromatographic system
Mode:
LC
Detector:
UV 210 nm
Column:
4.6-mm × 25-cm; 5-µm packing L10
Column temperature:
40
Flow rate:
1.5 mL/min
Injection size:
10 µL for Tablets labeled to contain 50, 100, 150, or 200 mg; 20 µL for Tablets labeled to contain 25 mg
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
(RB 1-Jun-2011)
Samples:
Standard solution and Sample solution
Calculate the percentage of sertraline (C17H17Cl2N) dissolved:
Result = (rU/rS) × (CS/L) × (Mr1/Mr2) × D × V × 100
(RB 1-Jun-2011)| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Sertraline Hydrochloride RS in the Standard solution (mg/mL) |
| L | = | = label claim (mg/Tablet)(RB 1-Jun-2011) |
| Mr1 | = | = molecular weight of sertraline, 306.23 |
| Mr2 | = | = molecular weight of sertraline hydrochloride, 342.69 |
| D | = | = dilution factor for the Sample solution |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 80% (Q) of the labeled amount of sertraline (C17H17Cl2N) is dissolved.
Test 2:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium:
pH 4.5 acetate buffer (6.8 g/L of sodium acetate trihydrate and 32 mL/L of 2 N acetic acid. Adjust with 2 N acetic acid to a pH of 4.5); 900 mL
Apparatus 2:
75 rpm
Time:
45 min
Standard solution:
(L/800) mg/mL of USP Sertraline 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 0.45-µm pore size.
Buffer:
3 mL/L of glacial acetic acid and 7 mL/L of triethylamine in water
Mobile phase:
Acetonitrile, methanol, and Buffer (10:4:8)
Chromatographic system
Mode:
LC
Detector:
UV 273 nm
Column:
3.9-mm × 15-cm; 4-µm packing L1
Column temperature:
30
Flow rate:
1.0 mL/min
Injection size:
20 µL
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of sertraline (C17H17Cl2N) dissolved:
Result = (rU/rS) × (CS/L) × (Mr1/Mr2) × D × V × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Sertraline Hydrochloride RS in the Standard solution (mg/mL) |
| L | = | = label claim (mg/Tablet) |
| Mr1 | = | = molecular weight of sertraline, 306.23 |
| Mr2 | = | = molecular weight of sertraline hydrochloride, 342.69 |
| D | = | = dilution factor for the Sample solution |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 80% (Q) of the labeled amount of sertraline (C17H17Cl2N) is dissolved.(RB 1-Jun-2011)
(RB 1-Jun-2011)
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
• Organic Impurities
[Note—Use freshly prepared samples. ]
Buffer:
2.72 g/L of monobasic potassium phosphate. Adjust with triethylamine to a pH of 7.0.
Mobile phase:
Methanol, acetonitrile, and Buffer (6:3:11). Adjust with triethylamine to a pH of 8.0.
System suitability solution:
5 µg/mL of USP Sertraline Hydrochloride Racemic Mixture RS and 0.5 mg/mL of USP Sertraline Hydrochloride RS in Mobile phase
Standard solution:
2.5 µg/mL of USP Sertraline Hydrochloride RS in Mobile phase
Sample solution:
[Note—Sonicate for about 10 min with shaking to disperse the Tablets. ] Prepare a solution of 0.5 mg/mL of sertraline in Mobile phase from NLT 20 powdered Tablets. Pass a portion of this solution through a nylon filter of 0.45-µm or finer pore size, discard the first few mL, and use the filtrate.
Chromatographic system
Mode:
LC
Detector:
UV 210 nm
Column:
4.0-mm × 25-cm; 5-µm packing L45
Flow rate:
0.7 mL/min
Injection size:
20 µL
System suitability
Samples:
System suitability solution and Standard solution
[Note—The relative retention times for the 1R,4R cis-isomer of sertraline and of sertraline are 0.9 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 1.5 between sertraline and the 1R, 4R cis-isomer of sertraline hydrochloride, System suitability solution
Relative standard deviation:
NMT 5%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each individual impurity (other than process related) in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response of each individual impurity from the Sample solution |
| rS | = | = peak response of sertraline from the Standard solution |
| CS | = | = concentration of USP Sertraline Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of sertraline in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of sertraline, 306.23 |
| Mr2 | = | = molecular weight of sertraline hydrochloride, 342.69 |
Acceptance criteria
[Note—Disregard any peak below 0.1%. ]
Individual impurities:
NMT 0.2% of any individual impurity
Total impurities:
NMT 2.0%
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers, and store at controlled room temperature.
Add the following:
• Labeling:
When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.(RB 1-Jun-2011)
• USP Reference Standards 11
11
USP Sertraline Hydrochloride RS 
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USP Sertraline Hydrochloride Racemic Mixture RS
(1RS,4RS)-4-(3,4-Dichlorophenyl)-N-methyl-1,2,3,4-tetrahydro-1-naphthylamine hydrochloride.
C17H17Cl2N·HCl 342.69
(1RS,4RS)-4-(3,4-Dichlorophenyl)-N-methyl-1,2,3,4-tetrahydro-1-naphthylamine hydrochloride.
C17H17Cl2N·HCl 342.69
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Hariram Ramanathan, M.S.
Associate Scientific Liaison 1-301-816-8313 |
(SM42010) Monographs - Small Molecules 4 |
| 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 4630
Pharmacopeial Forum: Volume No. 36(1) Page 138