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Detector combined method for measuring impurities of repaglinide in repaglinide metformin tablets

A metformin tablet and detector technology, which is applied in the direction of instruments, measuring devices, scientific instruments, etc., can solve the problems that the response cannot be completely eliminated, the accuracy and precision are affected, and the specificity of the method is reduced.

Inactive Publication Date: 2019-06-14
SHANDONG ACADEMY OF PHARMACEUTICAL SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Though this method uses acetonitrile as solvent solvent, metformin hydrochloride still has certain solubility in acetonitrile, can't get rid of its response in chromatogram completely.
As can be seen from the spectrum in the text, the negative sample solution is very close to the peak position of the impurity A (i.e. impurity 1 in the present invention) described in the text, which reduces the specificity of the method; To the concentration of the sample to be tested in the article, a small amount of solution is required to dissolve a large amount of solid powder, which will affect the accuracy and precision of the method

Method used

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  • Detector combined method for measuring impurities of repaglinide in repaglinide metformin tablets
  • Detector combined method for measuring impurities of repaglinide in repaglinide metformin tablets
  • Detector combined method for measuring impurities of repaglinide in repaglinide metformin tablets

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Instrument: Agilent1260 high performance liquid chromatography (G1329B autosampler, G1316A constant temperature column oven, G1311C quaternary pump, G4212B diode array detector, G1321B fluorescence detector).

[0046] Chromatographic column: AgelaVENUSIL ASB C18 chromatographic column (4.6mm×250mm, 5μm).

[0047] Mobile phase: 0.4% potassium dihydrogen phosphate buffer solution (adjusted to pH 3.2 with phosphoric acid) as mobile phase A and acetonitrile as mobile phase B, using gradient elution for separation. Gradient elution was performed according to Table 2.

[0048] Table 2 gradient elution table (volume ratio) / %

[0049]

[0050] Detector: diode array and fluorescence detector connected in series, the detection wavelength is 240nm, the excitation wavelength is 244nm, and the emission wavelength is 348nm.

[0051] Flow rate: 1.0ml / min, injection volume: 50μl, column temperature: 40°C.

[0052] Sample solution preparation diluent: ethanol-water (volume ratio 1...

Embodiment 2

[0058] Embodiment 2 specificity test

[0059] In the present invention, the compound repaglinide metformin tablet has been subjected to a forced destruction degradation test, which is destroyed by means of strong light irradiation, high temperature, acid, alkali hydrolysis and oxidation to study the separation degree of degradation impurities and main peaks, and detects in a diode array The peak purity of the main peak was verified in the instrument to prove the specificity of the method. Take 20 tablets of compound repaglinide metformin tablets, grind them into powder, weigh the tablet powders to prepare the following solutions.

[0060] a. Sample solution: Weigh an appropriate amount of tablet powder (approximately equivalent to 0.5mg repaglinide), put it in a 50ml measuring bottle, add diluent to dissolve repaglinide and reach the scale, shake well, filter, and take the continued filtrate as a sample solution.

[0061] b. Acid-destroyed sample solution: Weigh an appropria...

Embodiment 3

[0070] Embodiment 3 detection limit test

[0071] Take an appropriate amount of repaglinide and its impurities 1, 2, 3, 4, and 5, weigh them accurately, dissolve them with a diluent and dilute them into a series of solutions, inject samples for determination, and take the concentration point with a signal-to-noise ratio ≥ 3 As the limit of detection, the result is:

[0072] The detection limits of repaglinide, impurity 1, impurity 2, impurity 3, impurity 4, and impurity 5 were 0.06ng, 0.07ng, 0.05ng, 0.2ng, 0.1ng, and 0.06ng, respectively, and the detection limits of each impurity were within the main component 0.05 % concentration below, to meet the impurity detection sensitivity requirements.

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Abstract

The invention belongs to the field of pharmaceutical analysis. Five kinds of impurities of repaglinide in repaglinide metformin tablets are separated and measured by a technology of a high performanceliquid chromatography with two detectors in series. According to the chromatography, octyl silane bonded silica gel is used as a filling agent; monopotassium phosphate buffer solution (the mass fraction is 0.1%-1% and the pH value is 2.0-8.0)-acetonitrile is used as the mobile phase; the detectors are a diode array and a fluorescence detector in series, the detection wavelength is 210-310nm, theexcitation wavelength is 200nm-300nm, and the emission wavelength is 300-400nm; and the flow rate is 0.5-2.0ml / min, the injection volume is 10-100[mu]l, and the sample solution concentration is 0.01-1.0mg / ml. By using the method, the five kinds of the impurities of repaglinide in repaglinide metformin tablets can be calculated accurately and quantificationally, and the quality controllability of the repaglinide metformin tablets is ensured.

Description

technical field [0001] The invention belongs to the field of drug analysis, in particular to a method for separating and measuring repaglinide impurities in compound repaglinide metformin tablets by high performance liquid chromatography. Background technique [0002] Repaglinide and metformin tablets are repaglinide and metformin hydrochloride compound preparations, developed by Novo Nordisk, approved by the FDA on June 23, 2008, and listed in the United States under the trade name Currently not listed in the country. This product is used for the treatment of type 2 diabetes (non-insulin dependent) whose hyperglycemia cannot be effectively controlled by diet control and exercise. The component of repaglinide is an insulin secretagogue, which is a derivative of methylaminobenzoic acid (CMBA) , which promotes the ATP-dependent K + Channel closed, inhibiting K + Efflux from β-cells depolarizes the membrane and thus opens voltage-dependent Ca 2+ channels that allow extrace...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02G01N30/74G01N30/86
Inventor 张琳刘葵葵王伶李欣邢学敏
Owner SHANDONG ACADEMY OF PHARMACEUTICAL SCIENCES
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