Sertraline Hydrochloride

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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C₁₇H₁₇Cl₂N. HCl 342.69 

1-Naphthalenamine, 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-, hydrochloride, (1S-cis)-; 

(1S,4S)-4-(3,4-Dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthylamine hydrochloride CAS RN®: 79559-97-0; UNII: UTI8907Y6X. 

1 DEFINITION 

Sertraline Hydrochloride contains NLT 97.0% and NMT 102.0% of sertraline hydrochloride (C₁₇H₁₇Cl₂N. HCl), calculated on the anhydrous basis.  

2 IDENTIFICATION 

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M 

B. The retention time of the major peak of the Sample solution corresponds to that of sertraline hydrochloride from the System suitability solution, as obtained in the test for Limit of (R,R) Sertraline Hydrochloride. 

Change to read: 

C. Identification Tests—General 〈191〉, Chemical Identification Tests, Chloride 

Sample solution: 1 mg/mL of Sertraline Hydrochloride in a mixture of dehydrated alcohol and water(50:50),  prepared as follows. Dissolve 10 mg of Sertraline Hydrochloride in 5 mL of dehydrated alcohol. Add 5 mL of water to the solution. Acceptance criteria: Meets the requirements   

3 ASSAY 

Change to read: 

Procedure 

Buffer: To 28.6 mL of glacial acetic acid, slowly add, while stirring, 34.8 mL of triethylamine, and dilute with water to 100 mL. Dilute 10 mL of the resulting solution with water to 1 L. 

Mobile phase: Acetonitrile, methanol, and Buffer (45:15:40) 

Standard solution: 0.05 mg/mL of USP Sertraline Hydrochloride RS in Mobile phase 

Sample solution: 0.05 mg/mL of Sertraline Hydrochloride in Mobile phase 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 3.9-mm × 15-cm; 4-µm packing L1 

Column temperature: 30° 

Flow rate: 1.8 mL/min 

Injection volume: 20 µL 

Run time: NLT  2 times the retention time of sertraline 

System suitability 

Sample: Standard solution 

Suitability requirements 

Tailing factor: NMT 2.0 

Relative standard deviation: NMT 0.73%  

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of sertraline hydrochloride (C₁₇H₁₇Cl₂N.HCl) in the portion of Sertraline Hydrochloride taken:  

Result = (r_U/r_S) × (C_S/C_U) × 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 = concentration of Sertraline Hydrochloride in the Sample solution (mg/mL) 

Acceptance criteria: 97.0%–102.0% on the anhydrous basis 

4 IMPURITIES 

Residue on Ignition 〈281〉: NMT 0.3% 

Change to read: 

Limit of (R,R) Sertraline Hydrochloride 

Solution A: Transfer 10.0 mL of ammonium hydroxide to a 100-mL volumetric flask. Dilute with water to volume.  Mobile phase: Chromatographic solvent hexane,  2-propanol, and diethylamine(96:  4:  0.15)  

System suitability solution: Transfer 10 mg of USP Sertraline Hydrochloride Racemic Mixture RS into a 20-mL volumetric flask. Add 4 mL of Solution A  and 10 mL of chromatographic solvent hexane.  Shake well until the organic phase is clear. Wait for phase separation, transfer about 2.0 mL from the top layer into a 20-mL volumetric flask, and dilute with chromatographic solvent hexane  to volume. 

Standard solution: Transfer 10 mg of USP Sertraline Hydrochloride RS into a 20-mL volumetric flask. Add 4 mL of Solution A (USP 1-May 2021) and 10 mL of chromatographic solvent hexane.  Shake well until the organic phase is clear. Wait for phase separation, transfer 1.0 mL from the top layer into a 10-mL volumetric flask, and dilute with chromatographic solvent hexane (USP 1-May 2021) to volume. Further dilute quantitatively and stepwise, if necessary, to obtain a solution having a known concentration of 0.01 mg/mL. 

Sample solution: Transfer 20 mg of Sertraline Hydrochloride to a 20-mL volumetric flask. Add 4 mL of Solution A  and 10 mL of chromatographic solvent hexane.  Shake well until the organic phase is clear. Wait for phase separation, and use the top layer. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 235 nm 

Column: 4.6-mm × 25-cm; 5-µm packing L40 

Column temperature: 5° 

Flow rate: 1 mL/min 

Injection volume: 20 µL 

Run time: NLT 4.5 times the retention time of sertraline  

System suitability 

Sample: System suitability solution 

[Note—The relative retention times for sertraline and (R,R) sertraline are about 1.0 and 1.16, respectively.] 

Suitability requirements 

Resolution: NLT 2.8 between sertraline and (R,R) sertraline 

Relative standard deviation: NMT 10.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of (R,R) sertraline hydrochloride in the portion of Sertraline Hydrochloride taken: 

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response of (R,R) sertraline 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 = concentration of Sertraline Hydrochloride in the Sample solution (mg/mL) 

Acceptance criteria: NMT 1.5% 

Change to read: 

Organic Impurities, Procedure 1 

Depending on the synthetic route, perform Organic Impurities, Procedure 2 and Limit of Mandelic Acid; or perform Organic Impurities, Procedure 1.  If sertralone is a known process impurity, then the tests for Organic Impurities, Procedure 2, and Limit of Mandelic Acid are recommended. 

Buffer: 5.8 g/L of monobasic ammonium phosphate in water. Adjust with phosphoric acid to a pH of 4.2. 

Mobile phase: Methanol and Buffer (48:52) 

System suitability solution: 0.5 mg/mL each of USP Sertraline Hydrochloride RS and USP Sertraline Hydrochloride Related Compound A RS in Mobile phase 

Standard solution: 0.5 µg/mL of USP Sertraline Hydrochloride RS in Mobile phase 

Sample solution: 0.5 mg/mL of Sertraline Hydrochloride in Mobile phase 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 220 nm 

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

Column temperature: 30° 

Flow rate: 1 mL/min 

Injection volume: 20 µL 

Run time: NLT 3 times the retention time of sertraline  

System suitability 

Samples: System suitability solution and Standard solution 

[Note—See Table 1 for the relative retention times.] 

Suitability requirements 

Resolution: NLT 2.2 between sertraline hydrochloride related compound A (trans-R,S isomer) and sertraline, System suitability solution Relative standard deviation: NMT 10.0%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of each individual impurity in sertraline hydrochloride (C₁₇H₁₇Cl₂N. HCl) in the portion of Sertraline  Hydrochloride taken: 

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response of each individual impurity 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 = concentration of Sertraline Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: See Table 1. The reporting threshold is 0.05%.  

Table 1 

a (1RS,4RS)-4-(2,3-Dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine.

b (1RS,4RS)-4-(3-Chlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine. 

c (1RS,4RS)-4-(4-Chlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine.   

Change to read: 

Organic Impurities, Procedure 2 

Solution A: 250 g/L of anhydrous potassium carbonate in water  

System suitability solution: Dissolve 50 mg of USP Sertraline Hydrochloride RS and 0.5 mg of USP Sertraline Hydrochloride Related Compound A RS in 2 mL of methanol in a stoppered centrifuge tube. Add 0.2 mL of Solution A,  and mix in a vortex mixer for 30 s. Add 8 mL of methylene chloride. Stopper the tube, and mix in a vortex mixer for 60 s. Add 1 g of anhydrous sodium sulfate. Mix well, and centrifuge for 5 min. 

Sample solution: Dissolve 250 mg of Sertraline Hydrochloride in 2 mL of methanol in a stoppered centrifuge tube. Add 0.2 mL of Solution A,  and mix in a vortex mixer for 30 s. Add 8 mL of methylene chloride. Stopper the tube, and mix in a vortex mixer for 60 s. Add 1 g of anhydrous sodium sulfate. Mix well, and centrifuge for 5 min. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: GC 

Detector: Flame-ionization 

Column: 30-m × 0.53-mm fused silica column coated with a 1.0-µm lm of phase G3 

Temperatures 

Injection port: 250° 

Detector: 280° 

Column: See Table 2. 

Table 2 

Carrier gas: Helium 

Flow rate: 9 mL/min 

Injection volume: 1 µL 

Injection type: Split; split ratio 1:10 

System suitability 

Sample: System suitability solution 

[Note—See Table 3 for the relative retention times.] 

Suitability requirements 

Peak-to-valley ratio:   NLT 15 between sertraline related compound A and sertraline  Analysis 

Sample: Sample solution 

Calculate the percentage of each individual impurity in the portion of Sertraline Hydrochloride taken: 

Result = (r_U/r_T ) × 100 

r_U = peak response of each individual impurity from the Sample solution

r_T = sum of all the peak responses from the Sample solution  

Acceptance criteria: See Table 3. The reporting threshold is 0.05%.  

Table 3 

a(1RS,4RS)-4-Phenyl-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine. 

b(1RS,4RS)-4-(4-Chlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine. 

c(1RS,4RS)-4-(3-Chlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine. 

d 4-(3,4-Dichlorophenyl)-3,4-dihydronaphthalen-1(2H)-one. 

e Does not include mandelic acid and 1R,4R-sertraline hydrochloride.   

Change to read: 

Limit of Mandelic Acid 

Perform this test only if Organic Impurities, Procedure 2, is used. 

Solution A: Dissolve 1 g of sodium dodecyl sulfate  in 800 mL of water. Add 200 mL of acetonitrile and 1 mL of phosphoric acid. 

Solution B: Dissolve 1 g of sodium dodecyl sulfate  in 100 mL of water. Add 900 mL of acetonitrile and 1 mL of phosphoric acid. 

Diluent: Solution A and Solution B (50:50) 

Mobile phase: See Table 4. 

Table 4 

System suitability solution: 0.005 mg/mL each of USP Benzoic Acid RS and USP Mandelic Acid RS in Diluent 

Standard solution: 0.002 mg/mL of USP Mandelic Acid RS in Diluent 

Sample solution: 1 mg/mL of Sertraline Hydrochloride in Diluent 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 220 nm 

Column: 4.6-mm × 25-cm; 3-µm packing L1 

Flow rate: 1 mL/min 

Injection volume: 10 µL 

System suitability 

Samples: System suitability solution and Standard solution 

[Note—The relative retention times for mandelic acid, benzoic acid, and sertraline are 0.2, 0.3, and 1.0 respectively.] Suitability requirements 

Resolution: NLT 5 between benzoic acid and mandelic acid, System suitability solution 

Relative standard deviation: NMT 5.0%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of mandelic acid in the portion of Sertraline Hydrochloride taken: 

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response of mandelic acid from the Sample solution  

r_S = peak response of mandelic acid from the Standard solution 

C_S = concentration of USP Mandelic Acid RS in the Standard solution (mg/mL) 

C_U = concentration of Sertraline Hydrochloride in the Sample solution (mg/mL) 

Acceptance criteria: NMT 0.2% 

5 SPECIFIC TESTS 

Water Determination 〈921〉, Method I, Method Ia: NMT 0.50% 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in tight, light-resistant containers at a temperature NMT 40°. 

Labeling: Label to indicate the Organic Impurities procedure with which the article complies, if Organic Impurities, Procedure 1, is not used. Change to read: 

USP Reference Standards 〈11〉 

USP Benzoic Acid RS 

USP Mandelic Acid RS 

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 

USP Sertraline Hydrochloride Related Compound A RS 

(1RS,4SR)-4-(3,4-Dichlorophenyl)-N-methyl-1,2,3,4-tetrahydro-1-naphthylamine hydrochloride. 

C₁₇H₁₇Cl₂N. HCl 342.69