阅读说明：本技术 一种碳酸镧或其制剂中碱式碳酸镧杂质的检定方法 (Method for detecting lanthanum carbonate or lanthanum hydroxycarbonate impurity in preparation thereof ) 是由 安明 常珍 况斌 祝江业 张婵娟 杨清燕 于 2018-06-08 设计创作，主要内容包括：本发明提供了一种在固态下检定碳酸镧原料或其制剂中碱式碳酸镧杂质的方法。将碳酸镧或其制剂充分研细后,加入不同量的碱式碳酸镧,再将该混合物与刚玉按一定比例充分混合均匀,制备系列标准曲线样品,用粉末X-射线衍射法对各标准曲线样品进行扫描,绘制标准曲线,得到线性方程。将待测碳酸镧或其制剂与刚玉按一定比例充分混合均匀,制备成供试品,同法测定,通过将供试品中碱式碳酸镧与刚玉特征峰衍射强度的比值代入线性方程中,从而计算出样品中碱式碳酸镧的含量。本发明的方法可用于分析检测碳酸镧或碳酸镧制剂中的碱式碳酸镧杂质,该方法操作简便、线性范围宽、线性关系良好、精密度好、准确性高、耐用性好、检测灵敏度高。(The invention provides a method for detecting alkali lanthanum carbonate impurities in a lanthanum carbonate raw material or a preparation thereof in a solid state. Fully grinding lanthanum carbonate or a preparation thereof, adding different amounts of lanthanum carbonate hydroxide, fully and uniformly mixing the mixture and corundum according to a certain proportion to prepare a series of standard curve samples, scanning each standard curve sample by using a powder X-ray diffraction method, and drawing a standard curve to obtain a linear equation. And (2) fully and uniformly mixing the lanthanum carbonate or the preparation thereof to be detected and corundum according to a certain proportion to prepare a test sample, and substituting the ratio of the diffraction intensity of the characteristic peak of the lanthanum carbonate hydroxide and the corundum in the test sample into a linear equation to calculate the content of the lanthanum carbonate hydroxide in the sample. The method can be used for analyzing and detecting the lanthanum carbonate or the lanthanum carbonate hydroxide impurity in the lanthanum carbonate preparation, and has the advantages of simple and convenient operation, wide linear range, good linear relation, good precision, high accuracy, good durability and high detection sensitivity.)

1. A method for detecting the content of alkali lanthanum carbonate in a lanthanum carbonate raw material or a lanthanum carbonate preparation comprises the following steps:

a. Preparation of standard curve sample: weighing a proper amount of lanthanum carbonate raw material or lanthanum carbonate preparation sample fine powder, respectively and quantitatively adding different amounts of lanthanum carbonate hydroxide, then adding corundum into each mixture according to a certain mass ratio, and fully and uniformly mixing to prepare a series of standard curve samples;

b. Respectively scanning the standard curve samples prepared in the step a by using an X-ray diffractometer;

c. Quantitative determination: respectively reading out the diffraction intensities of the alkali lanthanum carbonate and corundum characteristics in PXRD diffraction patterns of each standard curve sample, drawing a standard curve by taking the ratio of the diffraction intensities of the alkali lanthanum carbonate and corundum characteristics as a vertical coordinate and the ratio of the mass of the alkali lanthanum carbonate and corundum in the sample as a horizontal coordinate to obtain a linear equation;

d. Preparation of a sample to be tested: fully grinding lanthanum carbonate to be detected or a lanthanum carbonate preparation to be detected, quantitatively adding corundum according to a certain proportion, and fully and uniformly mixing to prepare a sample to be detected;

e. D, scanning the sample to be detected prepared in the step d by using an X-ray diffractometer;

f. Calculating the content of the sample to be detected: respectively reading the diffraction intensities of the characteristic diffraction peaks of the alkali lanthanum carbonate and the corundum in the PXRD diffraction pattern of the sample, calculating the ratio of the diffraction intensities to the characteristic diffraction peaks of the alkali lanthanum carbonate and the corundum, and substituting the ratio into the linear equation obtained in the step d, so that the mass ratio of the alkali lanthanum carbonate to the corundum can be calculated; and then, the mass of the lanthanum carbonate hydroxide is calculated according to the mass of the corundum, and the content of the lanthanum carbonate hydroxide to be detected or the lanthanum carbonate hydroxide in the lanthanum carbonate preparation to be detected is further calculated.

2. The assay method according to claim 1, wherein said sample of lanthanum carbonate or lanthanum carbonate formulation in step a is a sample that is free of lanthanum hydroxycarbonate.

3. the assay of claim 1, wherein the lanthanum hydroxycarbonate is a potential degradation impurity of a lanthanum carbonate feedstock or lanthanum carbonate formulation having the formula La (CO)₃)OH。

4. An assay method according to claim 3, wherein said lanthanum hydroxycarbonate is selected from at least one lanthanum hydroxycarbonate polymorph.

5. The assay method according to claim 4, wherein said lanthanum hydroxycarbonate is selected from the group consisting of lanthanum hydroxycarbonate form I and lanthanum hydroxycarbonate form II.

6. The assay method according to claim 1, wherein in step a, at least 5 parts of the fine powder are weighed.

7. The assay method according to any one of claims 6, wherein in step a, the fine powder is weighed in an amount of 6 parts.

8. the assay method according to claim 1, wherein in step a, a proper amount of the fine powder is weighed and a plurality of parts of the fine powder are weighed, and lanthanum carbonate hydroxide with different amounts is quantitatively added, so that each lanthanum carbonate hydroxide crystal form accounts for 0.10-10.00% of the weight of lanthanum carbonate.

9. The assay method according to claim 8, wherein in step a, when the fine powder is weighed as a raw lanthanum carbonate material, different amounts of lanthanum carbonate hydroxide are respectively added in a quantitative manner, so that each lanthanum carbonate hydroxide crystal form accounts for 0.10% to 3.00% of the weight of lanthanum carbonate.

10. An assay method as claimed in claim 9, wherein in step a, each of the lanthanum hydroxycarbonate forms comprises lanthanum carbonate in the following weight proportions:

the mass fractions of the basic californium carbonate I are respectively 2.7 percent, 1.8 percent, 1.44 percent, 0.9 percent, 0.36 percent and 0.18 percent,

the mass fractions of the lanthanum hydroxycarbonate II are respectively 3.0%, 2.0%, 1.6%, 1.0%, 0.4% and 0.2%.

11. The assay method of claim 1 wherein in step a, when the fine powder is californium carbonate, the lanthanum hydroxycarbonate is dosed separately in different amounts so that each form of lanthanum hydroxycarbonate is in the range of 0.50% to 10.00% by weight of californium carbonate.

12. An assay method as claimed in claim 11, wherein in step a, each of the lanthanum hydroxycarbonate forms comprises lanthanum carbonate in the following weight proportions:

The mass fractions of the basic lanthanum carbonate I are respectively 8.16%, 6.8%, 5.44%, 3.4%, 1.36% and 0.68%,

The mass fractions of the lanthanum hydroxycarbonate II are respectively 7.12%, 7.6%, 6.08%, 3.8%, 1.52% and 0.76%.

13. An assay method according to claim 1, wherein said corundum is selected from the group consisting of alpha Al₂O₃。

14. The assay method as claimed in claim 1, wherein, in the step a, when the fine powder to be weighed is a raw lanthanum carbonate, the mixed powder of the raw lanthanum carbonate, lanthanum carbonate hydroxide I and/or lanthanum carbonate hydroxide II and corundum (alpha-Al)₂O₃) The mass ratio is 5-1: 1, preferably 2: 1.

15. The assay method as claimed in claim 1, wherein in the step a, when the fine powder to be weighed is a lanthanum carbonate raw material, the lanthanum carbonate preparation fine powder isMixing powder with lanthanum carbonate hydroxide I and/or lanthanum carbonate hydroxide II and corundum (alpha-Al)₂O₃) The mass ratio is 10-1: 1, preferably 5: 1.

16. The assay method as claimed in claim 1, wherein in the step a, the sample fine powder of lanthanum carbonate or lanthanum carbonate preparation is fully ground in advance to obtain the sample fine powder of lanthanum carbonate or lanthanum carbonate preparation.

17. The assay method according to claim 1, wherein in steps b and e, the 2 θ range of the scanning using the X-ray diffractometer is 3 to 50 °, preferably 9 to 40 °.

18. The assay method of claim 1 wherein, when assaying for lanthanum hydroxycarbonate impurities in californium carbonate starting material, lanthanum hydroxycarbonate I exhibits a characteristic 17.6 ° diffraction peak, lanthanum hydroxycarbonate II exhibits a characteristic 20.3 ° diffraction peak and corundum exhibits a characteristic 35.0 ° diffraction peak.

19. The assay method of claim 1 wherein lanthanum carbonate hydroxide I has a characteristic diffraction peak of 17.6 °, lanthanum carbonate hydroxide II has a characteristic diffraction peak of 26.0 ° and corundum has a characteristic diffraction peak of 35.0 ° when assaying californium basic carbonate impurities in a lanthanum carbonate formulation.

20. The assay method according to claim 1,

the linear equation for the preferred standard curve in step c is as follows:

y is ax + b, wherein

y is I_j/I_SteelNamely the diffraction intensity ratio of the characteristic peaks of alkali lanthanum carbonate I and/or alkali lanthanum carbonate II and corundum in PXRD spectrogram,

x is m_j/m_SteelI.e. the ratio of lanthanum carbonate I and/or lanthanum hydroxycarbonate II in the mixture to the mass of corundum,

The slope a isNamely, the diffraction reference intensity of the alkali lanthanum carbonates I and (or) II in PXRD spectrogram and the characteristic peak relative to corundum.

21. the assay method of claim 1, wherein said lanthanum carbonate preparation comprises lanthanum carbonate chewable tablets, lanthanum carbonate particles, californium carbonate dry suspension, lanthanum carbonate capsules, lanthanum carbonate dispersible tablets.

22. an assay method according to claim 1, wherein the measurement conditions during scanning by the X-ray diffractometer are: the Cu Kalpha target is adopted, the tube pressure and the tube flow are respectively 40KV and 100mA, the divergence slit and the anti-divergence slit are 1 degree, the receiving slit is 0.30mm, the detector is a sodium iodide scintillation counter, theta-2 theta linkage continuous scanning is carried out, and the scanning speed is 2 degrees per minute (0.02 degrees step width).

Technical Field

The invention belongs to the field of analytical chemistry, and particularly relates to a method for analyzing and detecting impurities in lanthanum carbonate hydroxide by using a powder X-ray diffraction (PXRD) method, and more particularly relates to a method for analyzing and detecting impurities in lanthanum carbonate or lanthanum carbonate hydroxide in a preparation thereof.

Technical Field

Hyperphosphatemia is a common complication in Chronic Kidney Disease (CKD), especially end-stage kidney disease (ESRD), and is seen in 80% of dialysis patients. Current treatment for hyperphosphatemia is mainly limited in phosphorus intake, extensive dialysis, use of phosphorus binders and, if necessary, parathyroidectomy plus autografting.

The traditional phosphorus binding agent is mainly an aluminum-containing calcium-containing phosphorus binding agent, and the traditional aluminum salt of the phosphorus binding agent can cause toxic and side effects of resisting aluminum accumulation such as erythropoiesis-stimulating hormone anemia, aluminum-related osteodystrophy, central nervous system damage and the like; calcium salts increase the risk of hypercalcemia, which can lead to calcification of soft tissues such as the cardiovascular system and low-turnover bone disease, resulting in accelerated renal dysfunction.

Lanthanum carbonate (Fosrenol) was developed by charle (shire) of england as a novel non-aluminum, non-calcium phosphorus binder for the treatment of hyperphosphatemia in chronic renal failure patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis. It is now marketed in more than 20 countries throughout the world, including the united states, uk, france, germany, japan, canada, switzerland, etc. The Chinese approved imported lanthanum carbonate chewable tablets (trade name: Foster) of summer corporation in 2/10/2012. Lanthanum trivalent cation has strong affinity with phosphorus, lanthanum carbonate releases trivalent lanthanum ion after entering the digestive tract through oral administration, and the trivalent lanthanum ion is combined with the phosphorus to form insoluble lanthanum salt which is not easy to be absorbed by the digestive tract, and lanthanum does not influence the absorption of fat-soluble vitamins. Lanthanum carbonate is hardly absorbed in the gastrointestinal tract and accumulates in the tissues of the body. Lanthanum carbonate is currently the best selective new drug for the treatment of hyperphosphatemia in renal disease.

the molecular formula of lanthanum carbonate is La₂(CO₃)₃·XH₂O (X represents 4-5 mol), and the molecular weight of the anhydride is 457.8.

In order to ensure the safety of medication, the research on potential degradation impurities in the medicine is required in the current new medicine development guiding principles of various countries and international organizations. Lanthanum carbonate under damp heat conditionThen impurities of alkali lanthanum carbonate I and alkali lanthanum carbonate II are formed by decarboxylation, and the molecular formulas are La (CO)₃) OH, their binding to phosphorus is different, so the therapeutic effect is also different. The existing technologies for researching drug impurities (including chromatographic technology and spectroscopic technology) basically require that a drug and impurities thereof are dissolved in a proper solvent, lanthanum carbonate and lanthanum carbonate hydroxide for degrading the impurities thereof are not dissolved in various solvents except acid, lanthanum carbonate and lanthanum carbonate hydroxide in an acid solvent are dissociated into lanthanum ions, and the lanthanum carbonate hydroxide as impurities thereof cannot be distinguished.

The patent (CN101484798) applied by xiaer international licensing limited company adopts powder X-ray diffraction method to detect lanthanum carbonate hydroxide by Rietveld refining full spectrum fitting method, but the precondition of Rietveld refining is that the crystal structure parameters of each phase must be known, and the patent does not disclose the crystal structure parameters of each phase, so the invention can not be implemented by the skilled person through the patent, and the patent application is regarded as withdrawn, and the patent application does not really solve the quantitative analysis and detection of the lanthanum carbonate impurity in the lanthanum carbonate raw material or the preparation thereof. In addition, Rietveld refinement is time-consuming and tedious, and the impurity content of lanthanum carbonate or the lanthanum hydroxycarbonate in the preparation thereof cannot be detected quickly and simply. In addition to this patent application and its foreign family patents, there is no other method for detecting and analyzing lanthanum carbonate impurities in lanthanum carbonate raw materials and preparations so far. With the increasingly deep research and development work of lanthanum carbonate and preparations thereof, in order to ensure the drug safety of the products to the public after the products are finally marketed, a simple, convenient, rapid and accurate detection method for detecting lanthanum carbonate raw materials and lanthanum carbonate basic impurities in the preparations thereof is urgently needed to be developed.

Disclosure of Invention

The invention aims to solve the technical problem that the conventional technology cannot analyze and detect lanthanum carbonate or lanthanum hydroxycarbonate degrading impurities in a preparation thereof, and provides a method for detecting the impurity content of lanthanum carbonate or lanthanum hydroxycarbonate in the preparation thereof in a solid state.

the technical scheme provided by the invention is as follows: the method adopts a powder X-ray diffraction technology, and adopts an internal standard quantitative analysis method to quickly, accurately and simply detect the content of lanthanum carbonate impurities in the solid state or the preparation of the lanthanum carbonate impurities. Methods for assaying lanthanum carbonate or lanthanum hydroxycarbonate impurities in formulations thereof include, but are not limited to, lanthanum hydroxycarbonate I and lanthanum hydroxycarbonate II.

The invention provides a method for detecting the content of alkali lanthanum carbonate in a lanthanum carbonate raw material or a lanthanum carbonate preparation, which specifically comprises the following steps:

a. Preparation of standard curve sample: weighing a proper amount of lanthanum carbonate or lanthanum carbonate preparation sample fine powder, respectively and quantitatively adding different amounts of lanthanum carbonate hydroxide, then adding corundum into each mixture according to a certain mass ratio, and fully and uniformly mixing to prepare a series of standard curve samples;

b. Respectively scanning the standard curve samples prepared in the step a by using an X-ray diffractometer;

c. Quantitative determination: respectively reading out the diffraction intensities of the alkali lanthanum carbonate and corundum characteristics in PXRD diffraction patterns of each standard curve sample, drawing a standard curve by taking the ratio of the diffraction intensities of the alkali lanthanum carbonate and corundum characteristics as a vertical coordinate and the ratio of the mass of the alkali lanthanum carbonate and corundum in the sample as a horizontal coordinate to obtain a linear equation;

d. Preparation of a sample to be tested: fully grinding lanthanum carbonate to be detected or a lanthanum carbonate preparation to be detected, quantitatively adding corundum according to a certain proportion, and fully and uniformly mixing to prepare a sample to be detected;

e. D, scanning the sample to be detected prepared in the step d by using an X-ray diffractometer;

f. Calculating the content of the sample to be detected: respectively reading the diffraction intensities of the characteristic diffraction peaks of the alkali lanthanum carbonate and the corundum in the PXRD diffraction pattern of the sample, calculating the ratio of the diffraction intensities to the characteristic diffraction peaks of the alkali lanthanum carbonate and the corundum, and substituting the ratio into the linear equation obtained in the step d, so that the mass ratio of the alkali lanthanum carbonate to the corundum can be calculated; and then, the mass of the lanthanum carbonate hydroxide is calculated according to the mass of the corundum, and the content of the lanthanum carbonate hydroxide to be detected or the lanthanum carbonate hydroxide in the lanthanum carbonate preparation to be detected is further calculated.

the lanthanum carbonate or lanthanum carbonate formulation sample described in step a is a sample without lanthanum hydroxycarbonate.

The lanthanum carbonate hydroxide is a potential degradation impurity of a lanthanum carbonate raw material or a lanthanum carbonate preparation, and the molecular formula of the lanthanum carbonate hydroxide is La (CO)₃)OH。

The lanthanum carbonate hydroxide is selected from at least one of lanthanum carbonate hydroxide polymorphic forms.

The lanthanum carbonate hydroxide is selected from lanthanum carbonate hydroxide crystal I and lanthanum carbonate hydroxide crystal II.

In the step a, at least 5 parts of the fine powder are weighed, and the fine powder can be 5 parts, 6 parts or 7 parts.

In the step a, the part of the fine powder is preferably 6 parts.

in the step a, a proper amount of a plurality of parts of the fine powder are weighed, and lanthanum carbonate hydroxide with different amounts is quantitatively added respectively, so that each lanthanum carbonate hydroxide crystal form accounts for 0.10-10.00% of the weight of lanthanum carbonate.

The corundum is selected from alpha type Al₂O₃。

When determining lanthanum hydroxycarbonate impurities in a lanthanum carbonate feedstock:

In the step a, when the weighed fine powder is a lanthanum carbonate raw material, different amounts of lanthanum carbonate hydroxide are respectively and quantitatively added, so that each lanthanum carbonate hydroxide crystal form accounts for 0.10-3.00% of the weight of lanthanum carbonate.

In the preparation of the standard curve samples, different amounts of lanthanum carbonate hydroxide I and lanthanum carbonate hydroxide II were added to lanthanum carbonate without lanthanum carbonate hydroxide, the lanthanum carbonate hydroxide accounted for lanthanum carbonate, so that the mass fractions of lanthanum carbonate hydroxide I and lanthanum carbonate hydroxide II in the mixture were 2.7%, 1.8%, 1.44%, 0.9%, 0.36%, 0.18%, respectively, and 3.0%, 2.0%, 1.6%, 1.0%, 0.4%, 0.2%, respectively.

adding corundum into the mixture, mixing the fine powder of the lanthanum carbonate raw material with lanthanum carbonate hydroxide I and/or lanthanum carbonate hydroxide II, and adding corundum (alpha-Al)₂O₃) The mass ratio is 5-1: 1, preferably 1.5-2.5: 1, and more preferably 2: 1.

Preferred lanthanum hydroxycarbonate I has a characteristic diffraction peak, 2 Θ, at 17.6 ° or 24.3 ° or 30.2 °, more preferably at 17.6 ° or 24.3 ° 2 θ, most preferably at 17.6 ° 2 θ.

Preferred lanthanum hydroxycarbonate II has a characteristic diffraction peak, 2 Θ, at 15.7 ° or 20.3 ° or 26.0 ° or 29.8 °, more preferably at 15.7 ° or 20.3 ° 2 Θ, most preferably at 20.3 ° 2 Θ.

Preferred corundum has a characteristic diffraction peak 2 theta of 25.4 deg. or 35.0 deg. or 37.6 deg., more preferably a diffraction peak at 25.4 deg. or 35.0 deg. 2 theta, and most preferably a diffraction peak at 35.0 deg. 2 theta.

when determining lanthanum hydroxycarbonate impurities in lanthanum carbonate formulations:

In the step a, when the weighed fine powder is a lanthanum carbonate preparation, different amounts of lanthanum carbonate hydroxide are respectively and quantitatively added, so that each lanthanum carbonate hydroxide crystal form accounts for 0.50-10.00% of the weight of lanthanum carbonate.

Different amounts of lanthanum I carbonate hydroxide and lanthanum II carbonate hydroxide were added to the lanthanum carbonate formulation fines without lanthanum carbonate hydroxide during the preparation of the standard curve samples to provide a mixture having a mass fraction of lanthanum I carbonate hydroxide of 8.16%, 6.8%, 5.44%, 3.4%, 1.36%, 0.68%, and a mass fraction of lanthanum II carbonate hydroxide of 7.12%, 7.6%, 6.08%, 3.8%, 1.52%, 0.76%, respectively.

adding corundum into the mixture, mixing the fine powder of the lanthanum carbonate preparation with lanthanum carbonate hydroxide I and/or lanthanum carbonate hydroxide II, and adding corundum (alpha-Al)₂O₃) The mass ratio is 10-1: 1, preferably 4-6: 1, and more preferably 5: 1.

Preferred lanthanum hydroxycarbonate I has a characteristic diffraction peak, 2 Θ, at 17.6 ° or 24.3 ° or 30.2 °, more preferably at 17.6 ° or 24.3 ° 2 θ, most preferably at 17.6 ° 2 θ.

preferred lanthanum hydroxycarbonate II has a characteristic diffraction peak, 2 Θ, at 15.7 ° or 20.3 ° or 26.0 ° or 29.8 °, more preferably at 15.7 ° or 26.0 ° 2 Θ, and most preferably at 26.0 ° 2 Θ.

Preferred corundum has a characteristic diffraction peak 2 theta of 25.4 deg. or 35.0 deg. or 37.6 deg., more preferably a diffraction peak at 25.4 deg. or 35.0 deg. 2 theta, and most preferably a diffraction peak at 35.0 deg. 2 theta.

In the assay method provided by the invention, the linear equation of the preferred standard curve in step c is as follows:

y is ax + b, wherein

y is I_j/I_SteelNamely the diffraction intensity ratio of the characteristic peaks of alkali lanthanum carbonate I and/or alkali lanthanum carbonate II and corundum in PXRD spectrogram,

x is m_j/m_Steeli.e. the ratio of lanthanum carbonate I and/or lanthanum hydroxycarbonate II in the mixture to the mass of corundum,

The slope a isnamely, the diffraction reference intensity of the alkali lanthanum carbonates I and (or) II in PXRD spectrogram and the characteristic peak relative to corundum.

The lanthanum carbonate preparation provided by the invention comprises but is not limited to a lanthanum carbonate chewable tablet, lanthanum carbonate particles, a lanthanum carbonate dry suspension, a lanthanum carbonate capsule and a lanthanum carbonate dispersible tablet.

The powder X-ray diffractometer disclosed by the invention can be selected from X-ray diffractometers conventional in the field, and the scanning measurement conditions are preferably as follows: rigaku D/max-rA X-ray diffractometer or other brands of X-ray diffractometers, Cu Ka targets, 40KV and 100mA pipe pressure and pipe flow respectively are adopted; the divergence slit and the anti-divergence slit are 1 degree, the receiving slit is 0.30mm, the detector is a sodium iodide scintillation counter, the theta-2 theta is in linkage continuous scanning, the scanning speed is 2 degrees/minute (0.02 degrees step width), and the scanning range is 3-50 degrees, preferably 9-40 degrees.

The X-ray diffractometer of the invention is calibrated, and of course, when different powder X-ray diffractometers are used, and/or under the same experiment conditions, the characteristic diffraction peak 2 theta angle of various substances in the invention has deviation of +/-0.01 degrees or +/-0.02 degrees; as will be appreciated by those skilled in the art.

the detection method provided by the invention does not necessarily need to be carried out according to the sequence of the steps, and the sequence of the steps can be adjusted according to actual conditions, which is also within the protection scope of the invention. For example, the following steps can be followed:

a. Firstly, respectively preparing a standard curve sample and a sample to be detected;

b. Scanning a standard curve sample and a sample to be detected by powder X-ray diffraction (PXRD));

c. Performing quantitative determination, and drawing to obtain two standard curves and two linear equations;

d. and calculating the content of the sample to be detected.

specifically, the steps of the assay method provided by the invention are as follows:

a. Preparation of Standard Curve samples

Adding different amounts of basic lanthanum carbonate I and basic lanthanum carbonate II into lanthanum carbonate without basic lanthanum carbonate or a preparation thereof, and adding internal standard reference substance corundum (alpha-Al) according to a certain proportion of the mass of the mixture₂O₃) And grinding to mix uniformly to prepare a series of standard curve samples.

b. Preparation of samples to be tested

Adding internal standard reference substance corundum (alpha-Al) into lanthanum carbonate or its preparation (ground into fine powder in advance) powder to be measured according to a certain proportion of its mass₂O₃) Grinding to mix uniformly to obtain the test sample.

c. Powder X-ray diffraction (PXRD)) scan

And respectively preparing a series of standard curve samples and samples to be detected, and then scanning and measuring by adopting a powder X-ray diffractometer under certain detection conditions.

d. Quantitative determination

And reading diffraction intensities of characteristic diffraction peaks of lanthanum carbonate I, lanthanum carbonate II and corundum in each standard curve sample PXRD spectrogram, drawing to obtain two standard curves and two linear equations by taking the ratio of the diffraction intensities of the lanthanum carbonate I and the lanthanum carbonate II in each PXRD spectrogram to the characteristic diffraction peaks of corundum as a vertical coordinate and the ratio of the lanthanum carbonate I and the lanthanum carbonate II in each standard curve sample to the mass of corundum as a horizontal coordinate.

e. calculating the content of the sample to be measured

And respectively substituting the specific values of the diffraction intensities of the characteristic diffraction peaks of the alkali lanthanum carbonate I and the alkali lanthanum carbonate II in the PXRD spectrogram of the sample to be tested and corundum into the linear equations to calculate the mass ratio of the alkali lanthanum carbonate I and the alkali lanthanum carbonate II in the sample to be tested to the corundum respectively, so that the content of the alkali lanthanum carbonate I and the alkali lanthanum carbonate II in the sample to be tested can be calculated.

Advantageous technical effects

The method for detecting the lanthanum hydroxycarbonate has the advantages of simple and convenient operation, wide linear range, good linear relation, good precision, high accuracy, good durability and high detection sensitivity, and can simply, quickly and accurately detect the lanthanum hydroxycarbonate impurities in the lanthanum hydroxycarbonate raw material and the preparation thereof.

the detection sensitivity is high: when analyzing and detecting the lanthanum carbonate hydroxide impurities in the lanthanum carbonate raw material, the minimum detection limit of lanthanum carbonate hydroxide I is about 0.21 percent, the quantitative limit is about 0.63 percent, the minimum detection limit of lanthanum carbonate hydroxide II is about 0.18 percent, and the quantitative limit is about 0.56 percent, which are calculated by mass fraction in the lanthanum carbonate raw material;

When the impurities of the lanthanum carbonate hydroxide in the lanthanum carbonate preparation are analyzed and detected, the minimum detection limit of the lanthanum carbonate hydroxide I is about 0.10 percent, the quantitative limit is about 0.17 percent, the minimum detection limit of the lanthanum carbonate hydroxide II is about 0.29 percent, and the quantitative limit is about 0.51 percent, which are calculated by mass fraction in the lanthanum carbonate preparation;

The linear range is wide, and the linear relation is good: when the lanthanum carbonate hydroxide impurities in the lanthanum carbonate raw material are analyzed and detected, the lanthanum carbonate hydroxide I has a good linear relation in the range of 0.68-34% by mass of the lanthanum carbonate raw material, the correlation coefficient is 0.9986, the lanthanum carbonate hydroxide II has a good linear relation in the range of 0.76-38% by mass of the lanthanum carbonate raw material, and the correlation coefficient is 0.9984.

When the lanthanum carbonate hydroxide impurity in the lanthanum carbonate preparation is analyzed and detected, the lanthanum carbonate hydroxide I has a good linear relation in the range of 0.18-10.8% in the mass fraction of the lanthanum carbonate hydroxide I in the preparation, the correlation coefficient is 0.9973, the lanthanum carbonate hydroxide II has a good linear relation in the range of 0.20-12% in the mass fraction of the lanthanum carbonate hydroxide II in the preparation, and the correlation coefficient is 0.9963.

Drawings

FIG. 1 example 1 PXRD spectrum of lanthanum hydroxycarbonate I

FIG. 2 PXRD spectrum of example 1 lanthanum II hydroxycarbonate

FIG. 3 PXRD spectrum of lanthanum carbonate feedstock in example 1

FIG. 4 PXRD spectrum of lanthanum carbonate chewable tablet fine powder of example 1

FIG. 5 example 1 corundum (. alpha. -Al)₂O₃) PXRD spectrogram

FIG. 6 example 1 PXRD spectrum of lanthanum carbonate + lanthanum hydroxycarbonate I + lanthanum hydroxycarbonate II + corundum mixture

FIG. 7 example 1 PXRD spectrum of lanthanum carbonate chewable tablet + lanthanum carbonate hydroxide I + lanthanum carbonate hydroxide II + corundum mixture

FIG. 8 example 1 (FIGS. 1-3, FIGS. 5-6) PXRD spectrogram superposition

FIG. 9 example 1 (FIGS. 1-2, FIGS. 4-5, and FIG. 7) PXRD spectrum superposition

FIG. 10 example 2 PXRD spectrum overlay of lanthanum carbonate raw material standard curve sample

FIG. 11: standard curve and linear equation for lanthanum hydroxycarbonate I

FIG. 12: standard curve and linear equation for lanthanum carbonate hydroxide II

FIG. 13 example 5 interference test of lanthanum carbonate raw material PXRD spectrum of damp-heat 5-day sample

FIG. 14 example 5 interference test of lanthanum carbonate raw material PXRD spectrum of wet heat 10-day sample

Detailed Description

for the purpose of facilitating an understanding of the present disclosure, the following further describes the technical solutions of the present invention with reference to specific examples, but the present invention is not limited in any way.