Verification and separation method for terfenadine related substance

A technology of terfenadine and related substances, which is applied in the field of drug impurity testing, can solve problems such as not being able to fully and effectively achieve separation, not being able to fully meet the needs of use, and achieve good practical results

Active Publication Date: 2018-06-22
JIANGSU LIANHUAN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

This method can achieve the complete separation of impurities and main components to a certain extent, but when the cont...

Method used

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  • Verification and separation method for terfenadine related substance
  • Verification and separation method for terfenadine related substance
  • Verification and separation method for terfenadine related substance

Examples

Experimental program
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Embodiment 1

[0027] A method for testing and separating related substances of terfenadine, the process is as follows:

[0028] 1) Take appropriate amounts of impurity A, impurity B, impurity C, impurity D, impurity E, impurity F, impurity G, impurity H, impurity I, impurity J, and TFND, and add 70% acetonitrile to make a single solution of 10 μg / mL, Carry out full-wavelength scanning at a wavelength of 190nm to 400nm to obtain the scanning wavelength of each substance, as shown in Table 1 and figure 1 shown.

[0029] Table 1 Wavelength selection result table

[0030]

[0031]

[0032]

[0033] Depend on figure 1 It can be seen that the UV absorption of impurities A, B, C, D, E, F, G, H, I, J, and terfenadine are quite different, but in the detection method specified in the EP standard There is a large absorption at the wavelength (217nm), and the detection wavelength is set at 217nm in combination with the quality standards of the European Pharmacopoeia and the results of ultra...

Embodiment 2

[0039] The inspection separation method of terfenadine related substance, with embodiment 1, wherein, the chromatographic condition in step 2) is as follows:

[0040] Chromatographic column: MZ-ANALYTICAL Column 250*4.6mm 100ODS-3 5μm. Mobile phase A: acetonitrile-phosphate (dissolve 3.58g disodium hydrogen phosphate dodecahydrate in 1000mL water, adjust the pH to 6.0 with phosphoric acid, then add 1.92g SDS to dissolve and filter) = 20︰80; mobile phase B: acetonitrile. Gradient elution: 0min, 60%A, 40%B; 3min, 55%A, 45%B; 20min, 20%A, 80%B. Solvent: acetonitrile-phosphate=45:55. Wavelength: 217nm. Flow rate: 1.0 mL / min. Column temperature: 35°C. Injection volume: 20 μL.

[0041] Inject the mixed solution and record the chromatogram, such as image 3 As shown, the results show that the peak eluting time of each impurity under this condition is reasonable, but the unknown impurity and impurity H cannot be separated well.

Embodiment 3

[0043] The inspection separation method of terfenadine related substance, with embodiment 2, wherein, the chromatographic condition in step 2) is as follows:

[0044] Chromatographic column: MZ-ANALYTICAL Column 250*4.6mm 100ODS-3 5μm. Mobile phase A: acetonitrile-phosphate (dissolve 3.58g disodium hydrogen phosphate dodecahydrate in 1000mL water, adjust the pH to 6.0 with phosphoric acid, then add 1.92g SDS to dissolve and filter) = 20︰80; mobile phase B: acetonitrile-methanol = 95:5. Gradient elution: 0min, 40%A, 60%B; 10min, 40%A, 60%B; 20min, 20%A, 80%B. Solvent: buffer salt (pH6.0)-acetonitrile=40:60. Wavelength: 217nm. Flow rate: 1.0 mL / min. Column temperature: 30°C. Injection volume: 20 μL.

[0045]Take the mixed solution 2 (prepared with the mixed solution 1 of Example 1, add solvent (buffer salt-acetonitrile=40: 60) to prepare about impurity A, impurity B, impurity C, impurity D, impurity E, impurity F per 1mL , impurity G, impurity H, impurity I, impurity J ea...

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Abstract

The invention discloses a verification and separation method for a terfenadine related substance. The method comprises the following steps: 1) respectively putting 70% acetonitrile into impurities anda proper amount of TFND (Terfenadine) so as to obtain a 10mu g/mL single solution, performing full-wavelength scanning at wavelengths of 190-400nm so as to obtain scanning wavelengths of different substances, and confirming ultraviolet scanning detection wavelengths; 2) preparing a mixed solution for detection; 3) setting the following spectrum conditions: a spectrum column: MZ-NALYTICAL Column of 250*4.6mm 100ODS 5mu m; a mobile phase A: acetonitrile and phosphate in a ratio of 20:80; a mobile phase B: acetonitrile; gradient elution: 0 minute, 60%A, 40% B, 3 minutes, 55%A, 45%B, 20 minutes,20% A and 80%B; a solvent of acetonitrile and phosphate in a ratio of 45:55; a wavelength of 217nm; a flowing velocity of 1.0mL/minute; a column temperature of 30-35 DEG C; a sampling amount of 20mu L; 4) feeding the mixed solution as a sample, recording chromatogram, and separating both terfenadine and different impurities. By adopting the method, the separation degree of the terfenadine and theimpurities is greater than 5.0, the separation degrees among the impurities and between other known impurities and the terfenadine are both greater than 1.5, in addition, the separation degree of a main peak and unknown impurities can be up to 3.5, and requirements can be met.

Description

technical field [0001] The invention belongs to the technical field of drug impurity testing, and in particular relates to a testing method for related substances of terfenadine. Background technique [0002] Terfenadine is the main ingredient of Terfenadine Granules (trade name: Mitel), which is used for the treatment of seasonal and non-seasonal allergic rhinitis, urticaria and hay fever. Terfenadine is a specific H1 receptor blocker. Under the effective dose of antihistamine, terfenadine and its metabolites are not easy to pass through the blood-brain barrier, so it rarely has central inhibitory effect. [0003] Terfenadine (Terfenadine) was created by Carr et al. in 1973, and was first launched in 1981 by Merrell Pharmaceutical Company of the United States. It has been widely used in European and American countries at present. The Chinese Pharmacopoeia 2010 Edition does not provide for the testing of related substances in the tablet, and in other countries in the world,...

Claims

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Application Information

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IPC IPC(8): G01N30/02
CPCG01N30/02
Inventor 田娟曹元敏
Owner JIANGSU LIANHUAN PHARMA
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