WO2019192268A1 - Method for identifying chiral drug based on terahertz time domain spectrometer - Google Patents

Abstract

The present invention relates to a method for identifying a chiral drug based on a Terahertz time domain spectrometer. The method comprises: preparing a dextroisomer sample, a laevoisomer sample and a mixture sample of a chiral drug; testing absorption spectrums of the dextroisomer sample, the laevoisomer sample, the mixture sample, and a sample to be tested respectively using the Terahertz time domain spectrometer to obtain a dextroisomer absorption spectrum, a laevoisomer absorption spectrum, a mixture absorption spectrum and a tested absorption spectrum respectively; and analyzing the tested absorption spectrum according to the dextroisomer absorption spectrum, the laevoisomer absorption spectrum and the mixture absorption spectrum to identify whether the sample to be tested meets the requirements. According to the method, spectrum absorption information of the sample for Terahertz frequency bands can be obtained and whether the sample to be tested meets the requirements can be known by contrasting absorption spectrums of several standard samples of the chiral drug. Therefore, the described testing method is efficient and accurate for testing a chiral drug.

Description

Method for identifying chiral drugs based on terahertz time domain spectrometer Technical field

The invention relates to a drug testing technology, in particular to a method for identifying chiral drugs based on a terahertz time domain spectrometer.

Background technique

Chiral drug refers to the introduction of a pair of enantiomers which are mutually physical and mirror images after the introduction of a chiral center in the molecular structure of the drug. Most of the drugs currently used are chiral drugs. The pharmacological action of chiral drugs is achieved by strict chiral matching and molecular recognition with macromolecules in vivo. There is a significant difference in the pharmacological activity, metabolic processes and toxicity of a pair of corresponding isomers of chiral drugs in humans.

A pair of enantiomers of chiral drugs often have different pharmacological activities and toxicity, and their roles in the clinic are also different. At present, it is generally required in medicine to use chiral drugs in a pure single isomer form in clinical practice to achieve the desired therapeutic effect. However, there are some illegal pharmaceutical companies in the market that incorporate the isomers of standard ingredients in medicines to reduce costs, but the curative effect is very different from the qualified drugs, and even has toxicity. Therefore, the regulatory authorities need to test the chiral drugs entering the market.

At present, the traditional identification methods for chiral drugs are mainly gas chromatography and liquid chromatography. The above methods have problems in that the identification results of chiral drugs are not ideal.

Summary of the invention

Based on this, it is necessary to provide a method for identifying chiral drugs based on terahertz time domain spectrometer for the problem that the traditional identification method has unsatisfactory identification results.

A method for identifying chiral drugs based on a terahertz time domain spectrometer, comprising:

Preparing a right-handed body sample, a left-handed body sample, and a mixed body sample of the chiral drug; wherein the mixed body sample contains a left-handed body and a right-handed body of the chiral drug;

Measuring, by the terahertz time domain spectrometer, absorption spectra of the right-handed body sample, the left-handed body sample, the mixed body sample, and the sample to be tested, respectively, to obtain a right-handed absorption spectrum, a left-handed absorption spectrum, Mixed absorption spectrum, test absorption spectrum;

The test absorption spectrum is analyzed according to the right-handed absorption spectrum, the left-handed absorption spectrum, and the mixture absorption spectrum to identify whether the sample to be tested meets the requirements.

The above method for identifying a chiral drug based on a terahertz time-domain spectrometer firstly prepares a mixture of a right-handed body sample, a left-handed body sample, and a mixture of a right-handed body and a left-handed body, that is, a right-handed body sample, a left-handed body sample, and Mix body samples. Secondly, the absorption spectra of the right-handed sample, the left-handed sample and the mixed body sample were tested by terahertz time-domain spectrometer, and the right-handed absorption spectrum, the left-handed absorption spectrum and the mixed absorption spectrum were obtained. When testing chiral drugs, the absorption spectrum of the sample to be tested is tested by a terahertz time domain spectrometer to obtain a test absorption spectrum. Then, based on the right-handed absorption spectrum, the left-handed absorption spectrum, and the mixed absorption spectrum, the test absorption spectrum is used to identify whether the sample to be tested meets the requirements. Thus, the above method obtains the spectral absorption information of the sample on the terahertz band, and the absorption spectrum of several standard samples of the chiral drug can be used to obtain whether the sample to be tested meets the requirements. Therefore, the above test method is effective and accurate for testing chiral drugs.

In one embodiment, the steps of preparing the right-handed sample, the left-handed body sample, and the mixed body sample of the chiral drug include:

Drying the standard of the right-handed body of the chiral drug and the standard of the left-handed body;

The standard of the right-handed body and the standard of the left-handed body are respectively developed into a powder form;

A preset weight percentage of the right-handed body sample, the left-handed body sample, and the mixed body sample are separately prepared.

In one embodiment, the step of respectively preparing the preset weight percentage of the right-handed body sample, the left-handed body sample, and the mixed-body sample further comprises:

The right-handed body sample, the left-handed body sample, and the mixed body sample were respectively pressed into a disk-like structure.

In one embodiment, the thickness of the right-handed body sample, the left-handed body sample, and the mixed body sample are all in the range of 1.5 mm to 2 mm.

In one embodiment, the weight percentage of the right-handed body in the right-handed body sample is in the range of 20% to 30%; and the weight percentage of the left-handed body in the left-handed body sample is 20% to 30% Within the range of %; and

The weight percentage of the mixture of the left-handed body and the right-handed body in the mixed sample is in the range of 20% to 30%.

In one embodiment, the right-handed body sample is a mixture of the right-handed body and high-density polyethylene; the left-handed body sample is a mixture of the left-handed body and high-density polyethylene;

The mixture sample is a mixture of the right-handed body, the left-handed body, and high-density polyethylene.

In one embodiment, the diameter of the powder particles of the standard of the right-handed body and the standard of the left-handed body is less than 74 μm.

In one embodiment, the terahertz time domain spectrometer is used to separately test the absorption spectra of the right-handed body sample, the left-handed body sample, the mixed body sample, and the sample to be tested, and respectively obtained right-handed rotation The steps of bulk absorption spectrum, left-handed absorption spectrum, mixed absorption spectrum, and test absorption spectrum include:

Electromagnetic waves in the terahertz band emitted by the terahertz time domain spectrometer are respectively transmitted through the right-handed body sample, the left-handed body sample, the mixed body sample, and the sample to be tested, respectively, to obtain a right-handed transmission spectrum, Left-handed transmission spectrum, mixed transmission spectrum, and tested transmission spectrum;

Analyzing the right-handed transmission spectrum and the reference spectrum to obtain the right-handed absorption spectrum; wherein the reference spectrum is a preset spectrum;

Analyzing the left-handed transmission spectrum and the reference spectrum to obtain the left-handed absorption spectrum;

Analyzing the mixture transmission spectrum and the reference spectrum to obtain an absorption spectrum of the mixture;

The test transmission spectrum and the reference spectrum were analyzed to obtain the test absorption spectrum.

In one embodiment, the step of identifying whether the sample to be tested meets the requirements by the test absorption spectrum according to the right-hand body absorption spectrum, the left-hand body absorption spectrum, and the mixture absorption spectrum includes :

Correspondingly, the characteristic absorption frequency of the right-handed body and the characteristic absorption frequency of the left-handed body are obtained from the right-handed body absorption spectrum, the left-handed body absorption spectrum, the mixed body absorption spectrum spectrum and the test absorption spectrum, respectively. a characteristic absorption frequency of the mixture sample of the right-handed body and the left-handed body and a characteristic absorption frequency of the sample to be tested;

Comparing the characteristic absorption frequency of the sample to be tested with the characteristic absorption frequency of the right-handed body, the characteristic absorption frequency of the sample to be tested, the characteristic absorption frequency of the left-handed body, and the characteristic absorption frequency of the sample to be tested, respectively And determining a composition of the sample to be tested according to a comparison result of the characteristic absorption frequency of the mixed sample, thereby identifying whether the sample to be tested is qualified.

In one embodiment, the relative humidity of the test sample environment in the terahertz time domain spectrometer is no more than 5%.

DRAWINGS

1 is a schematic flow chart of a method for identifying a chiral drug based on a terahertz time domain spectrometer according to an embodiment;

2 is a schematic flow chart of a method for identifying a chiral drug based on a terahertz time domain spectrometer according to another embodiment;

3 is a schematic flow chart of a method for identifying a chiral drug based on a terahertz time domain spectrometer according to still another embodiment;

Figure 4 is a schematic diagram of the terahertz time-domain spectrum of a penicillamine dextrin sample, a penicillamine left-handed sample, and a reference signal;

Figure 5 is a schematic view showing the absorption spectrum of a penicillamine dextrose sample and a penicillamine levorotin sample.

detailed description

The above described objects, features and advantages of the present invention will become more apparent from the aspects of the appended claims.

Electromagnetic radiation in the band of Therahertz (THz, 1THz = 10 ¹² Hz) is electromagnetic radiation between the microwave and the infrared. The electromagnetic wave spectrum of the terahertz band is in the chemical due to the low-frequency rotation and vibrational transition of the molecule. The fields of biomedicine and other fields have broad application prospects. Terahertz Time Domain Spectrometer (THz-TDS) is a spectral detection technology based on femtosecond lasers. It can obtain the absorption information of electromagnetic waves of samples in the terahertz frequency band, and has high signal-to-noise ratio and detection sensitivity. The terahertz time domain spectrometer has a sample holder for the test sample.

Enantiomers of chiral drugs are generally classified into a left-handed body (also named L-form) and a right-handed body (also named as D-form), or an R-form and an S-form. In general, for a pair of enantiomers of a chiral drug, a standard for the left-handed body and the right-handed body can be purchased through a regular channel. In the present embodiment, the chiral drug is exemplified by penicillamine. Penicillamine is a commonly used drug for the treatment of rheumatoid arthritis. However, only the right-handed body (D-enantiomer) is effective. At the same time, the D-enantiomer is also a good therapeutic agent for metabolic diseases and metal poisoning such as lead and mercury. The left-handed body (L-enantiomer) can cause bone marrow damage, olfactory and visual decline, and allergic reactions, etc., with strong toxic and potential carcinogenic effects. At the same time, the cost of D-type penicillamine is higher. D-type penicillamine and L-type penicillamine are difficult to be simple due to general drug testing techniques. That is to say, both the D-type penicillamine and the L-type penicillamine, the test results are shown as penicillamine. Therefore, some lawless elements may use L-type penicillamine instead of D-type penicillamine to earn high profits. Such illegal behavior may cost the patient a great deal of cost, so the identification of D-type penicillamine and L-type penicillamine is very important in practical applications. In this embodiment, both the D-type penicillamine standard and the L-type penicillamine standard are purchased from TCI (Tokyo Chemical Industry referred to as TCI), and their purity is greater than 98%.

1 is a schematic flow chart of a method for identifying a chiral drug based on a terahertz time domain spectrometer according to an embodiment. A method for identifying chiral drugs based on a terahertz time domain spectrometer, comprising:

In step S110, a right-handed body sample, a left-handed body sample, and a mixed body sample of the chiral drug are prepared.

Specifically, the right-handed body contains a right-handed body of a chiral drug, and does not contain a left-handed body. The left-handed sample contains the left-handed body of the chiral drug and does not contain the right-handed body. The mixed body sample contains both a left-handed body and a right-handed body.

In step S130, the absorption spectra of the right-handed body sample, the left-handed body sample, the mixed body sample and the sample to be tested are respectively tested by using a terahertz time-domain spectrometer to obtain a right-handed absorption spectrum, a left-handed absorption spectrum, a mixed absorption spectrum, and The absorption spectrum was tested.

Specifically, as described above, a terahertz time-domain spectrometer can obtain absorption information of an electromagnetic wave of a substance in the terahertz band, that is, an absorption spectrum. The composition of the right-handed body sample, the left-handed body sample, and the mixed-body sample is different, and the absorption spectra of the electromagnetic waves in the terahertz band are also different. In the present embodiment, the absorption spectra of the right-handed body sample, the left-handed body sample, and the mixed-body sample are taken as fingerprint spectra, respectively indicating the absorption spectrum when only the right-handed component is contained in the sample to be tested, and the absorption when only the left-handed body is in the sample to be tested. The absorption spectrum of the spectrum and the sample to be tested have both a left-handed body and a right-handed body. The terahertz time-domain spectrometer is tested on the sample to be tested, and the absorption spectrum of the electromagnetic wave of the sample to be measured in the terahertz band is obtained, that is, the absorption spectrum is tested. The components in the sample to be tested are judged based on the test absorption spectrum and the above fingerprint spectrum.

In step S150, the test absorption spectrum is analyzed according to the right-handed absorption spectrum, the left-handed absorption spectrum, and the mixed absorption spectrum to identify whether the sample to be tested meets the requirements.

Specifically, the test absorption spectrum and the right-handed absorption spectrum are separately analyzed, the absorption spectrum and the left-handed absorption spectrum are tested, and the absorption spectrum and the absorption spectrum of the mixture are tested, and it is concluded that the absorption spectrum of the test absorption spectrum is in agreement with the absorption information of the fingerprint spectrum. Identify whether the sample to be tested contains a right-handed body, or whether it contains a left-handed body, or whether it contains both a right-handed body and a left-handed body. In this way, it can be judged whether the components in the sample to be tested are required or not.

The above method for identifying a chiral drug based on a terahertz time-domain spectrometer firstly prepares a mixture of a right-handed body sample, a left-handed body sample, and a mixture of a right-handed body and a left-handed body, that is, a right-handed body sample, a left-handed body sample, and Mix body samples. Secondly, the absorption spectra of the right-handed sample, the left-handed sample and the mixed body sample were tested by terahertz time-domain spectrometer, and the right-handed absorption spectrum, the left-handed absorption spectrum and the mixed absorption spectrum were obtained. When testing chiral drugs, the absorption spectrum of the sample to be tested is tested by a terahertz time domain spectrometer to obtain a test absorption spectrum. Then, based on the right-handed absorption spectrum, the left-handed absorption spectrum, and the mixed absorption spectrum, the test absorption spectrum is used to identify whether the sample to be tested meets the requirements. Thus, the above method obtains the spectral absorption information of the sample on the terahertz band, and the absorption spectrum of several standard samples of the chiral drug can be used to obtain whether the sample to be tested meets the requirements. Therefore, the above test method is effective and accurate for testing chiral drugs.

2 is a schematic flow chart of a method for identifying a chiral drug based on a terahertz time domain spectrometer of another embodiment. In this embodiment, the right-handed body sample, the left-handed body sample, and the mixed body sample of the chiral drug are prepared, that is, step S110 includes:

In step S111, the standard of the right-handed body and the standard of the left-handed body are respectively dried.

Specifically, the standard of the right-handed body and the standard of the left-handed body were dried in a dry environment of 50-60 ° C for 2 hours. In this way, the moisture in the standard is removed to avoid the absorption of electromagnetic waves by the moisture in the terahertz band, thereby avoiding the interference of moisture on the absorption spectrum of the terahertz time domain spectrometer.

In step S112, the standards of the right-handed body and the standard of the left-handed body are respectively developed into powders.

Specifically, the dried standard of the right-handed body and the standard of the left-handed body are placed in an agate mortar to be sufficiently ground so that the particles of the standard are sufficiently fine. In this way, the absorption spectrum obtained by the test can be made as accurate as possible and the waveform is as good as possible. In the present embodiment, the diameter of the powder particles of the standard of the right-handed body and the standard of the left-handed body is less than 74 μm. The powder particles satisfying the conditions can be sieved out with a corresponding sieve.

In step S113, a preset weight percentage of the right-handed body sample, the left-handed body sample, and the mixed body sample are separately prepared.

Specifically, the right-handed body sample, the left-handed body sample, and the mixed body sample were prepared using the right-handed body standard, the left-handed body standard, and the high-density polyethylene in the step S112. That is, the right-handed body sample is a mixture of a right-handed body and a high-density polyethylene. The left-handed body sample is a mixture of a left-handed body and a high-density polyethylene. The mixed sample is a mixture of a right-handed body, a left-handed body, and a high-density polyethylene. On the one hand, since the high-density polyethylene is easily formed, the right-handed sample, the left-handed sample, and the mixed sample can be easily formed and easily tested. On the other hand, since high-density polyethylene has no absorption of electromagnetic waves in the terahertz band, it is possible to ensure the absorption spectrum of the standard sample of the right-handed body and the right-handed body, and the absorption of the standard of the left-handed body and the left-handed body. The spectra are consistent, and the absorption spectrum of the mixed sample is consistent with the absorption spectrum of the mixture of the dextral standard and the left-handed standard, which can save the standard of the right-handed body and the standard of the left-handed body, thereby saving cost. Further, the weight percentage of the right-handed body in the right-handed body sample is in the range of 20% to 30%; the weight percentage of the left-handed body in the left-handed body sample is in the range of 20% to 30%; in the mixed sample, the left-handed body and The weight percentage of the mixture of the right-handed bodies is in the range of 20% to 30%. In this way, the spectral effect of the measured absorption spectrum is guaranteed to be good.

In this embodiment, the steps of respectively preparing a preset weight percentage of the right-handed body sample, the left-handed body sample, and the mixed body sample are respectively included, that is, after step S113,

In step S114, the right-handed body sample, the left-handed body sample, and the mixed body sample are respectively pressed into a disk-like structure.

Specifically, the above-mentioned right-handed body sample, left-handed body sample, and mixed body sample may be tableted and pressed into a disk-like structure by using a pressure of 30 to 40 MPa. The thickness of the right-handed body sample, the left-handed body sample, and the mixed body sample in this embodiment ranged from 1.5 mm to 2 mm. The diameter of the disc can be 13 mm. Because the sample is too thick, the absorption of electromagnetic waves by the sample in the terahertz band is strong, which may result in a narrow spectral effective frequency range of the detection, and the spectral absorption characteristics of the sample in the high frequency band may be lost. If the thickness of the sample is too small, it is easy to leave interference fringes in the detected spectrogram, which may cause the weaker absorption peak in the absorption spectrum of the sample to be not clearly displayed, affecting the quality of the spectrum. Therefore, the thickness of the disk-shaped sample of the present embodiment can make the absorption spectrum of each sample relatively accurate.

3 is a schematic flow chart of a method for identifying a chiral drug based on a terahertz time domain spectrometer according to still another embodiment. Figure 4 is a schematic representation of the terahertz time-domain spectrum of a penicillamine dextrin sample, a penicillamine left-handed sample, and a reference signal. Figure 5 is a schematic view showing the absorption spectrum of a penicillamine dextrose sample and a penicillamine levorotin sample. The absorption spectra of the right-handed sample, the left-handed sample, the mixed sample and the sample to be tested were respectively measured by a terahertz time-domain spectrometer, and the right-handed absorption spectrum, the left-handed absorption spectrum, the mixed absorption spectrum, and the tested absorption spectrum were respectively obtained. The step, step S130, includes:

Step S131, the electromagnetic waves in the terahertz frequency band emitted by the terahertz time domain spectrometer are respectively transmitted to the right-handed body sample, the left-handed body sample, the mixed body sample, and the sample to be tested, respectively, to obtain a right-handed transmission spectrum, a left-handed transmission spectrum, and a mixture. Transmission spectroscopy and test transmission spectroscopy.

Specifically, the right-handed sample, the left-handed sample, the mixed sample, and the sample to be tested can be respectively placed on a sample holder of a terahertz time-domain spectrometer, so that the electromagnetic wave in the terahertz band transmits the right-handed sample and the left-handed sample. The mixture sample and the sample to be tested respectively obtain a right-handed transmission spectrum, a left-handed transmission spectrum, a mixture transmission spectrum, and a test transmission spectrum. Specifically, the relative humidity of the test sample environment in the terahertz time domain spectrometer is not more than 5%. The relative humidity of the sample holder can be ensured by filling the sample holder with nitrogen. In this embodiment, the terahertz time-domain spectroscopy system is a THz-4000 terahertz time-domain spectroscopy system produced by Teraview, and the terahertz spectral width is 0.06 to 4.0 THz. During the scanning process of the signal, the scanning range is 0- At 1200 ps, the acquisition rate is 30 scans/second and the spectral resolution is 1.2 cm ^-1 .

In step S132, the right-handed transmission spectrum and the reference spectrum are analyzed to obtain a right-handed absorption spectrum.

In step S133, the left-handed transmission spectrum and the reference spectrum are analyzed to obtain a left-handed absorption spectrum.

In step S134, the mixture transmission spectrum and the reference spectrum are analyzed to obtain a mixture absorption spectrum.

In step S135, the test transmission spectrum and the reference spectrum are analyzed to obtain a test absorption spectrum.

Specifically, the reference spectrum is a preset spectrum. In this embodiment, in the terahertz time domain spectrometer, the spectrum obtained when the sample rack is idling is the reference spectrum. Thus, by analyzing the right-handed transmission spectrum and the reference spectrum, a right-handed absorption spectrum can be obtained. Similarly, a left-handed absorption spectrum, a mixture absorption spectrum, and a test absorption spectrum are obtained. The following is a detailed description of the post-processing of the terahertz time-domain spectrometer for the reference signal (reference spectrum) and the sample signal (right-handed transmission spectrum, left-handed transmission spectrum, mixed transmission spectrum or test transmission spectrum):

Let the time domain waveform of the reference signal be Er(t), and the time domain waveform of the sample signal be Es(t), and perform Fourier transform on Er(t) and Es(t) respectively to obtain the frequency domain distribution of the two signals. Er(ω) and Es(ω):

Er(ω)=Ar(ω)exp[-iφr(ω)]=∫Er(t)exp(-iωt)dt (1)

Es(ω)=As(ω)exp[-iφs(ω)]=∫Es(t)exp(-iωt)dt (2)

In equations (1) and (2), Ar(ω) and As(ω) are the amplitudes of the electric field of the reference signal and the sample signal, respectively; φr(ω) and iφs(ω) are the phases of the reference signal and the electric field of the sample signal, respectively. ;i is an imaginary unit. The terahertz time-domain spectra of penicillamine dextral sample 410, penicillamine left-handed sample 420, and reference signal 430 are shown in FIG. As can be seen from FIG. 4, the light intensity of the penicillamine dextrose sample 410 and the light intensity of the penicillamine left-handed body 420 are relatively small relative to the reference signal 430.

Based on equations (1) and (2), a refractive index n(ω) and an absorption coefficient α(ω) of the sample are calculated using a data processing model based on the Fresnel formula:

In the above formula, ρ(ω) and φ(ω) are the amplitude ratio and phase difference of the sample signal and the reference signal, respectively, d is the thickness of the sample; c is the propagation speed of the electromagnetic wave in vacuum.

It should be noted that the order of the above steps S132 to S135 is not limited thereto, as long as the absorption spectrum of each sample can be obtained.

In this embodiment, according to the right-handed absorption spectrum, the left-handed absorption spectrum, and the mixed absorption spectrum, the test absorption spectrum is used to identify whether the sample to be tested meets the requirements, that is, step S150 includes:

Step S151, obtaining the characteristic absorption frequency of the right-handed body, the characteristic absorption frequency of the left-handed body, the right-handed body and the left-handed body from the right-handed absorption spectrum, the left-handed absorption spectrum, the mixed absorption spectrum and the test absorption spectrum, respectively. The characteristic absorption frequency of the mixed sample and the characteristic absorption frequency of the sample to be tested.

Step S152, respectively comparing the characteristic absorption frequency of the sample to be tested with the characteristic absorption frequency of the right-handed body, the characteristic absorption frequency of the sample to be tested and the characteristic absorption frequency of the left-handed body, the characteristic absorption frequency of the sample to be tested, and the characteristic absorption of the mixed sample. The frequency, based on the comparison result, determines the composition of the sample to be tested, thereby identifying whether the sample to be tested is qualified.

Specifically, as described above, a chiral drug such as penicillamine. In general, for solids that do not contain heavy atoms, the absorption in the far-infrared region of the terahertz band is mainly intermolecular vibration, including 1) intermolecular interactions such as hydrogen bond vibration, etc.; 2) lattice vibration, That is, the molecules or ions inside the crystal as a whole, their vibration absorption caused by the relative motion (translation, twist, or swing) in the crystal lattice. The right-handed absorption spectrum 510 and the left-handed absorption spectrum 520 of penicillamine obtained by a terahertz time domain spectrometer are shown in FIG. The terahertz characteristic absorption peak frequency of the penicillamine corresponding isomer can be obtained from Fig. 5.

The penicillamine enantiomers each have a strong absorption peak in the 1.93 THz band. The related literature indicates that the crystal structure of the corresponding isomer of penicillamine is orthogonal, the unit cell contains four single molecules, and the space group is P2221. The difference in crystal structure makes them have significant spectra in the terahertz band. difference. In addition, since D- and L-penicillamine are enantiomers, their molecular structures are the same and the configurations are mirror images of each other. This difference in configuration results in a certain difference in intramolecular and intermolecular interactions, ie, differences in lattice vibration. From the experimental measurements, their absorption spectra have a certain difference in the peak position of a strong absorption peak, and there are 2-3 weak absorption peak differences in other low frequency or high frequency bands. The penicillamine enantiomers can be identified using these differences in absorption peaks and are accurately identified.

Table 1 shows the terahertz characteristic absorption peak frequencies of the penicillamine enantiomers.

Table 1 Penicillamine isomer terahertz characteristic absorption frequency

In addition, the absorption spectrum of the mixed penicillamine has six characteristic absorption frequencies of 1.51 THz, 1.57 THz, 1.93 THz, 2.08 THz, 2.34 THz, and 2.49 THz, respectively.

Therefore, comparing the characteristic absorption frequency of the sample to be tested and the characteristic absorption frequency of the mixed sample, if the characteristic absorption frequency of the sample to be tested is also consistent with the absorption frequency of the above six characteristics, the sample to be tested is penicillamine left-handed body and Penicillium A mixture of amine dextrose. Similarly, it can be identified whether the sample to be tested is penicillamine or a penicillamine right-handed body. Thereby, it is possible to identify whether the sample to be tested is acceptable. If the identification result indicates that the sample to be tested and the component that meets the requirements, the sample to be tested is qualified, otherwise it is unqualified.

The technical features of the above-described embodiments may be arbitrarily combined. For the sake of brevity of description, all possible combinations of the technical features in the above embodiments are not described. However, as long as there is no contradiction between the combinations of these technical features, All should be considered as the scope of this manual.

The above-described embodiments are merely illustrative of several embodiments of the present invention, and the description thereof is more specific and detailed, but is not to be construed as limiting the scope of the invention. It should be noted that a number of variations and modifications may be made by those skilled in the art without departing from the spirit and scope of the invention. Therefore, the scope of the invention should be determined by the appended claims.

Claims (10)

1. A method for identifying chiral drugs based on a terahertz time domain spectrometer, characterized in that it comprises:

   Preparing a right-handed body sample, a left-handed body sample, and a mixed body sample of the chiral drug; wherein the mixed body sample contains a left-handed body and a right-handed body of the chiral drug;

   Measuring, by the terahertz time domain spectrometer, absorption spectra of the right-handed body sample, the left-handed body sample, the mixed body sample, and the sample to be tested, respectively, to obtain a right-handed absorption spectrum, a left-handed absorption spectrum, Mixed absorption spectrum, test absorption spectrum;

   The test absorption spectrum is analyzed according to the right-handed absorption spectrum, the left-handed absorption spectrum, and the mixture absorption spectrum to identify whether the sample to be tested meets the requirements.
2. The method according to claim 1, wherein said step of preparing a right-handed sample, a left-handed body sample, and a mixed body sample of said chiral drug comprises:

   Drying the standard of the right-handed body of the chiral drug and the standard of the left-handed body;

   The standard of the right-handed body and the standard of the left-handed body are respectively developed into a powder form;

   A preset weight percentage of the right-handed body sample, the left-handed body sample, and the mixed body sample are separately prepared.
3. The method according to claim 2, wherein the step of separately preparing the preset weight percentage of the right-handed body sample, the left-handed body sample, and the mixed-body sample further comprises:

   The right-handed body sample, the left-handed body sample, and the mixed body sample were respectively pressed into a disk-like structure.
4. The method according to claim 3, wherein the thickness of the right-handed body sample, the left-handed body sample, and the mixed body sample are all in the range of 1.5 mm to 2 mm.
5. The method according to claim 2, wherein the weight percentage of the right-handed body in the right-handed body sample is in the range of 20% to 30%; the weight of the left-handed body in the left-handed body sample The percentage is in the range of 20% to 30%;

   The weight percentage of the mixture of the left-handed body and the right-handed body in the mixed sample is in the range of 20% to 30%.
6. The method according to claim 2, wherein said right-handed body sample is a mixture of said right-handed body and high-density polyethylene; said left-handed body sample is a mixture of said left-handed body and high-density polyethylene ;as well as

   The mixture sample is a mixture of the right-handed body, the left-handed body, and high-density polyethylene.
7. The method according to claim 2, wherein the diameter of the powder particles of the standard of the right-handed body and the standard of the left-handed body is less than 74 μm.
8. The method according to claim 1, wherein said detecting a absorption spectrum of said right-handed body sample, said left-handed body sample, said mixed body sample, and said sample to be tested by said terahertz time domain spectrometer And obtaining the right-handed absorption spectrum, the left-handed absorption spectrum, the mixed absorption spectrum, and the test absorption spectrum, respectively, comprising:

   Electromagnetic waves in the terahertz band emitted by the terahertz time domain spectrometer are respectively transmitted through the right-handed body sample, the left-handed body sample, the mixed body sample, and the sample to be tested, respectively, to obtain a right-handed transmission spectrum, Left-handed transmission spectrum, mixed transmission spectrum, and tested transmission spectrum;

   Analyzing the right-handed transmission spectrum and the reference spectrum to obtain the right-handed absorption spectrum; wherein the reference spectrum is a preset spectrum;

   Analyzing the left-handed transmission spectrum and the reference spectrum to obtain the left-handed absorption spectrum;

   Analyzing the mixture transmission spectrum and the reference spectrum to obtain an absorption spectrum of the mixture;

   The test transmission spectrum and the reference spectrum were analyzed to obtain the test absorption spectrum.
9. The method according to claim 1, wherein said sample to be tested is identified from said test absorption spectrum based on said right-handed absorption spectrum, said left-handed absorption spectrum, and said mixture absorption spectrum The steps to meet the requirements include:

   Correspondingly, the characteristic absorption frequency of the right-handed body and the characteristic absorption frequency of the left-handed body are obtained from the right-handed body absorption spectrum, the left-handed body absorption spectrum, the mixed body absorption spectrum spectrum and the test absorption spectrum, respectively. a characteristic absorption frequency of the mixture sample of the right-handed body and the left-handed body and a characteristic absorption frequency of the sample to be tested;

   Comparing the characteristic absorption frequency of the sample to be tested with the characteristic absorption frequency of the right-handed body, the characteristic absorption frequency of the sample to be tested, the characteristic absorption frequency of the left-handed body, and the characteristic absorption frequency of the sample to be tested, respectively And determining a composition of the sample to be tested according to a comparison result of the characteristic absorption frequency of the mixed sample, thereby identifying whether the sample to be tested is qualified.
10. The method of claim 1 wherein the relative humidity of the test sample environment in the terahertz time domain spectrometer is no more than 5%.

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