CN110579499A - Method for detecting lanthanum carbonate or lanthanum hydroxycarbonate impurity in preparation thereof - Google Patents
Method for detecting lanthanum carbonate or lanthanum hydroxycarbonate impurity in preparation thereof Download PDFInfo
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N23/00—Investigating or analysing materials by the use of wave or particle radiation, e.g. X-rays or neutrons, not covered by groups G01N3/00 – G01N17/00, G01N21/00 or G01N22/00
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N23/00—Investigating or analysing materials by the use of wave or particle radiation, e.g. X-rays or neutrons, not covered by groups G01N3/00 – G01N17/00, G01N21/00 or G01N22/00
- G01N23/20—Investigating or analysing materials by the use of wave or particle radiation, e.g. X-rays or neutrons, not covered by groups G01N3/00 – G01N17/00, G01N21/00 or G01N22/00 by using diffraction of the radiation by the materials, e.g. for investigating crystal structure; by using scattering of the radiation by the materials, e.g. for investigating non-crystalline materials; by using reflection of the radiation by the materials
- G01N23/20008—Constructional details of analysers, e.g. characterised by X-ray source, detector or optical system; Accessories therefor; Preparing specimens therefor
- G01N23/2005—Preparation of powder samples therefor
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2223/00—Investigating materials by wave or particle radiation
- G01N2223/05—Investigating materials by wave or particle radiation by diffraction, scatter or reflection
- G01N2223/056—Investigating materials by wave or particle radiation by diffraction, scatter or reflection diffraction
- G01N2223/0568—Investigating materials by wave or particle radiation by diffraction, scatter or reflection diffraction spectro-diffractometry
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2223/00—Investigating materials by wave or particle radiation
- G01N2223/10—Different kinds of radiation or particles
- G01N2223/101—Different kinds of radiation or particles electromagnetic radiation
- G01N2223/1016—X-ray
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- G—PHYSICS
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- G01N2223/00—Investigating materials by wave or particle radiation
- G01N2223/60—Specific applications or type of materials
- G01N2223/652—Specific applications or type of materials impurities, foreign matter, trace amounts
Abstract
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.
Description
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 Ij/ISteelNamely 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 mj/mSteeli.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.
Example 1
specificity test
The experimental conditions of the instrument are as follows: the Rigaku D/max-rA X-ray diffractometer adopts a Cu Kalpha target, and the pipe pressure and the pipe flow are respectively 40KV and 100 mA; 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 9-40 degrees.
The test steps are as follows: respectively preparing sample of 1) lanthanum carbonate hydroxide I, 2) lanthanum carbonate hydroxide II, 3) lanthanum carbonate raw material (without the lanthanum carbonate hydroxide I and II), 4) lanthanum carbonate chewable tablet fine powder, 5) corundum, 6) lanthanum carbonate, lanthanum carbonate hydroxide I, lanthanum carbonate hydroxide II and corundum mixture, 7) lanthanum carbonate chewable tablet fine powder, lanthanum carbonate hydroxide I, lanthanum carbonate hydroxide II and corundum mixture, carrying out PXRD scanning, and recording spectrograms, wherein the results are respectively shown in figures 1-7.
Figure 1 shows that under the test conditions, the characteristic diffraction peak 2 theta angle of the lanthanum carbonate hydroxide I is as follows: 17.620 °, 24.321 °, 30.239 °;
Figure 2 shows that under the test conditions, the characteristic diffraction peak 2 theta angle of the lanthanum carbonate hydroxide II is as follows: 15.740 degrees, 20.399 degrees and 20.621 degrees (double peaks), 23.699 degrees, 26.120 degrees and 29.860 degrees, and a small amount of characteristic diffraction peaks (17.719 degrees, 24.379 degrees and 30.301 degrees) of the lanthanum carbonate hydroxide 1 can be seen from the spectrum, and the lanthanum carbonate hydroxide II contains a small amount of lanthanum carbonate hydroxide I.
FIG. 3 shows the PXRD spectrum of the lanthanum carbonate feedstock under this experimental condition
The PXRD patterns of lanthanum carbonate, lanthanum hydroxycarbonate I and II in the present invention are substantially identical to those described in the patent CN 101484798.
FIG. 5 shows that under the test conditions corundum (. alpha. -Al)2O3) The characteristic diffraction peak of (2) is the angle of 2 theta: 25.481 °, 35.061 °, 37.681 °.
FIGS. 6 and 7 show that under these test conditions, both mixtures exhibit characteristic diffraction peaks for lanthanum carbonate hydroxide I, lanthanum carbonate hydroxide II and corundum, and that both characteristic peaks are free of interference and can be detected analytically.
Example 2
Linear and range test
a. fully grinding a lanthanum carbonate sample without the basic lanthanum carbonates I and II to obtain lanthanum carbonate sample fine powder;
b. Adding different qualities of basic lanthanum carbonate I and basic lanthanum carbonate II into lanthanum carbonate without the basic lanthanum carbonate I and the basic lanthanum carbonate II respectively,
Standard curve sample 1: the lanthanum carbonate contains 8.16 percent of alkali lanthanum carbonate I and 9.12 percent of alkali lanthanum carbonate II;
Standard curve sample 2: the lanthanum carbonate contains alkali lanthanum carbonate I6.8% and alkali lanthanum carbonate II 7.6%;
standard curve sample 3: the lanthanum carbonate contains 5.44% of alkali lanthanum carbonate I and 6.08% of alkali lanthanum carbonate II;
Standard curve sample 4: the lanthanum carbonate contains 3.4% of alkali lanthanum carbonate I and 3.8% of alkali lanthanum carbonate II;
standard curve sample 5: 1.36 percent of alkali lanthanum carbonate I and 1.52 percent of alkali lanthanum carbonate II in the lanthanum carbonate;
Standard curve sample 6: the lanthanum carbonate contains 0.68 percent of alkali lanthanum carbonate I and 0.76 percent of alkali lanthanum carbonate II.
adding corundum with a certain mass, wherein the mass ratio of the mass of the lanthanum carbonate + lanthanum carbonate I + lanthanum carbonate II mixture to the mass of the corundum is 2: 1, grinding for 10 minutes to uniformly mix the mixture, and respectively preparing a series of standard curve samples:
c. respectively scanning diffraction spectra of the standard curve samples prepared in the step b by an X-ray diffractometer (figure 10),
d. Diffraction intensities of characteristic diffraction peaks (17.6 degrees, 20.3 degrees and 35.0 degrees respectively) of lanthanum carbonate hydroxide I, lanthanum carbonate hydroxide II and corundum in a PXRD diffraction spectrum are respectively read.
the mass ratio of the lanthanum carbonate hydroxide I to the corundum in the standard curve sample after correction is obtained;
the mass ratio of the lanthanum carbonate hydroxide II to the corundum in the standard curve sample after correction is obtained;
PXRD spectrogram of standard curve sampleThe ratio of I17.6-degree characteristic diffraction peak of lanthanum carbonate hydroxide to 35.0-degree characteristic diffraction peak diffraction intensity of corundum;
is the ratio of diffraction intensity of a 20.3-degree characteristic diffraction peak of alkali lanthanum carbonate II and a 35.0-degree characteristic diffraction peak of corundum in a PXRD spectrogram of a standard curve sample;
And performing linear regression on the mass ratio of the comparison of the diffraction intensity of the characteristic diffraction peak of the basic lanthanum carbonate I and the corundum, and drawing a standard curve of the basic lanthanum carbonate I to obtain a linear equation of the basic lanthanum carbonate I. The standard curve and linear equation for lanthanum hydroxycarbonate I are shown in figure 11.
And performing linear regression on the mass ratio of the comparison of the diffraction intensity of the characteristic diffraction peak of the lanthanum carbonate II and the corundum to draw a standard curve of the lanthanum carbonate II to obtain a linear equation of the lanthanum carbonate II. The standard curve and linear equation for lanthanum II carbonate hydroxide are shown in FIG. 12.
And (4) conclusion: in the lanthanum carbonate, the alkali lanthanum carbonate I is 0.68-8.16%, the linear relation between the diffraction intensity of the characteristic diffraction peak of the alkali lanthanum carbonate I and the diffraction intensity of corundum is good, and the linear equation is as follows: y is 3.1636x-0.0045 (r)2＝0.9951)：
In the lanthanum carbonate, the alkali lanthanum carbonate II accounts for 0.76-9.12%, the linear relation between the diffraction intensity of the characteristic diffraction peak of the alkali lanthanum carbonate II and the diffraction intensity of corundum compared with the mass ratio of the alkali lanthanum carbonate II and the corundum is good, and the linear equation is as follows: y is 2.4324x-0.0046 (r)2＝0.9992)
Example 3
Repeatability test
When the repeatability is inspected, 6 samples are prepared in parallel according to the method of the standard curve sample 2, after PXRD is scanned respectively, the measurement results are substituted into the standard curve equation of the embodiment 2, the recovery amount of the basic lanthanum carbonate I and the recovery amount of the basic lanthanum carbonate II are calculated, and the RSD of the calculation results among the 6 samples is inspected, and the results are as follows:
and (4) conclusion: the test results show that the method has good repeatability.
Example 4
Results of sample measurement
Lanthanum carbonate degraded under moist heat conditions (60 ℃/RH 92.5%) for both 5 days and 10 days to yield the two impurities, so the samples after the two moist heat conditions failed the degradation were determined.
the test determination procedure is as follows:
(a-d) determining the standard curve by the method of example 2 to obtain a linear equation;
The linear equation for lanthanum hydroxycarbonate I is as follows:
y＝3.1636x-0.0045
The linear equation for lanthanum hydroxycarbonate II is as follows:
y＝2.4324x-0.0064
(e) adding corundum into a sample to be tested, wherein the mass ratio of the sample to be tested to the corundum is 2: 1, and grinding for 5 minutes to uniformly mix the sample to be tested and the corundum to obtain a test sample.
(f) PXRD were separately scanned under the same test conditions as in example 2 and scanned twice in parallel (fig. 13 and 14 show PXRD patterns for a 5-day sample in a lanthanum carbonate raw material interference test in fig. 13, and a 10-day sample in a lanthanum carbonate raw material interference test in fig. 14).
(g) And reading the ratio of the characteristic diffraction peaks of the basic lanthanum carbonate I (17.6 degrees) and the basic lanthanum carbonate II (20.3 degrees) in the PXRD spectrogram of the sample to corundum (35.0 degrees), substituting the values into a standard curve linear equation to obtain the mass ratio of the basic lanthanum carbonate I and the basic lanthanum carbonate II to the corundum respectively, and calculating the content of the basic lanthanum carbonate I and the basic lanthanum carbonate II in the lanthanum carbonate after degradation and destruction.
Calculation of measurement results
determination results of alkali lanthanum carbonate impurities in lanthanum carbonate raw material degraded and destroyed under damp and hot conditions for 5 days and 10 days
Claims (22)
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 Ij/ISteelNamely 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 mj/mSteelI.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).
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