Liquid chromatographic method for separating and determining multiple impurities in tolvaptan

A technology of tolvaptan and high-performance liquid chromatography, applied in the field of drug analysis, to achieve the effects of improved safety, strong specificity, and accurate and reliable determination results

Active Publication Date: 2015-10-28
CHENGDU BAIYU PHARMA CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, there are no relevant reports on the detection methods of the positional isomer impuritie

Method used

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  • Liquid chromatographic method for separating and determining multiple impurities in tolvaptan
  • Liquid chromatographic method for separating and determining multiple impurities in tolvaptan
  • Liquid chromatographic method for separating and determining multiple impurities in tolvaptan

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[0060] Example 1 Detection conditions of the present invention

[0061] High performance liquid chromatograph: LC-20AT, SPD-20A

[0062] Column: Symmetry shield TM RP18 (4.6×150mm, 5μm);

[0063] Mobile phase: acetonitrile-water (containing 0.2% phosphoric acid) (45:55);

[0064] Flow rate: 1.0mL / min;

[0065] Detection wavelength: 254nm;

[0066] Column temperature: 25℃;

[0067] Injection volume: 10 μL.

[0068] Detection steps:

[0069] Take an appropriate amount of the reference substances of impurities II, III, IV, V and VI, dissolve them in methanol, and prepare a reference substance solution containing about 6.0 μg per 1 mL

[0070] Determination method: Take 10 μL of the above solution and inject it into a liquid chromatograph, record the chromatogram, and the results are as follows figure 1 shown. The chromatographic peak separation degree of impurity II and impurity III in the spectrum is 1.518; the chromatographic peak separation degree of impurity V and i...

Example Embodiment

[0119] Example 2 Detection of tolvaptan and its impurities

[0120] Detection conditions:

[0121] High performance liquid chromatograph: LC-20AT, SPD-20A

[0122] Column: Symmetry shield TM RP18 (4.6×150mm, 5μm);

[0123] Mobile phase: acetonitrile-water (containing 0.2% phosphoric acid) (45:55);

[0124] Flow rate: 1.0mL / min;

[0125] Detection wavelength: 254nm;

[0126] Column temperature: 25℃;

[0127] Solvent: methanol;

[0128] Injection volume: 10 μL.

[0129] a. Take 10 mg of tolvaptan I (crude product), put it in a 10 mL measuring bottle, dissolve it with a solvent and dilute to the mark, as the test solution;

[0130] b. Take appropriate amount of impurities II, III, IV, V and VI reference substance, dissolve and dilute with solvent respectively to prepare reference substance solution with a concentration of about 1.0μg / mL;

[0131] C, get the need testing solution of step a and the reference substance solution of step b respectively, inject high performance...

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Abstract

The invention discloses a liquid chromatographic method for separating and determining multiple impurities in tolvaptan. High performance liquid chromatographic detection conditions are that detection wavelength is 230 to 280 nm, a chromatographic column is Symmetry shield RP18 and a mobile phase is acetonitrile-aqueous solution containing 0.2% phosphoric acid, wherein the volume fraction of acetonitrile is 43 to 47%. The method provided by the invention overcomes problems in separation and determination of tolvaptan and five impurities thereof, especially problems in separation and determination of positional isomer impurities of tolvaptan and positional isomer impurities of tolvaptan intermediates; and the method has the advantages of good specificity, simplicity, rapidness, accuracy and accurate and reliable determination results, so the quality of tolvaptan can be effectively monitored, and drug security is improved.

Description

technical field [0001] The invention belongs to the field of drug analysis, in particular to a liquid chromatography method for separating and measuring multiple impurities in tolvaptan. Background technique [0002] Tolvaptan (Tolvaptan trade name: Samsca), chemical name N-[4-[(5RS)-7-chloro-5-hydroxy-2,3,4,5-tetrahydro-1H-benzo[b ]azepine-1-formyl]-3-methylphenyl]-2-methylbenzamide (molecular weight: C 26 h 25 ClN 2 o 3 ), whose chemical structural formula is shown in formula I, is an oral selective non-peptide novel arginine vasopressin V2 receptor antagonist developed by Otsuka Pharm. The US FDA approved it in May 2009 for the treatment of hypercapacity or isovolumic hyponatremia (serum sodium < 125 mg) caused by congestive heart failure (CHF), liver cirrhosis, and antidiuretic hormone insufficiency syndrome. / L, or mild symptoms). Oral administration of tolvaptan tablets can significantly reduce the patient's body weight and edema without disrupting the blood e...

Claims

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Application Information

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IPC IPC(8): G01N30/02
Inventor 夏玉立孙毅
Owner CHENGDU BAIYU PHARMA CO LTD
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