阅读说明：本技术 一种吡拉西坦的有关物质及其分析检测方法 (Piracetam related substance and analytical detection method thereof ) 是由 朱怡君 孙忠华 王兵 于 2020-04-02 设计创作，主要内容包括：本发明公开了一种吡拉西坦的有关物质、制备方法及其分析方法,该有关物质为首次报道,制备方法操作简便可行。本发明提供的分析方法可有效分离有关物质与吡拉西坦,能有效提高产品质。(The invention discloses a piracetam related substance, a preparation method and an analysis method thereof, wherein the related substance is reported for the first time, and the preparation method is simple and feasible to operate. The analysis method provided by the invention can effectively separate related substances and piracetam and can effectively improve the yield and quality.)

1. A piracetam photodegradation compound of formula (1) has a structure

2. A process for the preparation of a compound according to claim 1, comprising the steps of:

(1) preparation of a light damage sample: the piracetam is damaged and degraded by illumination, and is irradiated by ultraviolet light and then by a fluorescent lamp;

(2) and (3) enrichment of degradation products: dissolving the products damaged by illumination in water, adding methanol to precipitate solids, and performing suction filtration to obtain crude products of degradation products;

(3) and (3) purifying degradation products: and (3) purifying the crude degradation product by silica gel column chromatography, and purifying by using dichloromethane: eluting with methanol (5:1), and concentrating to obtain product 1.

3. The method for preparing the compound according to claim 2, wherein the light damage method in the step (1) is irradiating for 12-16h by an ultraviolet fluorescent lamp of 240W/m and then irradiating for 10-15h by a fluorescent lamp of 120 ten thousand L x.

4. A process for the preparation of a compound according to claim 2, characterized in that: the mass-to-volume ratio of the photodisruption product to water in the step (2) is 1 g: (1-5 ml).

5. A method for assaying a compound according to claim 1, characterized in that it comprises the following conditions:

chromatographic column Agilent extended-C18 (4.6mm × 250mm, 5 μm);

mobile phase: methanol-water (10: 90);

the flow rate of the mobile phase is 1.0m L/min;

detection wavelength: 210nm

Column temperature: 40 ℃;

the sample size is 10 mu L.

Technical Field

The invention relates to the technical field of pharmacy, in particular to a piracetam related substance, and a preparation method and an analysis and detection method of the related substance.

Background

Piracetam (Piracetam) is a 4-aminobutyric acid derivative, available under the trade name brain rehabilitation. The drug was first researched and synthesized by UCB institute of Belgium in 1963, marketed in 1971, introduced in 70 s in China, and first imitated successfully by the northeast pharmaceutical Co-Ltd in 1980. Researches show that the piracetam has the effects of activating, protecting and repairing nerve cells, is a medicine and an intelligence promoting medicine acting on a central nervous system, and has obvious improvement effects on hypomnesis, mild and moderate brain dysfunction, senile dementia, children intelligence development retardation and the like caused by various reasons.

The structural formula is as follows:

the currently reported synthetic methods of piracetam are more, but the industrialization is also the route published by CN 1094485: prepared by condensation and ammonolysis of pyrrolidone and chloroacetate serving as starting materials.

Disclosure of Invention

In the stability investigation of the piracetam injection, the inventor unexpectedly discovers the phenomena of product content reduction and purity reduction under the illumination condition, and the reason for the phenomenon is probably that the piracetam generates a byproduct through a photodegradation reaction under a specific environment. The inventor further increases the destructive test intensity, enriches byproducts, and discovers two novel compounds which are not reported in the prior art through separation and structure confirmation.

The invention also aims to provide a preparation and analysis method of the piracetam photodegradation product, which can be effectively used for detecting related substances of piracetam and injection thereof, is beneficial to improving the quality standard of piracetam and injection thereof and improving the medication safety of people.

In order to achieve the above purpose, the invention provides the following technical scheme: a photodegradation product of piracetam having the following chemical formula:

the invention provides a preparation method of the piracetam photodegradation product, which comprises the following steps:

(1) illumination damage sample preparation, namely, performing illumination damage degradation on piracetam (10g), irradiating for 12-16h by ultraviolet light of 240 watt-hour/square meter, and then irradiating for 10-15h by a fluorescent lamp of 120 ten thousand L x;

(2) and (3) enrichment of degradation products: dissolving the photo-damage product (9g) in water (10ml), adding methanol (50ml) to precipitate a solid, and performing suction filtration to obtain a crude product, wherein the mass volume ratio of the photo-damage product to the water is 1 g: (1-5ml), preferably 1 g: (1-2 ml);

(3) and (3) purifying degradation products: and (3) purifying the crude degradation product by silica gel column chromatography, and purifying by using dichloromethane: eluting with methanol (5:1), and concentrating to obtain the final product.

The invention provides a liquid phase analysis and detection method of the piracetam photodegradation product, which comprises the following parameters:

chromatographic column Agilent extended-C18 (4.6mm × 250mm, 5 μm);

mobile phase: methanol-water (10: 90);

the flow rate of the mobile phase is 1.0m L/min;

detection wavelength: 210nm

Column temperature: 40 ℃;

the sample size is 10 mu L.

Under the chromatographic conditions, the photodegradation product can be completely separated from the piracetam, and can be used as a reference substance in piracetam related substance examination.

The invention has the following beneficial effects:

(1) the invention provides a photodegradable substance of piracetam, which is reported for the first time and belongs to a new compound, and the preparation method of the photodegradable product is simple and feasible, good in reaction reproducibility and high in yield;

(2) the liquid phase analysis method provided by the invention can quickly detect the degradation product, the chromatographic peak and piracetam chromatographic peak separation degree is more than 2.0, the degradation product and piracetam can be effectively distinguished, and a stable and reliable piracetam injection analysis method can be provided.

Drawings

FIG. 1 is a chart showing the assignment of hydrogen spectra data of photodegradation products according to the present invention;

FIG. 2 is a chart showing the CMS data assignment of the photodegradation product L according to the present invention.

FIG. 3 is a liquid chromatogram of the photodegradation product of the present invention and piracetam.

Detailed Description

The technical solutions of the present invention will be described clearly and completely with reference to the following detailed description, but those skilled in the art will understand that the following described examples are some, not all, of the examples of the present invention, and are only used for illustrating the present invention, and should not be construed as limiting the scope of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.