USP(盐酸舍曲林片）

5536 Sertraline / Official Monographs First Supplement to USP 35±NF 30 Analysis Standard solution: 0.05 mg/mL of USP Sertraline Hy- Samples: Standard solution and Sample solution drochloride RS in Mobile phase Calculate the percentage of each individual impurity Sample stock solution: 0.5 mg/mL prepared as follows. (other than process related) in the portion of Tablets Transfer NLT 10 Tablets to a suitable volumetric flask. taken: Dissolve in 0.1% phosphoric acid equivalent to 50% of the volume of the flask. Sonicate for 15 min with inter- Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100 mittent shaking to disperse the Tablets. Add an amount of methanol equivalent to 40% of the volume of the rU = peak response of each individual impurity flask, and continue to sonicate for an additional 10 min. from the Sample solution Cool the solution, and dilute with methanol to volume. rS = peak response of sertraline from the Standard Sample solution: 0.05 mg/mL in Mobile phase from the solution Sample stock solution. Pass a portion of this solution CS = concentration of USP Sertraline Hydrochloride through a nylon filter of 0.45-µm or finer pore size, dis- RS in the Standard solution (mg/mL) card the first few mL, and collect the rest of the filtrate. CU = nominal concentration of sertraline in the Chromatographic system Sample solution (mg/mL) (See Chromatography 〈621〉, System Suitability.) Mr1 = molecular weight of sertraline, 306.23 Mode: LC Mr2 = molecular weight of sertraline hydrochloride, Detector: UV 210 nm 342.69 Column: 4.6-mm × 25-cm; 5-µm packing L10 Acceptance criteria Column temperature: 30° [NOTEÐDisregard any peak below 0.1%.] Flow rate: 1.5 mL/min Individual impurities: NMT 0.2% of any individual Injection volume: 10 µL impurity Run time: Twice the retention time of sertraline Total impurities: NMT 2.0% System suitability Sample: Standard solutionADDITIONAL REQUIREMENTS Suitability requirements • PACKAGING AND STORAGE: Preserve in well-closed Tailing factor: NMT 2.0containers, and store at controlled room temperature. Relative standard deviation: NMT 1.0% Analysis Samples: Standard solution and Sample solutionAdd the following: Calculate the percentage of sertraline (C17H17Cl2N) in the portion of Tablets taken:·• LABELING: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100not used.·(RB 1-Jun-2011) • USP REFERENCE STANDARDS 〈11〉 rU = peak response from the Sample solutionUSP Sertraline Hydrochloride RS rS = peak response from the Standard solutionUSP Sertraline Hydrochloride Racemic Mixture RS CS = concentration of USP Sertraline Hydrochloride(1RS,4RS)-4-(3,4-Dichlorophenyl)-N-methyl-1,2,3,4- RS in the Standard solution (mg/mL)tetrahydro-1-naphthylamine hydrochloride. CU = nominal concentration of sertraline in theC17H17Cl2N ´ HCl 342.69 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 Change to read: base PERFORMANCE TESTS . Sertraline ·Hydrochloride·(RB 1-Nov-2011) Change to read:Tablets ·(Title for this monographÐto become official May 1, • DISSOLUTION 〈711〉2014) ·Test 1·(RB 1-Jun-2011)(Prior to May 1, 2014, the current practice of labeling the Medium: Acetate buffer (3.0 g/L of sodium acetatearticle of commerce with the name Sertraline Tablets may trihydrate and 1.6 mL/L of glacial acetic acid. Adjustbe continued.)·(RB 1-Nov-2011) with glacial acetic acid to a pH of 4.5); 900 mL Apparatus 2: 75 rpmDEFINITION Time: 30 min ·Standard stock solution: 0.56 mg/mL of USP Change to read: Sertraline Hydrochloride RS in Medium. A small volume of methanol, not exceeding 5% of the final volume, Sertraline ·Hydrochloride·(RB 1-Nov-2011) Tablets contain an may be used to help solubilize sertraline.·(RB 1-Jun-2011)amount of sertraline hydrochloride equivalent to NLT Standard solution 90.0% and NMT 110.0% of the labeled amount of ser- For Tablets labeled to contain 50 mg, 100 mg, 150 traline free base (C17H17Cl2N). mg, or 200 mg: 0.056 mg/mL in Medium from the Standard stock solutionIDENTIFICATION For Tablets labeled to contain 25 mg: 0.028A. The retention time of the major peak in the Sample mg/mL in Medium from the Standard stock solutionsolution corresponds to that in the Standard solution, as ob- Sample solution: Pass a portion of the solution undertained in the Assay. test through a suitable filter of 0.45-µm pore size. Dilute with Medium, if necessary.ASSAY Mobile phase: Acetonitrile and 0.1% (v/v) phosphoric• PROCEDURE acid (1:3)Mobile phase: Methanol and 0.1% (v/v) phosphoric acid (1:1) Official from August 1, 2012 Copyright (c) 2012 The United States Pharmacopeial Convention. All rights reserved. Accessed from 128.83.63.20 by nEwp0rt1 on Tue Feb 07 00:36:06 EST 2012 First Supplement to USP 35±NF 30 Official Monographs / Sertraline 5537 Chromatographic system L = label claim (mg/Tablet) (See Chromatography 〈621〉, System Suitability.) Mr1 = molecular weight of sertraline, 306.23 Mode: LC Mr2 = molecular weight of sertraline hydrochloride, Detector: UV 210 nm 342.69 Column: 4.6-mm × 25-cm; 5-µm packing L10 D = dilution factor for the Sample solution Column temperature: 40° V = volume of Medium, 900 mL Flow rate: 1.5 mL/min Tolerances: NLT 80% (Q) of the labeled amount of Injection volume: 10 µL for Tablets labeled to sertraline (C17H17Cl2N) is dissolved.·(RB 1-Jun-2011) contain 50 mg, 100 mg, 150 mg, or 200 mg; 20 µL • UNIFORMITY OF DOSAGE UNITS 〈905〉: Meet the for Tablets labeled to contain 25 mg requirements System suitability IMPURITIESSample: Standard solution • ORGANIC IMPURITIESSuitability requirements [NOTEÐUse freshly prepared samples.]Tailing factor: NMT 2.0 Buffer: 2.72 g/L of monobasic potassium phosphate.Relative standard deviation: NMT 2.0% Adjust with triethylamine to a pH of 7.0.Analysis Mobile phase: Methanol, acetonitrile, and BufferSamples: Standard solution and Sample solution (6:3:11). Adjust with triethylamine to a pH of 8.0.Calculate the percentage of sertraline (C17H17Cl2N) System suitability solution: 5 µg/mL of USP Sertralinedissolved: Hydrochloride Racemic Mixture RS and 0.5 mg/mL of USP Sertraline Hydrochloride RS in Mobile phase·Result = (rU/rS) × (CS/L) × (Mr1/Mr2) × D × V × 100·(RB Standard solution: 2.5 µg/mL of USP Sertraline1-Jun-2011) Hydrochloride RS in Mobile phase rU = peak response from the Sample solution Sample solution: [NOTEÐSonicate for about 10 min rS = peak response from the Standard solution with shaking to disperse the Tablets.] Prepare a solution CS = concentration of USP Sertraline Hydrochloride of 0.5 mg/mL of sertraline in Mobile phase from NLT 20 RS in the Standard solution (mg/mL) powdered Tablets. Pass a portion of this solution through L = label claim ·(mg/Tablet)·(RB 1-Jun-2011) a nylon filter of 0.45-µm or finer pore size, discard the Mr1 = molecular weight of sertraline, 306.23 first few mL, and use the filtrate. Mr2 = molecular weight of sertraline hydrochloride, Chromatographic system 342.69 (See Chromatography 〈621〉, System Suitability.) D = dilution factor for the Sample solution Mode: LC V = volume of Medium, 900 mL Detector: UV 210 nm Tolerances: NLT 80% (Q) of the labeled amount of Column: 4.0-mm × 25-cm; 5-µm packing L45 sertraline (C17H17Cl2N) is dissolved. Flow rate: 0.7 mL/min·Test 2: If the product complies with this test, the Injection volume: 20 µL labeling indicates that it meets USP Dissolution Test 2. System suitability Medium: pH 4.5 acetate buffer (6.8 g/L of sodium Samples: System suitability solution and Standard acetate trihydrate and 32 mL/L of 2 N acetic acid. solution Adjust with 2 N acetic acid to a pH of 4.5); 900 mL [NOTEÐThe relative retention times for the 1R,4R Apparatus 2: 75 rpm cis-isomer of sertraline and sertraline are 0.9 and 1.0, Time: 45 min respectively.] Standard solution: (L/800) mg/mL of USP Sertraline Suitability requirements Hydrochloride RS in Medium, where L is the label claim Resolution: NLT 1.5 between sertraline and the 1R, in mg/Tablet 4R cis-isomer of sertraline, System suitability solution Sample solution: Pass a portion of the solution under Relative standard deviation: NMT 5%, Standard test through a suitable filter of 0.45-µm pore size. solution Buffer: 3 mL/L of glacial acetic acid and 7 mL/L of Analysis triethylamine in water Samples: Standard solution and Sample solution Mobile phase: Acetonitrile, methanol, and Buffer Calculate the percentage of each individual impurity (10:4:8) (other than process related) in the portion of Tablets Chromatographic system taken: (See Chromatography 〈621〉, System Suitability.) Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100Mode: LC Detector: UV 273 nm rU = peak response of each individual impurityColumn: 3.9-mm × 15-cm; 4-µm packing L1 from the Sample solutionColumn temperature: 30° rS = peak response of sertraline from the StandardFlow rate: 1.0 mL/min solutionInjection volume: 20 µL CS = concentration of USP Sertraline HydrochlorideSystem suitability RS in the Standard solution (mg/mL)Sample: Standard solution CU = nominal concentration of sertraline in theSuitability requirements Sample solution (mg/mL)Tailing factor: NMT 2.0 Mr1 = molecular weight of sertraline, 306.23Relative standard deviation: NMT 2.0% Mr2 = molecular weight of sertraline hydrochloride,Analysis 342.69Samples: Standard solution and Sample solution Acceptance criteriaCalculate the percentage of sertraline (C17H17Cl2N) [NOTEÐDisregard any peak below 0.1%.]dissolved: Individual impurities: NMT 0.2% of any individual impurityResult = (rU/rS) × (CS/L) × (Mr1/Mr2) × D × V × 100 Total impurities: NMT 2.0% rU = peak response from the Sample solution ADDITIONAL REQUIREMENTSrS = peak response from the Standard solution • PACKAGING AND STORAGE: Preserve in well-closedCS = concentration of USP Sertraline Hydrochloride containers, and store at controlled room temperature.RS in the Standard solution (mg/mL) Official from August 1, 2012 Copyright (c) 2012 The United States Pharmacopeial Convention. All rights reserved. Accessed from 128.83.63.20 by nEwp0rt1 on Tue Feb 07 00:36:06 EST 2012 5538 Sertraline / Official Monographs First Supplement to USP 35±NF 30 dard solutions and the Assay preparations as 0.1-mL doseAdd the following: volumes in random order, taking 2±3 s to inject each dose volume and flushing each through the catheter·• LABELING: When more than one Dissolution test is given, with about 0.5 mL of Sodium chloride solution. Make in-the labeling states the Dissolution test used only if Test 1 is jections at about 10-min intervals or when the gallblad-not used.·(RB 1-Jun-2011) der has returned to approximately the initial 2 g of• USP REFERENCE STANDARDS 〈11〉 tension.USP Sertraline Hydrochloride RS [NOTEÐThree injections of each dose level may beUSP Sertraline Hydrochloride Racemic Mixture RS made. As many as three different samples can be(1RS,4RS)-4-(3,4-Dichlorophenyl)-N-methyl-1,2,3,4- tested on the same animal before retiring the animal.]tetrahydro-1-naphthylamine hydrochloride. Calculation: Calculate the potency of each vial (see De-C17H17Cl2N ´ HCl 342.69 sign and Analysis of Biological Assays 〈111〉), using a log transformation, straight-line method with a least-squares fitting procedure, and a test for linearity. Acceptance criteria: 85.0%±125.0% Delete the following: SPECIFIC TESTS • PH 〈791〉 Sample solution: Contents of 1 vial in 5 mL water . Acceptance criteria: 5.0±7.5nSincalide for Injection • PARTICULATE MATTER IN INJECTIONS 〈788〉: Meets the re- quirements for small-volume injectionsDEFINITION • CONSTITUTED SOLUTION: At the time of use, it meets theSincalide for Injection is a sterile, synthetically prepared requirements for Injections 〈1〉, Constituted Solutions.C-terminal octapeptide of cholecystokinin and sodium • BACTERIAL ENDOTOXINS TEST 〈85〉: NMT 83.3 USP Endo-chloride. It contains NLT 85.0% and NMT 125.0% of the toxin Units/µg of sincalidelabeled amount of sincalide (C49H62N10O16S3). • OTHER REQUIREMENTS: It meets the requirements under Injections 〈1〉.ASSAY • PROCEDURE ADDITIONAL REQUIREMENTSTest animals: Select male guinea pigs, each weighing at • PACKAGING AND STORAGE: Preserve in single-dose contain-least 500 g, but restrict selection so that no guinea pig is ers, preferably of Type I glass.more than 30% heavier than the lightest. Withdraw • LABELING: Label it to state that it is to be used within 24food, but not water, from each animal. h after constitution.Sodium chloride solution: Sodium Chloride Injection • USP REFERENCE STANDARDS 〈11〉containing 0.9% of NaCl USP Endotoxin RSStandard Stock solutionA: 10 µg/mL of USP Sincalide USP Sincalide RSn1S (USP35)RS in Sodium chloride solution Standard solutions: 0.0624 µg of sincalide/kg of the an- imal's body weight in each 0.1 mL from Standard Stock solution. Prepare a series of 1-in-2 dilutions of this solu- tion with Sodium chloride solution to contain 0.0312, 0.0156, and 0.0078 µg of sincalide/kg of body weight. Add the following: [NOTEÐOther dose levels may be used if so indicated by the responses obtained in the Procedure.] . Sample Stock solution: Constitute 1 vial of Sincalide for nTacrolimus Injection in a sufficient volume of Water for Injection to obtain a solution having a concentration of about 1 µg of sincalide/mL. Sample solutions: 0.0624 µg of sincalide/kg of the ani- mal's body weight in each 0.1 mL from Sample Stock solution. Prepare a series of 1-in-2 dilutions of this solu- tion with Sodium chloride solution to contain 0.0312, 0.0156, and 0.0078 µg of sincalide/kg of body weight. [NOTEÐOther dose levels may be used if so indicated by the responses obtained in the Procedure.] Analysis: Anesthetize each guinea pig by injecting it, subcutaneously, with 2.25 g of urethane/kg of body weight, administered as a 25% solution. Perform a tra- C44H69NO12 ´ H2O 822.03cheotomy, then expose a jugular vein, and cannulate 15,19-Epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclotricosine-1,7,with a polyethylene catheter. Tie a thin silk line to the 20,21(4H,23H)-tetrone-5,6,8,11,12,13,14,15,16,17,18,19,free pole or fundus of the gallbladder, or attach a thin 24,25,26,26a-hexadecahydro-5,19-dihydroxy-3-[2-(4-hy-hook with connecting silk line to the wall of the fundus. droxy-3-methoxycyclohexyl)-1-methylethenyl]-14,16-Gallbladder contractile responses, transmitted through dimethoxy-4,10,12,18-tetramethyl-8-(2-propenyl)-, mono-the silk line, cause a change in the line tension. Connect hydrate, [3S-[3R*,E(1S*,3S*,4S*)],4S*,5R*,8S*,9E,12R*,-the free end of the silk line to a force transducer, and 14R*,15S*,16R*,18S*,19S*,26aR*]]-; impose on the system an initial tension of about 2 g. (−)-(3S,4R,5S,8R,9E,12S,14S,15R,16S,18R,19R,26aS)-8-Connect the force transducer to a polygraph, which Allyl-5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-records the contractile responses. Determine the sensitiv- hexadecahydro-5,19-dihydroxy-3-[(E)-2-[(1R,3R,4R)-4-ity or the responsiveness of the guinea pig's gallbladder hydroxy-3-methoxycyclohexyl]-1-methylvinyl]-14,16-by making a few trial injections through the jugular vein dimethoxy-4,10,12,18-tetramethyl-15,19-epoxy-3H-pyridocatheter, then select two nonconsecutive dose levels [2,1-c][1,4]oxaazacyclotricosine-1,7,20,21(4H,23H)-te-(e.g., 0.0624 and 0.0156) for the Assay. Use the same trone, monohydrate [109581-93-3].dose levels for the Sample solutions as for the Standard solutions. Administer the selected dose levels of the Stan- Official from August 1, 2012 Copyright (c) 2012 The United States Pharmacopeial Convention. All rights reserved. Accessed from 128.83.63.20 by nEwp0rt1 on Tue Feb 07 00:36:06 EST 2012