X-ray optics; polycapillary X-ray lens; confocal micro X-ray fluorescence; medicine with capsule; non-destructive and in-situ analysis

The confocal micro X-ray fluorescence technology based on two polycapillary X-ray lenses is used to analyze the elements in the medicines with capsule non-destructively. In this technology, two confocal lenses form confocal volume, and only the X-rays from the confocal volume can be detected by the detector, which ensures non-destructive and in-situ analysis of elements in the capsule shell and the medicine inside to identify their species. X-ray fluorescence spectral characteristics of four types of medicines with capsule are analyzed. The experimental results show that different medicines have different X-ray fluorescence spectra, and different spectra correspond to different elemental compositions, which could be used to identify medicines. The confocal micro X-ray fluorescence technology can be used in the non-destructive and in-situ analysis of the samples with capsule, and has potential applications in identifying the types and the authenticity of medicines with capsule.

Drugs are closely related to human life and health. Drug safety detection and identification technology is an important means to carry out drug safety monitoring, strengthen drug safety management and conduct market supervision. It plays an important role in maintaining drug safety and protecting human life and health. With the advancement of science and technology, the detection and identification technology of drug safety has developed from simple morphology and visual colorimetric identification to atomic absorption, gas chromatography, liquid chromatography, fluorescence spectrophotometer, ultraviolet spectrophotometer, mass spectrometry, infrared, capillary electrophoresis modern analytical techniques such as instrumentation and molecular biology.

In recent years, fingerprint technology has become one of the effective means to detect and identify the quality of medicines. This technology refers to the use of certain analytical methods (such as spectrum or chromatography) after the sample is properly processed to obtain a spectrum or image that can indicate the characteristics of the sample. At present, the fingerprint technology has involved many methods: thin layer chromatography, high performance liquid chromatography, gas chromatography, high performance capillary electrophoresis, ultraviolet spectroscopy, infrared spectroscopy, mass spectrometry, nuclear magnetic resonance, X-ray diffraction and X-ray fluorescence.

Capsule drugs are commonly used drugs. How to conduct non-destructive in-situ rapid detection of drugs contained in capsules without destroying the capsule shell is a problem that researchers are more concerned about and a technical challenge. Many of the above analysis techniques are destructive analysis, and the pretreatment process of the sample before analysis is complicated, so these destructive analysis techniques cannot perform non-destructive in situ on the drugs contained in the capsule without destroying the capsule shell. Quickly detected.

It is well known that among the above techniques, ordinary X-ray fluorescence and X-ray diffraction can perform non-destructive analysis of samples, but the capsule shell will be affected when analyzing the medicine inside the capsule without destroying the capsule. In this paper, a confocal microbeam X-ray fluorescence spectrometer based on two capillary X-ray lenses is proposed to analyze capsule drugs.

Compared with previous methods, the confocal microbeam X-ray fluorescence technique used in this paper can perform non-destructive in situ detection of medicines inside capsules without destroying the capsules.

The polycapillary X-ray lens used to build the confocal microbeam X-ray fluorescence spectrometer is an optical device made by the principle of X-ray total reflection. Generally, it is composed of 2×10⁵ ~ 6×10⁵ with an aperture size of several microns. It is composed of glass capillary tube, and the lens has the function of converging X-rays, which improves the luminous flux irradiated on the sample, thereby shortening the measurement time; the two capillary X-ray lenses are in confocal state, which enables non-destructive three-dimensional analysis of the sample using this technique. Capsule drugs are composed of two parts. The outer layer is a relatively thin capsule shell, and the capsule is wrapped with drugs for treating diseases. Through the confocal microbeam X-ray fluorescence spectrometer, the capsule shell can be tested without destroying the capsule drugs. And the drugs wrapped in the capsules are tested in situ.

If any capsule drugs are unqualified, it can be determined whether it is caused by the capsule shell or the drugs contained in the capsule, and then the source of the unqualified parts can be traced separately. In this paper, the characteristics of capsule medicines were analyzed by using polycapillary X-ray lens confocal microbeam X-ray fluorescence technology, and the characteristics of X-ray fluorescence spectra corresponding to several medicines were analyzed.

A confocal microbeam X-ray fluorescence spectrometer consists of a polycapillary X-ray converging lens and a polycapillary X-ray collimating beam lens (Figure 1).

Fig.1 Confocal micro X-ray fluorescence spectrometer

The principle of the spectrometer is as follows: the polycapillary X-ray converging lens condenses the X-rays emitted by the ordinary laboratory X-ray source into a relatively small exit focal spot, and a parallel beam lens is placed in front of the detector. By adjusting the polycapillary X-ray parallel beam lens, the entrance focal spot of the polycapillary X-ray collimating beam lens and the exit focal spot of the polycapillary X-ray converging lens coincide to form a confocal micro-element, at this time, the detector can only detect the X-rays from the confocal micro-element Signal. The capillary X-ray lens confocal micro-beam X-ray fluorescence technology is different from the micro-beam X-ray fluorescence technology based only on the polycapillary X-ray converging lens. It can move the sample through the debugging frame, so that the confocal micro-element moves in the sample, thereby It can realize point-to-point three-dimensional non-destructive analysis of samples.

In this fluorescence spectrometer, the light source used is an ordinary laboratory X-ray molybdenum target light source, and the detector is a silicon drift detector with a resolution of about 192 eV at 5.9 keV. The length of the polycapillary X-ray converging lens is 39.6mm, and the length of the polycapillary X-ray collimating beam lens is 11.8mm; at 17.4keV, the polycapillary X-ray converging lens has an entrance focal length of 46mm and an exit focal length of 15.6mm. The magnification is 1750, the entrance focal length of the polycapillary X light condensing lens is 10.7mm, and the sizes of the confocal microelements in the X, Y and Z directions (Fig. 1) are 49.2, 47.6, and 32.2 μm, respectively. When using this spectrometer to detect capsules, the voltage and current used are 30kV and 500μA, respectively, and each detection time is 40s.

As shown in Table 1, the minimum detection limit m_MDL of the confocal microbeam X-ray fluorescence spectrometer was measured using a thin film sample (Micromatter), and the minimum detection limit was

where
m_a is the mass of element a in the confocal microelement,
N_{a, B} are the background counts corresponding to the characteristic peaks of element a, and
N_{a, N} are the pure peak counts of the characteristic peaks of element a.

Table 1 Detection limits of confocal micro X-ray fluorescence spectrometer（35 kV，600 μA）

In this paper, four kinds of capsule medicines were analyzed, which were denoted as A, B, C, and D respectively. Figure 2 is a physical image of one of the capsule medicines being directly fixed on the sample stage for analysis.

Fig. 2 Picture of testing medicine with capsule

Figure 3 is a screenshot of the computer interface for determining the position of the scanning point.

Fig. 3 Picture of marking medicine with capsule

The intersection of the “十” cross-wire in the interface points to the position of the confocal micro-element of the confocal spectrometer. After fixing the sample to the sample stage, move the sample stage to make the “十” The intersection of the cross wire indicates the sample to be tested, and then the three-dimensional scanning analysis of the sample can be performed by controlling the movement of the sample stage.

Fig. 4 X-ray fluorescence spectrum of capsule shell

Fig. 4 is the corresponding X-ray fluorescence spectrum of the confocal micro-element in the capsule shell, Fig. 5 is the corresponding X-ray fluorescence spectrum of the confocal micro-element irradiated to the capsule shell and its internal medicine at the same time, Fig. 6 is the confocal micro-element transparent Enter the corresponding fluorescence spectrum of the drug through the capsule shell. Figure 4 only contains Ti, Figure 5 contains Ti, Fe, Ca and K fluorescence peaks, and Figure 6 contains Fe, Ca and K fluorescence peaks. The number of element species contained in the capsule drug shown in Figure 5 is exactly equal to the sum of the element species contained in the capsule shell and its internal drug in Figure 4 and Figure 6.

Fig. 5 X-ray fluorescence spectrum of medicinal powder and capsule shell

Fig. 6 X-ray fluorescence spectrum of medicinal powder A

From these three spectra, it can be seen that with the confocal microelement Going deeper into the capsule, the Ti fluorescence peak disappears on the spectrum, and the Fe, Ca and K fluorescence peaks appear. This is because the confocal microelements completely enter the drug in the capsule through the capsule shell, and the drug does not contain Ti , and contains Fe, Ca and K, so it can be known from Figures 4 to 6 that the capsule shell of this capsule medicine contains Ti, and the medicine in the capsule contains Fe, Ca and K.

It can be seen from the above-mentioned in-depth scanning analysis process of the drug that the capillary X-ray lens confocal microbeam X-ray fluorescence technology can be used，in the case of not destroying the capsule shell, the non-destructive in-situ analysis of the capsule shell and the drug inside the capsule was carried out respectively.

Figures 6 to 9 are spectra obtained by X-ray fluorescence detection of drugs contained in different types of capsule drugs A, B, C, and D with a confocal microbeam X-ray fluorescence spectrometer. It can be seen that the types of elements contained in the medicines in different capsule medicines are not exactly the same, so the type of medicines can be identified by the X-ray fluorescence spectrum corresponding to the medicines.

Fig. 7 X-ray fluorescence spectrum of medicinal powder B

Fig. 8 X-ray fluorescence spectrum of medicinal powder C

Fig. 9 X-ray fluorescence spectrum of medicinal powder D

In the capillary X-ray lens confocal microbeam X-ray fluorescence technology, the two lenses are in a confocal state to form a confocal microelement, which ensures that the detector can only detect the X-ray signal from the confocal microelement. The confocal microbeam X-ray fluorescence technique can be used for non-destructive in situ analysis of the capsule shell and the drug inside the capsule drug without destroying the capsule shell. This technology has potential application value in the identification of drug species.