Sertraline Hydrochloride Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION 

Sertraline Hydrochloride 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). 

2 IDENTIFICATION 

A, The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. 

3 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 of sertraline free base prepared as follows. Transfer NLT 10 Tablets to a suitable volumetric flask. Dissolve in 0.1% phosphoric acid equivalent to 50% of the flask volume. Sonicate for 15 min with intermittent shaking to disperse the Tablets. Add an amount of methanol equivalent to 40% of the flask volume, and continue to sonicate for an additional 10 min. Cool the solution, and dilute with methanol to volume. 

Sample solution: Nominally 0.05 mg/mL of sertraline free base 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 

(See Chromatography 〈621〉, System Suitability.) 

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 volume: 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 the labeled amount of sertraline free base (C₁₇H₁₇Cl₂N) in the portion of Tablets taken: 

Result = (r_U/r_S) × (C_S/C_U) × (M_r1 /M_r2) × 100 

r_U = peak response from the Sample solution 

r_S = peak response from the Standard solution  

C_S = concentration of USP Sertraline Hydrochloride RS in the Standard solution (mg/mL)  

C_U = nominal concentration of sertraline in the Sample solution (mg/mL) 

M_r1 = molecular weight of sertraline  306.23  

M_r2 = molecular weight of sertraline hydrochloride, 342.69

Acceptance criteria: 90.0%–110.0% of sertraline free base 

4 PERFORMANCE TESTS 

Dissolution 〈711〉 

Test 1 

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 nal volume, may be used to help solubilize sertraline. 

Standard solution 

For Tablets labeled to contain 50, 100, 150, or 200 mg: 0.056 mg/mL of USP Sertraline Hydrochloride RS in Medium from the Standard stock solution 

For Tablets labeled to contain 25 mg: 0.028 mg/mL of USP Sertraline Hydrochloride RS 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 

(See Chromatography 〈621〉, System Suitability.) 

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 volume 

For Tablets labeled to contain 50, 100, 150, or 200 mg: 10 µL 

For Tablets labeled to contain 25 mg: 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 the labeled amount of sertraline free base (C₁₇H₁₇Cl₂N) dissolved: 

Result = (r_U/r_S) × (C_S/L) × (M_r1 /M_r2) × D x V x 100 

r_U = peak response from the Sample solution 

r_S = peak response from the Standard solution  

C_S = concentration of USP Sertraline Hydrochloride RS in the Standard solution (mg/mL)  

M_r1 = molecular weight of sertraline  306.23  

M_r2 = molecular weight of sertraline hydrochloride, 342.69

L = label claim (mg/Tablet) 

D = dilution factor for the Sample solution 

V = volume of Medium, 900 mL 

Tolerances: NLT 80% (Q) of the labeled amount of sertraline free base (C₁₇H₁₇Cl₂N) is dissolved. 

Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2. www.webofpharma.com

2/16/25, 5:14 PM USP-NF Sertraline Hydrochloride Tablets 

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 

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) 

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. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

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 volume: 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 the labeled amount of sertraline free base (C₁₇H₁₇Cl₂N) dissolved: 

Result = (r_U/r_S) × (C_S/L) × (M_r1 /M_r2) × D x V x 100 

r_U = peak response from the Sample solution 

r_S = peak response from the Standard solution  

C_S = concentration of USP Sertraline Hydrochloride RS in the Standard solution (mg/mL)  

L = label claim (mg/Tablet)

M_r1 = molecular weight of sertraline  306.23  

M_r2 = 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 free base (C₁₇H₁₇Cl₂N) is dissolved. 

Test 3: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3. 

Medium: pH 4.5 acetate buffer (6.8 g/L of sodium acetate trihydrate; adjust with 2 N acetic acid to a pH of 4.5); 900 mL Apparatus 2: 75 rpm 

Time: 30 min 

Buffer: Dissolve 0.8 g/L of ammonium acetate in water and add 10 mL of triethylamine. Adjust with phosphoric acid to a pH of 5.0 ± 0.05. Mobile phase: Acetonitrile and Buffer (35:65) 

Standard stock solution: 0.6 mg/mL of USP Sertraline Hydrochloride RS in Medium, prepared as follows. Place an appropriate amount of USP Sertraline Hydrochloride RS into a suitable volumetric flask and add 70% of the nal flask volume of Medium. Sonicate to dissolve and dilute with Medium to volume. Pass through a suitable filter of 0.45-µm pore size. 

Standard solution: (L/800) mg/mL of USP Sertraline Hydrochloride RS in Medium from Standard stock solution, 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. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 220 nm 

Column: 4.6-mm × 15-cm; 5-µm packing L1 

Column temperature: 50° 

Flow rate: 2.0 mL/min 

Injection volume: 20 µL 

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 the labeled amount of sertraline free base (C₁₇H₁₇Cl₂N) dissolved: 

Result = (r_U/r_S) × (C_S/L) × (M_r1 /M_r2) x V x 100 

r_U = peak response from the Sample solution 

r_S = peak response from the Standard solution  

C_S = concentration of USP Sertraline Hydrochloride RS in the Standard solution (mg/mL)  

L = label claim (mg/Tablet)

M_r1 = molecular weight of sertraline  306.23  

M_r2 = molecular weight of sertraline hydrochloride, 342.69

V = volume of Medium, 900 mL 

Tolerances: NLT 80% (Q) of the labeled amount of sertraline free base (C₁₇H₁₇Cl₂N) is dissolved. 

Uniformity of Dosage Units 〈905〉: Meet the requirements 

5 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 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 210 nm 

Column: 4.0-mm × 25-cm; 5-µm packing L45 

Flow rate: 0.7 mL/min 

Injection volume: 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 sertraline are 0.9 and 1.0, respectively.] Suitability requirements 

Resolution: NLT 1.5 between sertraline and the 1R,4R-cis-isomer of sertraline, System suitability solution 

Relative standard deviation: NMT 5%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of each individual degradation product in the portion of Tablets taken: 

Result = (r_U/r_S) × (C_S/C_U) × (M_r1 /M_r2) × 100 

r_U = peak response of each individual degradation product from the Sample solution

r_S = peak response of sertraline from the Standard solution  

C_S = concentration of USP Sertraline Hydrochloride RS in the Standard solution (mg/mL)  

C_U = nominal concentration of sertraline in the Sample solution (mg/mL) 

M_r1 = molecular weight of sertraline, 306.23  

M_r2 = molecular weight of sertraline hydrochloride, 342.69 

Acceptance criteria 

Disregard any peak below 0.1%. Disregard the peak due to the process impurity 1R,4R-cis-isomer of sertraline. Individual degradation product: NMT 0.2% 

Total degradation products: NMT 2.0%, excluding the 1R,4R-cis-isomer of sertraline 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in well-closed containers, and 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 Sertraline Hydrochloride RS 

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