Related substance analysis method of terazosin hydrochloride tablets

A technology of terazosin hydrochloride tablets and related substances, which is applied in the field of analysis and detection of related substances of terazosin hydrochloride tablets, can solve problems such as no reports of terazosin hydrochloride tablets, and achieve qualified inspection and peak purity , high yield effect

Active Publication Date: 2016-07-13

南京易亨制药有限公司

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AI-Extracted Technical Summary

Problems solved by technology

[0007] At present, there are no reports of other impuriti...

Abstract

The invention discloses a related substance analysis method of terazosin hydrochloride tablets. A related substance is reported for the first time. A preparation method comprises the following steps: damaging a terazosin hydrochloride crude drug under the condition of 80 DEG C to 90 DEG C for 36 to 48 hours; dissolving the sample which is damaged at the high temperature into a methanol-water solution with the methanol volume percent concentration of 70 percent to 90 percent; stirring and filtering through suction; collecting filtrate, and decompressing and concentrating to obtain a concentrate; carrying out chromatographic separation on the concentrate with a normal-phase silica gel column, and carrying out gradient elution with a chloroform-methanol mixed solvent at the volume ratio of (5:1) to (2:1); collecting 8th to 14th column volume eluting solutions and concentrating to obtain a rough product; purifying the rough product with a reversed-phase silica gel column, wherein a fixed phase is octadecyl silane bonded silica gel and a mobile phase is acetonitrile-water with the acetonitrile volume percent concentration of 80 percent to 90 percent; carrying out gradient elution and collecting 7th to 11th column volume eluting solutions, and concentrating, freezing and drying. The preparation method is simple and feasible. The liquid-phase analysis method provided by the invention can be used for effectively separating the chromatographic peak of the related substance and the chromatographic peak of terazosin.

Application Domain

Organic chemistryComponent separation

Technology Topic

SolventChemistry +14

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Examples

Experimental program(4)
Effect test(1)

Example Embodiment

[0038] Example 1: Preparation and structural confirmation of related substances

[0039] Take 10g terazosin hydrochloride raw material evenly spread it in a petri dish, place it in an oven, and destroy it at 85°C for 42 hours. Then, the high-temperature damaged sample was dissolved in a methanol-water solution with a methanol volume percentage of 80%, stirred for 20 minutes, filtered with a suction funnel, collected the filtrate, and concentrated under reduced pressure to obtain a concentrate of 6.2g; then the concentrate was used Dissolve in 8ml methanol, mix with 8g normal phase silica gel with a particle size of 100-200 mesh, evaporate the solvent, use 120g normal phase silica gel with a particle size of 200-300 mesh as the separation silica gel for column chromatography, use chloroform with a volume ratio of 7:2 -Isocratic elution with methanol mixed solvent, collect the 11th column volume eluent, concentrate under reduced pressure to obtain 4.8g crude product; then dissolve the crude product in acetonitrile aqueous solution with 85% volume percentage of acetonitrile, and purify with reversed-phase silica gel column , The stationary phase is octadecylsilane-bonded silica gel, and the mobile phase is acetonitrile-water with a volume percentage of acetonitrile 85%, isocratic elution, collect the eluate of the 9th column volume, concentrate under reduced pressure, and freeze 3.5 g of light yellow powder was obtained after drying. HPLC normalized purity is greater than 98%.

[0040] Structure confirmation:

[0041] Light yellow powder, easily soluble in acetone and methanol; HR-ESIMS shows [M+H] + It is m/z418.1714, combined with nuclear magnetic characteristics, the molecular formula is C 19 H 23 N 5 O 6. Proton spectrum data and attribution see figure 1 (ppm,methanol-d 4 ,500MHz); see carbon spectrum data and attribution figure 2 (ppm,methanol-d 4 ,150MHz). Combining mass spectrometry and nuclear magnetic data, combined with the structure confirmation data of terazosin, it can be confirmed that the chemical structure of the substance is as follows:

[0042]

Example Embodiment

[0043] Example 2: Preparation of related substances

[0044] Take 10g terazosin hydrochloride raw material evenly spread it in a petri dish, put it in an oven, and destroy it at 80°C for 48 hours. Then, the high-temperature damaged sample was dissolved in methanol-water solution with a methanol volume percentage of 70%, stirred for 20 minutes, filtered with a suction funnel, collected the filtrate, and concentrated under reduced pressure to obtain a concentrate of 6.1g; then the concentrate was used Dissolve in 8ml methanol, mix the sample with 8g normal phase silica gel with a particle size of 100-200 mesh, evaporate the solvent, use 120g normal phase silica gel with a particle size of 200-300 mesh as the separation silica gel for column chromatography, use chloroform with a volume ratio of 5:1 -Isocratic elution with methanol mixed solvent, collect the 14th column volume eluate, concentrate under reduced pressure to obtain the crude product 4.5g; then dissolve the crude product with acetonitrile aqueous solution with a volume percentage of acetonitrile of 80%, and purify with a reversed-phase silica gel column , The stationary phase is octadecylsilane-bonded silica gel, the mobile phase is acetonitrile-water with a volume percentage of acetonitrile of 80%, isocratic elution, collect the 11th column volume of the eluate, concentrate under reduced pressure, and freeze 3.2 g of light yellow powder was obtained after drying. HPLC normalized purity is greater than 98%.

Example Embodiment

[0045] Example 3: Preparation of related substances

[0046] Take 10g terazosin hydrochloride raw material evenly spread in a petri dish, put it in an oven, and destroy it at 90°C for 36 hours. Then, the high-temperature damaged sample was dissolved in a methanol-water solution with a methanol volume percentage of 90%, stirred for 20 minutes, filtered with a suction funnel, collected the filtrate, and concentrated under reduced pressure to obtain a concentrate of 6.4g; then the concentrate was used Dissolve in 8ml methanol, mix the sample with 8g normal phase silica gel with a particle size of 100-200 mesh, evaporate the solvent, use 120g normal phase silica gel with a particle size of 200-300 mesh as separation silica gel for column chromatography, use chloroform with a volume ratio of 2:1 -Isocratic elution with methanol mixed solvent, collect the 8th column volume eluent, concentrate under reduced pressure to obtain 4.9g crude product; then dissolve the crude product in acetonitrile aqueous solution with a volume percentage of acetonitrile of 90%, and purify with a reversed-phase silica gel column , The stationary phase is octadecylsilane-bonded silica gel, the mobile phase is acetonitrile-water with a volume percentage of acetonitrile of 90%, isocratic elution, collect the eluate of the seventh column volume, concentrate under reduced pressure, and freeze 3.7 g of light yellow powder was obtained after drying. HPLC normalized purity is greater than 98%.

PUM

Property	Measurement	Unit
Wavelength	246.0	nm

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Related substance analysis method of terazosin hydrochloride tablets

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Abstract

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Description & Claims & Application Information

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