CN109632932B - Method for analyzing elements in lamivudine preparation - Google Patents
Method for analyzing elements in lamivudine preparation Download PDFInfo
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- G—PHYSICS
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- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
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- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/44—Sample treatment involving radiation, e.g. heat
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
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Abstract
The invention relates to the technical field of lamivudine detection, in particular to an element analysis method in a lamivudine preparation. The method comprises the following steps: (1) preparation of a sample to be tested: taking a lamivudine tablet to be detected, adding mixed acid for dissolving, digesting and fixing the volume to obtain a liquid to be detected; (2) adding a standard solution to a sample: taking the lamivudine tablet to be measured and the sodium element and magnesium element standard mother liquor, adding mixed acid for dissolving, digesting and fixing volume to obtain a sample standard solution; (3) inductively coupled plasma mass spectrometry: detecting and analyzing the standard solution and the sample solution by using an inductively coupled plasma mass spectrometer; (4) and (4) analyzing results: and (5) standard curve drawing and method verification.
Description
Technical Field
The invention relates to the technical field of lamivudine detection, in particular to an element analysis method in a lamivudine preparation.
Background
Hepatitis B is an epidemic infectious disease with high morbidity, strong infectivity and serious harm to human health, and is a global public health problem. More than 30 million people die of hepatitis B related complications every year in China, wherein the 5-year fatality rates of chronic hepatitis B, and liver cirrhosis in compensatory and decompensated stages are 0% -2%, 14% -20% and 70% -86% respectively. The total cost for treating hepatitis B is over 1000 hundred million in China every year, and chronic hepatitis B and complications thereof bring great disease burden to patients and also bring heavy economic burden to society and individuals.
Lamivudine is an antiviral drug belonging to nucleoside reverse transcriptase inhibitors, was first developed by Biochem Pharma, canada, and was first marketed in 1995 by Glaxo Wellcome, uk, for the treatment of HBV infection, in 1996 in uk, and was approved by imported registration in china 1999.
Lamivudine has strong inhibitory effect on Hepatitis B Virus (HBV) in vitro and in experimental infected animals. Lamivudine is metabolized in HBV infected cells and normal cells to produce Lamivudine triphosphate, which is the active form of Lamivudine, both an inhibitor of HBV polymerase and a substrate for this polymerase. Lamivudine has little effect on DNA content of mammalian cells. Lamivudine has no obvious toxicity to the structure, DNA content and function of mitochondria. The result of HBV DNA detection in serum of most hepatitis B patients shows that lamivudine can rapidly inhibit HBV replication, and the inhibition effect lasts for the whole treatment process. Simultaneously, the serum transaminase is reduced to be normal, and the long-term application can obviously improve the inflammatory change of liver necrosis and reduce or prevent the progress of liver fibrosis.
Because the prior lamivudine is protected by patents, the raw materials and the preparation thereof are imported in China. In the process of preparing the lamivudine tablet, a certain amount of auxiliary materials are added to successfully tablet, and the main auxiliary materials are sodium carboxymethyl starch, magnesium stearate, silicon dioxide and the like, and the auxiliary materials interfere with the test result in the process of measuring the component content of lamivudine. In order to effectively control the quality of the medicine product, it is necessary to establish a method for measuring the content of the components in the medicine and checking related substances.
Disclosure of Invention
Aiming at the technical problems, the invention provides a method for analyzing elements in a lamivudine preparation, which comprises the following steps:
(1) preparation of a sample to be tested: taking a lamivudine tablet to be detected, adding mixed acid for dissolving, digesting and fixing the volume to obtain a liquid to be detected;
(2) adding a standard solution to a sample: taking the lamivudine tablet to be measured and the sodium element and magnesium element standard mother liquor, adding mixed acid for dissolving, digesting and fixing volume to obtain a sample standard solution;
(3) inductively coupled plasma mass spectrometry: detecting and analyzing the standard solution and the sample solution by using an inductively coupled plasma mass spectrometer;
(4) and (4) analyzing results: and (5) standard curve drawing and method verification.
As a preferred technical scheme, the mixed acid comprises concentrated nitric acid and hydrofluoric acid.
As a preferred technical solution, the volume ratio of the concentrated nitric acid to the hydrofluoric acid is 2: 2.
as a preferred technical solution, the mixed acid further includes perchloric acid.
As a preferred technical solution, the volume ratio of the mixing is concentrated nitric acid: hydrofluoric acid: perchloric acid 2: 2: 1.
as a preferable technical scheme, the lamivudine tablet to be measured contains a silicon dioxide component.
As a preferred technical scheme, the preparation process of the sample to be detected is as follows: putting lamivudine tablets to be tested into a beaker, adding 5ml of mixed acid, digesting at a certain temperature by using a graphite furnace, cooling to room temperature, transferring to a 50ml volumetric flask, fixing the volume to the scale by using water, and shaking up for later use; transferring the solution into a volumetric flask with the volume of 0.1ml to 10ml, fixing the volume to the scale with 2% nitric acid, shaking up, and preparing three parts in parallel to obtain the product.
As a preferable technical scheme, the digestion temperature is 115-125 ℃.
As a preferable technical solution, the elements to be analyzed are sodium element and magnesium element.
As a preferable technical scheme, the test concentration range of the sodium element is 0.1-2.0 mg/L; the test range of the magnesium element is 0.05-1.0 mg/L.
Has the advantages that: the test method provided by the invention has the advantages of high sensitivity, low detection limit and good reproducibility, and can accurately and precisely determine the sodium and magnesium elements in the specific lamivudine by combining with a chemical pretreatment means. The method provided by the invention is based on the selection of high abundance and small interference, and has the advantages of high determination speed, high accuracy and good precision under the condition of eliminating matrix interference and mass spectrum interference.
Detailed Description
The technical features of the technical solutions provided by the present invention will be further clearly and completely described below with reference to the specific embodiments, and it should be apparent that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The words "preferred", "preferably", "more preferred", and the like, in the present invention, refer to embodiments of the invention that may provide certain benefits, under certain circumstances. However, other embodiments may be preferred, under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful, nor is it intended to exclude other embodiments from the scope of the invention.
It should be understood that other than in any operating examples, or where otherwise indicated, all numbers expressing, for example, quantities of ingredients used in the specification and claims are to be understood as being modified in all instances by the term "about".
Aiming at the technical problems, the invention provides a method for analyzing elements in a lamivudine preparation, which comprises the following steps:
(1) preparation of a sample to be tested: taking a lamivudine tablet to be detected, adding mixed acid for dissolving, digesting and fixing the volume to obtain a liquid to be detected;
(2) adding a standard solution to a sample: taking the lamivudine tablet to be measured and the sodium element and magnesium element standard mother liquor, adding mixed acid for dissolving, digesting and fixing volume to obtain a sample standard solution;
(3) inductively coupled plasma mass spectrometry: detecting and analyzing the standard solution and the sample solution by using an inductively coupled plasma mass spectrometer;
(4) and (4) analyzing results: and (5) standard curve drawing and method verification.
In some embodiments, the elements to be analyzed are sodium and magnesium.
In some embodiments, the test concentration of elemental sodium ranges from 0.1 to 2.0 mg/L; the test range of the magnesium element is 0.05-1.0 mg/L.
1. The inductively coupled plasma mass spectrometry of the invention is ICP-MS.
The instrument parameters are shown in table 1 below:
standard 1 Instrument parameters
The inductively coupled plasma mass spectrometry is to use an inductively coupled plasma mass spectrometer to detect and analyze a standard solution and residues containing a sample to be detected.
And (3) testing conditions are as follows: output power of high frequency generator: 1200W; plasma gas flow rate: 18L/min; flow rate of auxiliary gas: 0.50-1.5L/min; flow rate of the atomizer: 0.70-1.0L/min.
In a preferred embodiment, the plasma gas flow rate during the sample detection is: 18L/min; flow rate of auxiliary gas: 1.2L/min; flow rate of the atomizer: 0.83L/min.
The applicant finds that the ratio of the atomizing airflow rate to the auxiliary airflow rate can be adjusted to help improve the yield of magnesium ions, thereby improving the limit of quantitation of detection. Since only elements having a secondary ionization energy lower than the primary ionization energy (16eV) of the plasma gas (argon) can form significant doubly charged ions, the yield is improved by controlling the size of the atomizing gas flow rate and the ratio thereof to the auxiliary gas flow rate, thereby increasing the limit of quantitation of detection.
2. Preparation of a sample to be tested: in some embodiments, the sample to be tested is prepared by the following steps: putting lamivudine tablets to be tested into a beaker, adding 5ml of mixed acid, digesting at a certain temperature by using a graphite furnace, cooling to room temperature, transferring to a 50ml volumetric flask, fixing the volume to the scale by using water, and shaking up for later use; transferring a volumetric flask with the volume of 0.1ml to 10ml of the solution, fixing the volume to the scale with 2% nitric acid, shaking up, and preparing three parts in parallel; preferably, the digestion temperature is 115-125 ℃; more preferably, the temperature is 120 ℃.
In some embodiments, the mixed acid comprises concentrated nitric acid and hydrofluoric acid; preferably, the volume ratio of the concentrated nitric acid to the hydrofluoric acid is 2: 2; more preferably, the mixed acid further comprises perchloric acid; further preferably, the volume ratio of the mixture is concentrated nitric acid: hydrofluoric acid: perchloric acid 2: 2: 1.
preferably, performing microwave digestion on the sample subjected to the digestion by the mixed acid; further preferably, a step of acid-dispelling is added after the microwave digestion. The specific acid-removing step is to heat the sample to 60 ℃ for about 1.5 hours, and basically no yellow smoke exists.
The concentrated nitric acid, the hydrofluoric acid, the perchloric acid and the like in the invention are acids with specification parameters well known to those skilled in the art, and for example, the concentrated nitric acid is concentrated nitric acid with the content of 67-70 wt%.
The applicant finds that when the mixed acid is used for dissolving and digesting the medicine, the digestion rate of the sample can be increased, and the accuracy and the sensitivity of the sample test are improved. The possible reason for this is that hydrofluoric acid has a stronger oxidizing property than nitric acid, and can accelerate the digestion speed of lamivudine tablets; on the other hand, hydrofluoric acid reacts with silicon dioxide in lamivudine, so that Na compounds and Mg compounds are more likely to react with nitric acid and are fully dissolved out, and the measurement accuracy is improved; and, the reaction produces SiF4Is a gas, thereby reducing the interference of the matrix and improving the sensitivity. In addition, on one hand, the oxidation capacity is synergistically improved by compounding the three acids, and the digestion speed is further accelerated; on the other hand, hydrofluoric acid in the water can be prevented from corroding the instrument.
In some embodiments, the lamivudine tablet to be tested contains a silica component.
The lamivudine needs to have good fluidity, compressibility, moldability and the like in the process of preparing the tablet, so that corresponding auxiliary materials such as a filler, a disintegrant, a lubricant and the like need to be added in the process of tabletting the main drug component, wherein the silicon dioxide is a common drug tabletting lubricant, and the property of the silicon dioxide is very stable, and the silicon dioxide is not fully digested when being digested by a conventional means, so that the test result of elements such as sodium, magnesium and the like coated in the silicon dioxide is influenced. The silicon dioxide is a conventional auxiliary material in lamivudine, and the content of the silicon dioxide is 0.05-2wt% of the weight of the lamivudine.
Preparing 2% nitric acid: adding a proper amount of water into a beaker, measuring 5ml of concentrated nitric acid into a 100ml beaker, diluting with water, cooling, transferring into a 250ml measuring flask, fixing the volume to the scale with water, and shaking up for later use.
3. Preparation of a linear solution: respectively transferring a certain volume of sodium element mother liquor and a certain volume of magnesium element mother liquor into a 10mL volumetric flask by using a pipette, metering the volume by using 2% nitric acid, and then shaking up for later use. Specific formulation parameters are shown in table 2.
TABLE 2 Linear solution formulation parameters
The concentration of the sodium element mother liquor is 10 mg/L; the concentration of the magnesium element mother liquor is 10 mg/L. The sodium element standard solution is purchased from national nonferrous metal testing center with batch number/unique identification 17B055-1, and the magnesium element standard solution is purchased from national nonferrous metal testing center with batch number/unique identification 175052-2.
Process blank solution: adding a proper amount of water into a beaker, measuring 5ml of concentrated nitric acid into a 100ml beaker, diluting with water, cooling, transferring into a 250ml measuring flask, and fixing the volume to the scale with water to obtain the 2% nitric acid.
Adding a standard solution to a sample: weighing about 250mg of the medicine (the lamivudine tablet self-made preparation 20171001) without the coating in a beaker, adding 5ml of concentrated nitric acid, heating by a graphite furnace at 120 ℃, until the medicine is completely digested, cooling to room temperature, transferring to a 50ml volumetric flask, fixing the volume to the scale by water, and shaking up for later use; transferring the solution into a volumetric flask of 0.1ml to 10ml, adding 0.1ml of 10mg/L sodium element standard solution and 0.05ml of 10mg/L magnesium element standard solution, fixing the volume to 10ml by using a 2% nitric acid solution, shaking up, and preparing 3 parts in parallel.
4. And (4) analyzing results: and (5) standard curve drawing and method verification.
The RSD according to the present invention is expressed as relative standard deviation. The standard curve was plotted according to the parameters of table 2, and the results are shown in the following table:
TABLE 3 Linear and Range test results (Strength) for Na element and Mg element
Detection limit and quantitation limit experiments: and (3) testing the solution to be tested according to the method provided by the invention, continuously measuring the sample solution for 7 times, and measuring, analyzing and recording the response values of the sodium element and the magnesium element by ICP-MS. Continuously measuring the 3-time standard deviation (3SD) of the strength of the test solution as a detection limit; the limit of quantitation was 10 times the standard deviation (10SD) of the strength of the test solution measured continuously. Linear equation is substituted for calculation, and LOD & LOQ concentrations of sodium element and magnesium element are obtained, and specific data are shown in Table 4.
TABLE 4 detection limit and quantitation limit test data (Strength) for Na element and Mg element
The detection limit and the quantitative limit result are calculated according to the following formulaLOD) And quantitative limit (C)LOQ)。
LOD＝3SD
LOQ＝10SD
CLOD(mg/L)＝LOD/K
CLOQ(mg/L)＝LOQ/K
Remarking: k is the linear slope; SD: standard deviation of solution strength of sample 7 times.
And (3) accuracy test: the sample spiking solutions were tested according to the method of the present invention, wherein the spiking ranges of sodium and magnesium were 50%, 100%, and 150%, and the recovery rates were determined at different concentrations. The specific configuration parameters are detailed in table 5.
TABLE 5 sample spiking solution formulation parameters in accuracy tests
And (3) repeatability test: the blank solution and the sample standard adding solution in the process are tested, the standard adding ranges of the sodium element and the magnesium element are 50%, 100% and 150%, and the specific configuration parameters are detailed in table 5.
And (3) precision experiment: and adding a standard solution into the sample, wherein the concentration of the sodium element is 1.0mg/L, and the concentration of the magnesium element is 0.5 mg/L. The sample was used to add a standard solution to perform an intermediate precision test, and different persons performed two tests on different dates, 6 sets of tests were performed in parallel each time, and RSD results were obtained.
The present invention will be specifically described below by way of examples. It should be noted that the following examples are only for illustrating the present invention and should not be construed as limiting the scope of the present invention, and that the insubstantial modifications and adaptations of the present invention by those skilled in the art based on the above disclosure are still within the scope of the present invention.
In addition, the starting materials used are all commercially available, unless otherwise specified.
Examples
Example 1
Embodiment 1 provides a method for analyzing elements in a lamivudine preparation, comprising the steps of:
(1) preparation of a sample to be tested: taking a lamivudine tablet to be detected, adding mixed acid for dissolving, digesting and fixing the volume to obtain a liquid to be detected;
(2) preparing a sample labeling solution: taking the lamivudine tablet to be measured and the sodium element and magnesium element standard mother liquor, adding mixed acid for dissolving, digesting and fixing volume to obtain a sample standard solution;
(3) inductively coupled plasma mass spectrometry: detecting and analyzing the standard solution and the sample solution by using an inductively coupled plasma mass spectrometer;
(4) and (4) analyzing results: and (5) standard curve drawing and method verification.
The preparation steps of the sample to be detected in the step (1) specifically comprise: putting the lamivudine tablet to be detected into a beaker, adding 5ml of mixed acid, digesting at a certain temperature by using a graphite furnace, continuing microwave digestion (the specific steps are carried out according to conventional operation) and dispelling acid, cooling to room temperature (25 ℃), transferring to a 50ml volumetric flask, fixing the volume to the scale by using water, and shaking up for later use; transferring a volumetric flask with the volume of 0.1ml to 10ml of the solution, fixing the volume to the scale with 2% nitric acid, shaking up, and preparing three parts in parallel; the digestion temperature is 120 ℃; the mixed acid is concentrated nitric acid: hydrofluoric acid: perchloric acid 2: 2: 1 (volume ratio); the lamivudine tablet contains 0.4 wt% of silicon dioxide;
the preparation steps of the sample labeling solution in the step (2) comprise: respectively transferring a certain volume of sodium element mother liquor and a certain volume of magnesium element mother liquor into a 10mL volumetric flask by using a pipette, metering the volume by using 2% nitric acid, and then shaking up for later use. Specific formulation parameters are shown in table 2.
And (3) inductively coupled plasma mass spectrometry is to use an inductively coupled plasma mass spectrometer to detect and analyze the sample adding standard solution and the sample to be detected. And (3) testing conditions are as follows: output power of high frequency generator: 1200W; plasma gas flow rate: 18L/min; flow rate of auxiliary gas: 1.2L/min; flow rate of the atomizer: 0.83L/min.
The analysis of the result of the step (4) comprises
1) Drawing a standard curve: the linear and range data and the results of the linear equations for the sodium and magnesium were determined for the linear solutions according to the methods provided by the present invention and are detailed in tables 6 and 7. It can be seen that the linearity of the sodium element and the magnesium element is good, and the linear correlation coefficient is more than 0.995, which meets the requirements. As the linear equations of the sodium element and the magnesium element both zero, and the correlation coefficient is more than or equal to 0.995, the linear ranges of the sodium element and the magnesium element are respectively 0 mg/L-2.0 mg/L and 0 mg/L-1.0 mg/L.
TABLE 6 Linear and Range test results for sodium and magnesium
TABLE 7 data of linear equations for sodium and magnesium
It can be seen that the linearity of the sodium element and the magnesium element is good, and the linear correlation coefficient is more than 0.995, which meets the requirements. As the linear equations of the sodium element and the magnesium element both zero, and the correlation coefficient is more than or equal to 0.995, the linear ranges of the sodium element and the magnesium element are respectively 0 mg/L-2.0 mg/L and 0 mg/L-1.0 mg/L.
2) Detection limit and quantitative limit test: and (3) testing the solution to be tested according to the method provided by the invention, continuously measuring the sample solution for 7 times, and measuring, analyzing and recording the response values of the sodium element and the magnesium element by ICP-MS. Continuously measuring the 3-time standard deviation (3SD) of the strength of the test solution as a detection limit; the limit of quantitation was 10 times the standard deviation (10SD) of the strength of the test solution measured continuously. Linear equation calculation was performed, and the LOD & LOQ concentrations of sodium and magnesium were obtained, and the results are shown in table 8.
TABLE 8 analysis of detection limit and quantitation limit test results for sodium and magnesium
The method aims at the detection limit of sodium element of 0.230mg/L, the quantification limit of 0.767mg/L and the good linear relation of sodium element in the range of 0 mg/L-2.0 mg/L; the method aims at the detection limit of 0.032mg/L, the quantification limit of 0.107mg/L and the good linear relation of the magnesium element in the range of 0 mg/L-1.0 mg/L.
3) And (3) accuracy test: the samples were tested according to the method of the present invention with the ranges of sodium and magnesium being 50%, 100% and 150% and the recovery rates were determined at different concentrations and are shown in Table 9.
TABLE 9 accuracy (recovery rate) test results (%)
The result shows that the recovery rate of the sodium element with 50 percent standard addition is between 81.3 percent and 109.4 percent; the recovery rate of sodium element with 100 percent standard addition is between 78.6 percent and 93.0 percent; the recovery rate of sodium element with 150% standard addition is 93.8% -124.7%. The recovery rate of the magnesium element with 50 percent standard addition is between 89.8 percent and 121.4 percent; the recovery rate of the magnesium element with 100 percent standard addition is between 86.3 percent and 97.9 percent; the recovery rate of 150 percent of magnesium element by adding standard is between 102.4 percent and 121.4 percent. The recovery rate of sodium element and magnesium element at each marking point is 70-150%, and the RSD of each group of 3 parallel samples is less than or equal to 15%, which shows that the method has good accuracy.
4) And (3) repeatability test: the process blank solution and the sample spiking solutions were tested with the ranges for sodium and magnesium spiking being 50%, 100%, 150%, and the results are shown in Table 10.
TABLE 10 repeatability test results (mg/L) for sodium and magnesium elements
The RSD of the sodium element and the magnesium element at each marking point is not more than 15 percent, and the repeatability of the method meets the requirement.
5) And (3) precision experiment: and adding a standard solution into the sample, wherein the concentration of the sodium element is 1.0mg/L, and the concentration of the magnesium element is 0.5 mg/L. The sample was used to perform an intermediate precision test with the spiked solution, and two tests were performed by different persons on different dates, 6 sets were tested in parallel each time, and the results of the RSD measurements are shown in table 11.
TABLE 11 precision test results (mg/L)
It can be seen that RSD of sodium element and magnesium element in the data of two times of tests is not more than 15%, RSD of 12 groups of data of two times of tests is not more than 20%, and the precision test result meets the requirement.
Example 2
Embodiment 2 provides a method for analyzing elements in a lamivudine preparation, comprising the following steps:
(1) preparation of a sample to be tested: adding acid into lamivudine tablets to be detected to dissolve, clear up and fix the volume to obtain liquid to be detected;
(2) preparing a sample labeling solution: adding acid into lamivudine tablets to be detected and sodium element and magnesium element standard mother liquor for dissolving, digesting and fixing volume to obtain a sample standard solution;
(3) inductively coupled plasma mass spectrometry: detecting and analyzing the standard solution and the sample solution by using an inductively coupled plasma mass spectrometer;
(4) and (4) analyzing results: and (5) standard curve drawing and method verification.
Example 2 differs from the embodiment of example 1 in that the acid used for digestion is concentrated nitric acid (i.e., no mixed acid is used).
Example 3
Embodiment 3 provides a method for analyzing elements in a lamivudine preparation, comprising the steps of:
(1) preparation of a sample to be tested: taking a lamivudine tablet to be detected, adding mixed acid for dissolving, digesting and fixing the volume to obtain a liquid to be detected;
(2) preparing a sample labeling solution: taking the lamivudine tablet to be measured and the sodium element and magnesium element standard mother liquor, adding mixed acid for dissolving, digesting and fixing volume to obtain a sample standard solution;
(3) inductively coupled plasma mass spectrometry: detecting and analyzing the standard solution and the sample solution by using an inductively coupled plasma mass spectrometer;
(4) and (4) analyzing results: and (5) standard curve drawing and method verification.
Example 3 differs from the embodiment of example 1 in that the mixed acid used for digestion is concentrated nitric acid: hydrofluoric acid 3 mL: 2mL (i.e., without perchloric acid).
Example 4
Embodiment 4 provides a method for analyzing elements in a lamivudine preparation, comprising the steps of:
(1) preparation of a sample to be tested: taking a lamivudine tablet to be detected, adding mixed acid for dissolving, digesting and fixing the volume to obtain a liquid to be detected;
(2) preparing a sample labeling solution: taking the lamivudine tablet to be measured and the sodium element and magnesium element standard mother liquor, adding mixed acid for dissolving, digesting and fixing volume to obtain a sample standard solution;
(3) inductively coupled plasma mass spectrometry: detecting and analyzing the standard solution and the sample solution by using an inductively coupled plasma mass spectrometer;
(4) and (4) analyzing results: and (5) standard curve drawing and method verification.
Example 4 differs from the embodiment of example 1 in that microwave digestion and acid-chasing operations were not performed after graphite oven digestion.
Example 5
Embodiment 5 provides a method for analyzing elements in a lamivudine preparation, comprising the steps of:
(1) preparation of a sample to be tested: taking a lamivudine tablet to be detected, adding mixed acid for dissolving, digesting and fixing the volume to obtain a liquid to be detected;
(2) preparing a sample labeling solution: taking the lamivudine tablet to be measured and the sodium element and magnesium element standard mother liquor, adding mixed acid for dissolving, digesting and fixing volume to obtain a sample standard solution;
(3) inductively coupled plasma mass spectrometry: detecting and analyzing the standard solution and the sample solution by using an inductively coupled plasma mass spectrometer;
(4) and (4) analyzing results: and (5) standard curve drawing and method verification.
Example 5 differs from the embodiment of example 1 in that no acid-scavenging operation is performed after microwave digestion.
Example 6
Embodiment 6 provides a method for analyzing elements in a lamivudine preparation, comprising the steps of:
(1) preparation of a sample to be tested: taking a lamivudine tablet to be detected, adding mixed acid for dissolving, digesting and fixing the volume to obtain a liquid to be detected;
(2) preparing a sample labeling solution: taking the lamivudine tablet to be measured and the sodium element and magnesium element standard mother liquor, adding mixed acid for dissolving, digesting and fixing volume to obtain a sample standard solution;
(3) inductively coupled plasma mass spectrometry: detecting and analyzing the standard solution and the sample solution by using an inductively coupled plasma mass spectrometer;
(4) and (4) analyzing results: and (5) standard curve drawing and method verification.
Example 6 differs from the embodiment of example 1 in that the flow rate of the auxiliary gas was 0.10L/min under the ICP-MS test conditions.
Example 7
Embodiment 7 provides a method for analyzing elements in a lamivudine preparation, comprising the steps of:
(1) preparation of a sample to be tested: taking a lamivudine tablet to be detected, adding mixed acid for dissolving, digesting and fixing the volume to obtain a liquid to be detected;
(2) preparing a sample labeling solution: taking the lamivudine tablet to be measured and the sodium element and magnesium element standard mother liquor, adding mixed acid for dissolving, digesting and fixing volume to obtain a sample standard solution;
(3) inductively coupled plasma mass spectrometry: detecting and analyzing the standard solution and the sample solution by using an inductively coupled plasma mass spectrometer;
(4) and (4) analyzing results: and (5) standard curve drawing and method verification.
Example 7 differs from the embodiment of example 1 in that the atomizing gas flow rate in the ICP-MS test conditions was 0.40L/min.
Example 8
Embodiment 8 provides a method for analyzing elements in a lamivudine preparation, comprising the steps of:
(1) preparation of a sample to be tested: taking a lamivudine tablet to be detected, adding mixed acid for dissolving, digesting and fixing the volume to obtain a liquid to be detected;
(2) preparing a sample labeling solution: taking the lamivudine tablet to be measured and the sodium element and magnesium element standard mother liquor, adding mixed acid for dissolving, digesting and fixing volume to obtain a sample standard solution;
(3) inductively coupled plasma mass spectrometry: detecting and analyzing the standard solution and the sample solution by using an inductively coupled plasma mass spectrometer;
(4) and (4) analyzing results: and (5) standard curve drawing and method verification.
Example 8 differs from the embodiment of example 1 in that the lamivudine tablet does not contain a silica component.
Test results
The results analyses described in example 1, including standard curve plotting, limit of quantitation test, accuracy test, reproducibility test and precision test, were performed on examples 2 to 8, and 0.5mg/L thereof, the limit of quantitation at 100% (accuracy test) and RSD value (reproducibility test) were given as shown in Table 12.
TABLE 12 test results of examples 2 to 8
The test results show that the test method provided by the invention has the advantages of high sensitivity, low detection limit and good reproducibility, and can accurately and precisely determine the sodium and magnesium elements in the specific lamivudine by combining with a chemical pretreatment means. The method selects proper element isotopes for determination according to the selection of high abundance and small interference, and has the advantages of high determination speed, high accuracy and good precision under the conditions of eliminating matrix interference and mass spectrum interference.
The above description is only a preferred embodiment of the present invention, and is not intended to limit the present invention in other forms, and any person skilled in the art may modify or change the technical content of the above disclosure into equivalent embodiments with equivalent changes, but all those simple modifications, equivalent changes and modifications made to the above embodiments according to the technical spirit of the present invention still belong to the protection scope of the present invention.
Claims (3)
1. A method for analyzing elements in lamivudine preparation is characterized by comprising the following steps: (1) preparation of a sample to be tested: taking a lamivudine tablet to be detected, adding mixed acid for dissolving, digesting and fixing the volume to obtain a liquid to be detected; (2) preparing a sample labeling solution: taking the lamivudine tablet to be measured and the sodium element and magnesium element standard mother liquor, adding mixed acid for dissolving, digesting and fixing volume to obtain a sample standard solution; (3) inductively coupled plasma mass spectrometry: detecting and analyzing the standard solution and the sample solution by using an inductively coupled plasma mass spectrometer; (4) and (4) analyzing results: drawing a standard curve and verifying the method;
the lamivudine tablet to be detected contains silicon dioxide component, and the content of the silicon dioxide accounts for 0.05-2wt% of the lamivudine tablet;
the preparation process of the sample to be detected comprises the following steps: adding 5ml of mixed acid into a beaker of lamivudine to be detected, digesting at a certain temperature by using a graphite furnace, continuing to digest by using microwaves and driving up the acid, cooling to room temperature, transferring to a 50ml volumetric flask, adding water to a constant volume to scale, and shaking up for later use; transferring a volumetric flask with the volume of 0.1ml to 10ml of the solution, fixing the volume to the scale with 2% nitric acid, shaking up, and preparing three parts in parallel to obtain the product;
the digestion temperature is 115-125 ℃;
the mixed acid is concentrated nitric acid, hydrofluoric acid and perchloric acid, wherein the mixed acid is prepared from the following components in parts by weight: hydrofluoric acid: the volume ratio of perchloric acid is 2: 2: 1; the test conditions included: output power of high frequency generator: 1200W; plasma gas flow rate: 18L/min; flow rate of auxiliary gas: 1.2L/min; flow rate of the atomizer: 0.83L/min.
2. The analytical method of claim 1, wherein the elements to be analyzed are sodium and magnesium.
3. The assay of claim 2, wherein the test concentration of elemental sodium is in the range of 0.1 to 2.0 mg/L; the test range of the magnesium element is 0.05-1.0 mg/L.
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