CN110988105A - Analysis method for determining hydromorphone hydrochloride raw material medicine element impurities - Google Patents
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Abstract
The invention relates to an analysis method for determining hydromorphone hydrochloride raw material medicine element impurities. The method comprises the steps of system applicability, standard curve preparation, internal standard solution preparation, sample preparation and preparation of a standard-added recovery sample; drawing a standard curve, detecting a limit, detecting a sample and detecting the recovery rate of the added standard. The invention reduces the acid-dispelling temperature by simultaneously measuring and splitting 7 elements into 6 metal elements of arsenic, cadmium, lead, cobalt, nickel and vanadium and independently measuring the mercury (Hg) element, solves the problem that the recovery rate of the mercury element does not reach the standard by reducing the universal temperature from 150 ℃ to 130 ℃, can improve the recovery rate to about 90 percent, and can reduce the interference of the mercury (Hg) element on other elements due to strong memory effect by independently measuring. By selecting germanium, indium, bismuth and scandium internal standards, the influence of signal drift and matrix effect on measurement can be effectively reduced.
Description
Technical Field
The invention belongs to the technical field of analysis of hydromorphone hydrochloride elemental impurities, and particularly relates to an analysis method for determining hydromorphone hydrochloride bulk drug elemental impurities.
Background
Various methods for measuring element impurities are recorded in the general rules of the four departments of the Chinese pharmacopoeia, and the methods have different characteristics and certain applicability. Including but not limited to atomic absorption spectrophotometry, inductively coupled plasma mass spectrometry (ICP-MS), etc. ICP-MS is a mass spectrum type element analysis method using plasma as an ion source. The method is mainly used for simultaneously measuring various elements, during measurement, a sample is introduced into an atomization system by carrier gas (argon) to be atomized, then enters a plasma central area in the form of aerosol, is desolvated, vaporized and dissociated and ionized in high-temperature and inert atmosphere, is converted into positive ions with positive charges, enters a mass spectrometer through an ion collection system, is separated by the mass spectrometer according to mass-to-charge ratio, and is used for measuring the content of corresponding elements in the sample according to the peak intensity of an element mass spectrum.
The existing impurity detection method comprises the following steps:
ICH, FDA, USP, CFDA regulations on elemental impurities
2. Determination of inorganic element impurities and limits in pharmaceutical products
3. Elemental impurity risk assessment method
4. ICP detection method for inorganic element impurities
5. Detecting inorganic element impurity by USP <233> method
Validation of USP <233> methodology and validation of self-research methods
7. Examples analysis detection of inorganic element impurities and validation of methodology
Hydromorphone hydrochloride is an opioid receptor agonist, belongs to a class of tube pharmaceuticals, and mainly comprises hydromorphone hydrochloride with the chemical name of 4,5 α -epoxy-3-hydroxy-17-methyl morphinan-6-one hydrochloride.
Chemical structural formula:
the molecular formula is as follows: c17H19NO3·HCl
Molecular weight: 321.8
The prior art does not develop and research an element impurity analysis method of a hydromorphone hydrochloride raw material medicine.
Disclosure of Invention
The invention aims to provide an analysis method for determining hydromorphone hydrochloride raw material medicine element impurities. The method is used for determining the element impurities in the hydromorphone hydrochloride bulk drug by inductively coupled plasma mass spectrometry. The method confirms whether element limits in the hydromorphone hydrochloride bulk drug meet requirements specified by an ICH Q3D guiding principle through experimental detection, and combines the characteristics of the hydromorphone hydrochloride bulk drug, the types and content levels of elements to be detected and the limit control of instrument and equipment conditions in a laboratory as a solution. The authenticity of the data of the detection sample determined by the invention is verified by the good recovery rate of each metal element.
The technical scheme adopted by the invention is as follows:
an analytical method for determining hydromorphone hydrochloride bulk drug elemental impurities, the method comprising the steps of:
s1 system applicability: analyzing the NexION tuning solution by using a method STD Performance Check detection and optimizing main instrument parameters of an ICP-MS (inductively coupled plasma mass spectrometry) instrument;
preparing a standard curve and drawing the standard curve by S2;
preparation of internal standard solution of S3: respectively taking 1mL of a germanium single element standard solution (Ge:1000 mug/mL), an indium single element standard solution (In:1000 mug/mL), a bismuth single element standard solution (Bi:1000 mug/mL) and a scandium single element standard solution (Sc:1000 mug/mL) to the same volumetric flask with 100mL scales, adding ultrapure water for dilution, fixing the volume to the scales, and shaking up; and precisely measuring the solution in a volumetric flask with scales of 1mL to 100mL, adding ultrapure water for dilution, fixing the volume to the scales, and shaking up to obtain the product.
S4 sample preparation:
weighing about 0.2g of sample, placing the sample in a polytetrafluoroethylene digestion tank, adding 8mL of nitric acid, sealing, cooling digestion liquid to be below 80 ℃ after microwave digestion is completed, taking out the digestion tank, cooling, washing the digestion liquid into a volumetric flask with 50mL scales by using a diluent, adding 200 mu L of gold standard solution (10 mu g/mL), adding the diluent for dilution, fixing the volume to 50mL scales, and shaking up;
s5 preparation of recovery sample with standard addition: weighing about 0.2g of sample, placing the sample in a polytetrafluoroethylene digestion tank, respectively adding 1.25mL of lead stock solution I (Pb:4 mug/mL), 1mL of cadmium stock solution I (Cd:2 mug/mL), 3mL of arsenic stock solution I (As:5 mug/mL), 1.25mL of cobalt stock solution I (Co:4 mug/mL), 5mL of nickel stock solution I (Ni:4 mug/mL) and 2.5mL of vanadium stock solution I (V:4 mug/mL), adding 8mL of nitric acid, sealing, cooling the digestion solution to below 80 ℃ after microwave is completed, taking out the digestion tank, cooling, washing the digestion solution into a 50mL graduated volumetric flask by using a diluent, adding 200 mug/mL of gold standard solution (10 mug/mL), diluting with the diluent, diluting to a constant volume, shaking up to 50mL graduation, and uniformly stirring;
drawing a standard curve of S6, detecting limit, detecting a sample and detecting the recovery rate of the added standard: under the optimal state of the instrument, an internal Standard sample feeding tube of the instrument is always inserted into an internal Standard solution in the instrument analysis work, and a blank solution, a Standard1, a Standard2, a Standard3, a Standard4, a Standard5, an 11-time blank solution, a sample solution and 6 parts of Standard-added recovery solution are sequentially added for detection and calculation;
and completing the analysis of the hydromorphone hydrochloride raw material medicine element impurities.
Preferably, in the step S1, the ICP-MS (inductively coupled plasma mass spectrometry) instrument has the following main working parameters:
RF power of 1550W, RF matching of 1.67V, S/C temperature of 2 ℃ in the atomization chamber, Smpl Depth of 5mm, Cool flow of 14L/min, Auxiliary flow of 0.8L/min and Nebulizer flow of 0.96L/min.
Preferably, the instrument parameter acceptance criteria of step S1 are:
Intensity Criterion:Be 9>4500；
Intensity Criterion:In 115>80000；
Intensity Criterion:U 238>60000；
Intensity Criterion:Bkgd 220≤3；
Formula Criterion:CeO 156/Ce 140≤0.025；
Formula Criterion:Ce++70/Ce 140≤0.03。
preferably, in the step S2, in the preparation of the standard curve and the drawing of the standard curve: precisely measuring 0.1mL,0.2mL,0.4mL,0.8mL and 1.6mL of lead stock solution (Pb:100ng/mL) respectively; accurately measuring 0.1mL,0.2mL,0.4mL,0.8mL and 1.6mL of cadmium stock solution (Cd:50ng/mL) respectively; accurately measuring 0.1mL,0.2mL,0.4mL,0.8mL and 1.0mL of arsenic stock solution (As:100ng/mL) respectively; accurately measuring 0.1mL,0.2mL,0.4mL,0.8mL and 1.0mL of mercury stock solution (20ng/mL) respectively; precisely measuring 0.1mL,0.2mL,0.4mL,0.8mL and 1.6mL of cobalt stock solution (Co:100ng/mL) respectively; precisely measuring 0.1mL,0.2mL,0.4mL,0.8mL and 1.0mL of nickel stock solution (Ni:200ng/mL) respectively; precisely measuring 0.1mL,0.2mL,0.4mL,0.8mL and 1.0mL of vanadium stock solution (V:200ng/mL) respectively; the stock solutions with different gradient volumes are respectively placed in 5 volumetric flasks with 10mL scales in a one-to-one correspondence manner, 200 mu L of gold standard solution (10 mu g/mL) is added, then a diluent is added for dilution, the scales are determined, the concentration is shown in the following table 1, and new formula is used.
Preferably, in the steps S4 and S5, the microwave digestion procedure is as follows:
the microwave digestion program for measuring six elements of arsenic (As), cadmium (Cd), lead (Pb), cobalt (Co), nickel (Ni) and vanadium (V) is As follows: maintaining at 120 deg.C and 20atm for 5min, 150 deg.C and 25atm for 5min, 180 deg.C and 30atm for 5min, and 210 deg.C and 40atm for 20 min.
The microwave digestion procedure for measuring mercury (Hg) element is as follows: maintaining at 120 deg.C and 20atm for 5min, at 130 deg.C and 25atm for 5min, at 180 deg.C and 30atm for 5min, and at 210 deg.C and 40atm for 20 min.
Preferably, in step S6: testing blank solution, continuously injecting sample for 11 times, dividing 3 times standard deviation of the measured value of the blank control solution by the slope of the standard curve of corresponding element, and detecting each element as a limit: 9.196ng/mL of As; cd 1.148ng/mL; co 2.118 ng/mL; hg 12.389 ng/mL; ni 66.346 ng/mL; pb 22.045 ng/mL; V2.086ng/mL.
The invention has the following beneficial effects:
1. according to the guiding principles of USP232/233 and ICHO3D, the risk assessment of the administration route is carried out on 7 kinds of metal element impurities of class 1 elements of arsenic (As), cadmium (Cd), mercury (Hg) and lead (Pb) and class 2A cobalt (Co), nickel (Ni), vanadium (V) and the like, and a set of complete analysis method verification is established for the element impurities of hydromorphone hydrochloride. Particularly, 6 metal elements of arsenic (As), cadmium (Cd), lead (Pb), cobalt (Co), nickel (Ni) and vanadium (V) are simultaneously measured and split into 7 elements and mercury (Hg) is separately measured, so that the acid removing temperature is reduced, the problem that the recovery rate of the mercury (Hg) is not up to standard is solved by reducing the universal temperature of 150 ℃ to 130 ℃, the recovery rate can be improved to about 90 percent, and the interference of the mercury (Hg) due to strong memory effect on other elements can be reduced by separately measuring.
2. The internal standards of germanium (Ge), indium (In), bismuth (Bi) and scandium (Sc) are selected, so that the influence of signal drift and matrix effect on measurement can be effectively reduced.
3. The recovery rate of each element concentration in the standard sample is between 80 and 120 percent. The average recovery rates of 7 elements of arsenic (As), cadmium (Cd), lead (Pb), cobalt (Co), nickel (Ni), vanadium (V) and mercury (Hg) after 6 times of determination are respectively As follows: 98.2%, 97.1%, 99.6%, 94.4%, 102.3%, 97.1%, 91.7%. The data authenticity of the detection sample determined by the invention is verified by showing good recovery rate of each metal element. Easy operation, short time, high sensitivity and reliable detection data.
The specific implementation mode is as follows:
example 1
An analytical method for determining hydromorphone hydrochloride bulk drug elemental impurities, the method comprising the steps of:
1. diluent preparation (2% nitric acid solution-2% hydrochloric acid solution): precisely measuring 1mL of electronic pure grade nitric acid, and using ultrapure water to fix the volume to 500 mL; then precisely measuring 1mL of electronic pure grade hydrochloric acid, and metering the volume to a 500mL volumetric flask (the material of the volumetric flask is polyethylene terephthalate (PET), the same below) by using ultrapure water. And uniformly mixing the two solutions in a ratio of 1: 1.
2. Gold standard solution preparation (10. mu.g/mL): 0.5mL of gold single element standard solution (1000 mug/mL) is transferred into a volumetric flask with 50mL scales (the manufacturer is the national analysis and test center for nonferrous metals and electronic materials, and the manufacturer is the same below) and diluted with ultrapure water, and the volume is fixed to 50mL scales, and the solution is shaken up.
3. Standard solution stock (Pb:100ng/mL, Cd:50ng/mL, As:100ng/mL, Hg:20ng/mL, Co:100ng/mL, Ni:200ng/mL, V:200ng/mL) preparation:
3.1 transferring 1mL of lead single element standard solution (100 mu g/mL), adding a diluent for dilution, diluting to a constant volume of 25mL, and shaking up to obtain a lead stock solution I (Pb:4 mu g/mL); and then 0.25mL of the solution is taken, diluted by a diluent, and the volume is determined to 10mL, and the solution is shaken up to obtain the lead stock solution II (Pb:100 ng/mL).
3.2 transferring 0.25mL of cadmium single element standard solution (100 mug/mL), adding a diluent for dilution, diluting to 25mL of volume, and shaking up to obtain cadmium stock solution I (Cd:2 mug/mL); and then 0.25mL of the solution is taken, diluted by a diluent, and the volume is determined to 10mL, and the solution is shaken up to obtain the cadmium stock solution II (Cd:50 ng/mL).
3.3 transferring 2.5mL of arsenic single element standard solution (100 mu g/mL), adding a diluent for diluting, diluting to 50mL of volume, and shaking up to obtain arsenic stock solution I (As:5 mu g/mL); and then 0.2mL of the solution is taken, diluted by a diluent, and the volume is determined to 10mL, and the solution is shaken up to obtain an arsenic stock solution II (As:100 ng/mL).
3.4 transferring 1mL of mercury single element standard solution (100 mug/mL), adding a diluent for dilution, diluting to a constant volume of 25mL, and shaking up to obtain mercury stock solution I (Hg:4 mug/mL); and then 0.25mL of the solution is taken, diluted by a diluent, and the volume is determined to 50mL, and the solution is shaken up to obtain the mercury stock solution II (Hg:20 ng/mL).
3.5 transferring 0.4mL of cobalt single element standard solution (1000 mug/mL), adding a diluent for dilution, diluting to 100mL of volume, and shaking up to obtain cobalt stock solution I (Co:4 mug/mL); and then 0.25mL of the solution is taken, diluted by a diluent, and the volume is determined to 10mL, and the solution is shaken up to obtain a cobalt stock solution II (Co:100 ng/mL).
3.6 transferring 0.4mL of nickel single element standard solution (1000 mug/mL), adding a diluent for dilution, diluting to 100mL of volume, and shaking up to obtain nickel stock solution I (Ni:4 mug/mL); and then 0.5mL of the solution is taken, diluted by a diluent, and the volume is determined to 10mL, and the solution is shaken up to obtain a nickel stock solution II (Ni:200 ng/mL).
3.7 transferring 0.4mL of vanadium single element standard solution (1000 mug/mL), adding a diluent for dilution, diluting to 100mL of volume, and shaking up to obtain vanadium stock solution I (V:4 mug/mL); and then 0.5mL of the solution is taken, diluted by a diluent, and the volume is determined to 10mL, and the solution is shaken up to obtain vanadium stock solution II (V:200 ng/mL).
4. Preparation of a standard curve: precisely measuring 0.1mL,0.2mL,0.4mL,0.8mL and 1.6mL of lead stock solution (Pb:100ng/mL) respectively; accurately measuring 0.1mL,0.2mL,0.4mL,0.8mL and 1.6mL of cadmium stock solution (Cd:50ng/mL) respectively; accurately measuring 0.1mL,0.2mL,0.4mL,0.8mL and 1.0mL of arsenic stock solution (As:100ng/mL) respectively; accurately measuring 0.1mL,0.2mL,0.4mL,0.8mL and 1.0mL of mercury stock solution (20ng/mL) respectively; precisely measuring 0.1mL,0.2mL,0.4mL,0.8mL and 1.6mL of cobalt stock solution (Co:100ng/mL) respectively; precisely measuring 0.1mL,0.2mL,0.4mL,0.8mL and 1.0mL of nickel stock solution (Ni:200ng/mL) respectively; precisely measuring 0.1mL,0.2mL,0.4mL,0.8mL and 1.0mL of vanadium stock solution (V:200ng/mL) respectively; the stock solutions with different gradient volumes are respectively put into 5 volumetric flasks with 10mL scales in a one-to-one correspondence manner, 200 mu L of gold standard solution (10 mu g/mL) is added, and then diluent is added for dilution and the scales are fixed. The concentrations are shown in the table below, with new formulations.
TABLE 1
5. Preparing an internal standard solution: respectively precisely measuring 1mL of a germanium single element standard solution (Ge:1000 mug/mL), an indium single element standard solution (In:1000 mug/mL), a bismuth single element standard solution (Bi:1000 mug/mL) and a scandium single element standard solution (Sc:1000 mug/mL) In a volumetric flask with the same 100mL scale, adding ultrapure water for dilution, fixing the volume to the scale, and shaking up; and precisely measuring the solution in a volumetric flask with scales of 1mL to 100mL, adding ultrapure water for dilution, fixing the volume to the scales, and shaking up to obtain the product.
6. Sample preparation: weighing about 0.2g of sample, placing the sample in a polytetrafluoroethylene digestion tank, adding 8mL of nitric acid, sealing, carrying out microwave digestion by a temperature-rising program (keeping the temperature at 120 ℃ for 5min, keeping the temperature at 150 ℃ for 5min, keeping the temperature at 180 ℃ for 5min, keeping the temperature at 210 ℃ for 20 min), cooling the digestion solution to below 80 ℃, taking out the digestion tank, measuring six elements of arsenic (As), cadmium (Cd), lead (Pb), cobalt (Co), nickel (Ni) and vanadium (V), removing acid to 1mL (soybean grain size) at 150 ℃, removing acid to 1mL (soybean grain size) at 130 ℃ when measuring the element of mercury (Hg), cooling, washing the solution in a 50mL volumetric flask with a small amount of diluent, adding 200 mu L of gold standard solution (10 mu g/mL), diluting with the diluent, fixing the volume to 50mL, and shaking up.
7. Preparing a labeling recovery sample: weighing about 0.2g of sample, placing the sample in a polytetrafluoroethylene digestion tank, respectively adding 1.25mL of lead stock solution I (Pb:4 mug/mL), 1mL of cadmium stock solution I (Cd:2 mug/mL), 3mL of arsenic stock solution I (As:5 mug/mL), 1.25mL of cobalt stock solution I (Co:4 mug/mL), 5mL of nickel stock solution I (Ni:4 mug/mL) and 2.5mL of vanadium stock solution I (V:4 mug/mL), adding 8mL of nitric acid, sealing, keeping the temperature program (120 ℃ for 5min, 150 ℃ for 5min, 180 ℃ for 5min and 210 ℃ for 20 min), after microwave digestion is completed, cooling the digestion solution to below 80 ℃, taking out the digestion tank, measuring the size of 150 ℃ bean acid to 1mL when six elements of arsenic (As), cadmium (Cd), lead (Pb) cobalt (Co), nickel (Ni) and vanadium (V) are used, measuring the size of bean acid to 1mL when mercury (Hg) is used, measuring the size of yellow bean acid to 1mL, the mixture is cooled, washed into a volumetric flask with 50mL scales by using a small amount of diluent, added with 200 mu L of gold standard solution (10 mu g/mL), diluted by adding the diluent, and shaken up until the volume is up to 50mL scales.
8. The inductively coupled plasma mass spectrometer ICP-MS has the following main working parameters:
8.1 RF power: 1550W
8.2 RF matching (radio frequency voltage): 1.67V
8.3S/C temperature (nebulization chamber temperature): 2 deg.C
8.4 Smpl Depth (sampling Depth): 5mm
8.5 Cool flow (cooling gas flow rate): 14L/min
8.6 Auxilliary flow (auxiliary gas flow rate): 0.8L/min
8.7 Nebulizer flow (atomization gas flow rate): 0.96L/min
9. Drawing a standard curve, detecting limit, detecting a sample and detecting the recovery rate of added standard: the internal Standard sample introduction tube of the instrument was inserted into the internal Standard solution all the time during the instrument analysis under the optimal condition, and the Blank solution (Blank solution Blank), Standard1, Standard2, Standard3, Standard4, Standard5, 11 times of Blank solution (kb1-kb11), sample solution (QM161201 ) and 6 parallel taggant recovery solutions (taggant recovery solution 1QM161201-astd1, taggant recovery solution 2QM161201-astd2, taggant recovery solution 3QM161201-astd3, taggant recovery solution 4QM161201-astd4, taggant recovery solution 5QM161201-astd5 and taggant recovery solution 6QM161201-astd6) were sequentially introduced.
TABLE 2 detection data of six elements arsenic (As), cadmium (Cd), lead (Pb), cobalt (Co), nickel (Ni) and vanadium (V)
TABLE 3 Mercury (Hg) elemental detection data
10. The result of the detection
10.1 linear correlation coefficients of 7 element impurities of arsenic (As), cadmium (Cd), lead (Pb), cobalt (Co), nickel (Ni), vanadium (V) and mercury (Hg) can reach above 0.999
10.2 and combining the standard curve result to carry out quantitative analysis on the content of 7 elements of the sample, namely, hydromorphone hydrochloride arsenic (As), cadmium (Cd), lead (Pb), cobalt (Co), nickel (Ni), vanadium (V) and mercury (Hg), which are all less than the detection limit, and judging that the content is not detected. The standard regulation that arsenic (As) in hydromorphone hydrochloride can not exceed 1.5 mu g/g, cadmium (Cd) can not exceed 0.2 mu g/g, lead (Pb) can not exceed 0.5 mu g/g, cobalt (Co) can not exceed 0.5 mu g/g, nickel (Ni) can not exceed 2 mu g/g, vanadium (V) can not exceed 1 mu g/g and mercury (Hg) can not exceed 0.3 mu g/g is calculated according to the administration route and daily exposure (PDE) specified in the ICH Q3D guideline.
10.3 arsenic (As), cadmium (Cd), lead (Pb), cobalt (Co), nickel (Ni), vanadium (V), mercury (Hg)7 kinds of elemental detection limits according to getting the blank solution to test, sample introduction 11 times continuously, calculate the detection limit of this method with 3 times standard deviation of blank reference solution measured value divided by the slope of the corresponding elemental standard curve, the calculated result is respectively: 9.196ng/mL, 1.148ng/mL, 22.045ng/mL, 2.118ng/mL, 66.346ng/mL, 2.086ng/mL, 12.389 ng/mL.
10.4 the average recovery rates of 7 elements of arsenic (As), cadmium (Cd), lead (Pb), cobalt (Co), nickel (Ni), vanadium (V) and mercury (Hg) after 6 times of determination are respectively As follows: 98.2%, 97.1%, 99.6%, 94.4%, 102.3%, 97.1%, 91.7%.
Comparative example 1
In example 1, 7 elements of arsenic (As), cadmium (Cd), lead (Pb), cobalt (Co), nickel (Ni), vanadium (V), and mercury (Hg) were simultaneously detected.
7 elements of arsenic (As), cadmium (Cd), lead (Pb), cobalt (Co), nickel (Ni), vanadium (V) and mercury (Hg) are simultaneously measured, and the microwave digestion and acid-dispelling temperature is the universal measurement result at 150 ℃. The rest is the same as in example 1. The results are shown in Table 4. The recovery rate of mercury (Hg) by the method is only 73.5%.
TABLE 4
Comparative example 2
The four internal standard elements of germanium (Ge), indium (In), bismuth (Bi) and scandium (Sc) can be selected from 7 internal standard elements of germanium (Ge), indium (In), bismuth (Bi), scandium (Sc), titanium (Ti), gallium (Ga) and thallium (Tl) which can be selected to effectively reduce the influence of signal drift and matrix effect on the determination.
For example: when four internal standard elements of titanium (Ti), gallium (Ga), indium (In) and thallium (Tl) are selected, the signal of the titanium (Ti) is shifted to 133.0 percent, and the signal of the thallium (Tl) is shifted to 150.1 percent. Otherwise, the same method As that of example 1 was adopted to detect the recovery rate of arsenic (As) of only 81.6% and the recovery rate of mercury (Hg) of only 69.5%. The results are shown in Table 5.
TABLE 5
Claims (9)
1. An analysis method for determining hydromorphone hydrochloride raw material medicine element impurities is characterized by comprising the following steps:
s1 system applicability: analyzing the NexION tuning solution by using a method STD Performance Check detection and optimizing main instrument parameters of an inductively coupled plasma mass spectrometer;
preparing a standard curve and drawing the standard curve by S2;
preparation of internal standard solution of S3: respectively taking standard solutions of germanium single elements, indium single elements, bismuth single elements and scandium single elements for dilution and volume fixing;
s4 sample preparation: weighing a sample, placing the sample in a polytetrafluoroethylene digestion tank, adding nitric acid, sealing, cooling digestion liquid after microwave digestion is complete, taking out the digestion tank, cooling, washing the digestion tank into a volumetric flask by using a diluent, adding a gold standard solution, adding the diluent for dilution, fixing the volume and shaking up;
s5 preparation of recovery sample with standard addition: weighing a sample, placing the sample in a polytetrafluoroethylene digestion tank, respectively adding a lead stock solution I, a cadmium stock solution I, an arsenic stock solution I, a cobalt stock solution I, a nickel stock solution I and a vanadium stock solution I, adding nitric acid, sealing, completely digesting by microwave, cooling a digestion solution, taking out the digestion tank, cooling, washing the digestion tank into a graduated volumetric flask by using a diluent, adding a gold standard solution, adding the diluent for diluting and fixing the volume, and shaking up;
drawing a standard curve of S6, detecting limit, detecting a sample and detecting the recovery rate of the added standard: under the optimal state of the instrument, an internal Standard sample feeding tube of the instrument is always inserted into an internal Standard solution in the instrument analysis work, and a blank solution, a Standard1, a Standard2, a Standard3, a Standard4, a Standard5, an 11-time blank solution, a sample solution and 6 parts of Standard-added recovery solution are sequentially added for detection and calculation;
and completing the analysis of the hydromorphone hydrochloride raw material medicine element impurities.
2. The method according to claim 1, wherein the inductively coupled plasma mass spectrometer of step S1 has the following main operating parameters: the radio frequency power is 1550W, the radio frequency voltage is 1.67V, the temperature of the atomizing chamber is 2 ℃, the sampling depth is 5mm, the cooling air flow rate is 14L/min, the auxiliary air flow rate is 0.8L/min, and the atomizing air flow rate is 0.96L/min.
3. The method as claimed in claim 1, wherein the step S1 is implemented by using the instrument parameter acceptance criteria as follows:
Intensity Criterion:Be 9>4500；
Intensity Criterion:In 115>80000；
Intensity Criterion:U 238>60000；
Intensity Criterion:Bkgd 220≤3；
Formula Criterion:CeO 156/Ce 140≤0.025；
Formula Criterion:Ce++70/Ce 140≤0.03。
4. the method of claim 1,
in the step S2 of preparing the standard curve and drawing the standard curve: precisely measuring 0.1mL,0.2mL,0.4mL,0.8mL and 1.6mL of lead stock solution respectively, wherein the concentration of the lead stock solution is 100 ng/mL; accurately measuring 0.1mL,0.2mL,0.4mL,0.8mL and 1.6mL of cadmium stock solution respectively, wherein the concentration of the cadmium stock solution is 50 ng/mL; accurately measuring 0.1mL,0.2mL,0.4mL,0.8mL and 1.0mL of arsenic stock solution respectively, wherein the concentration of the arsenic stock solution is 100 ng/mL; accurately measuring 0.1mL,0.2mL,0.4mL,0.8mL and 1.0mL of mercury stock solution respectively, wherein the concentration of the mercury stock solution is 20 ng/mL; accurately measuring 0.1mL,0.2mL,0.4mL,0.8mL and 1.6mL of cobalt stock solution respectively, wherein the concentration of the cobalt stock solution is 100 ng/mL; precisely measuring 0.1mL,0.2mL,0.4mL,0.8mL and 1.0mL of nickel stock solution respectively, wherein the concentration of the nickel stock solution is 200 ng/mL; respectively and precisely measuring 0.1mL,0.2mL,0.4mL,0.8mL and 1.0mL of vanadium stock solution, wherein the concentration of the vanadium stock solution is 200 ng/mL; and (3) correspondingly placing the stock solutions with different gradient volumes into 5 volumetric flasks with scales of 10mL, adding 200 mu L of 10 mu g/mL gold standard solution, diluting with a diluent, and fixing the scales.
5. The method according to claim 1, wherein the step S3 is performed by a method comprising: respectively taking 1mL of the germanium single element standard solution, 1mL of the indium single element standard solution, 1mL of the bismuth single element standard solution and 1mL of the scandium single element standard solution to the same volumetric flask with the 100mL scale, adding ultrapure water for dilution, fixing the volume to the scale, and shaking up; and precisely measuring the solution in a volumetric flask with scales of 1mL to 100mL, adding ultrapure water for dilution, fixing the volume to the scales, and shaking up to obtain the product.
6. The method of claim 5, wherein the concentration of the germanium single element standard solution is 1000 μ g/mL, the concentration of the indium single element standard solution is 1000 μ g/mL, the concentration of the bismuth single element standard solution is 1000 μ g/mL, and the concentration of the scandium single element standard solution is 1000 μ g/mL.
7. The method according to claim 1, wherein in the steps S4 and S5, the microwave digestion procedure is as follows:
the microwave digestion program for determining six elements of arsenic, cadmium, lead, cobalt, nickel and vanadium is as follows: maintaining at 120 deg.C and 20atm for 5min, 150 deg.C and 25atm for 5min, 180 deg.C and 30atm for 5min, and 210 deg.C and 40atm for 20 min.
The microwave digestion procedure for measuring mercury element is as follows: maintaining at 120 deg.C and 20atm for 5min, at 130 deg.C and 25atm for 5min, at 180 deg.C and 30atm for 5min, and at 210 deg.C and 40atm for 20 min.
8. The method according to claim 1, wherein in step S5, lead stock solution I is at a concentration of 4 μ g/mL and a volume of 1.25 mL; the concentration of the cadmium stock solution I is 2 mug/mL, and the volume is 1 mL; the concentration of the arsenic stock solution is 5 mug/mL, and the volume is 3 mL; the concentration of the cobalt stock solution is 4 mug/mL, and the volume is 1.25 mL; the concentration of the nickel stock solution is 4 mug/mL, and the volume is 5 mL; the concentration of the vanadium stock solution is 4 mug/mL, and the volume is 2.5 mL.
9. The method according to claim 1, wherein in step S6: testing blank solution, continuously injecting sample for 11 times, dividing 3 times standard deviation of the measured value of the blank control solution by the slope of the standard curve of corresponding element, and detecting each element as a limit: 9.196ng/mL of As; cd1.148 ng/mL; co 2.118 ng/mL; hg 12.389 ng/mL; ni 66.346 ng/mL; pb 22.045 ng/mL; v2.086 ng/mL.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111678972A (en) * | 2020-06-19 | 2020-09-18 | 广州汇标检测技术中心 | Method for detecting impurity elements in bulk drugs |
| CN112326765A (en) * | 2020-10-30 | 2021-02-05 | 淄博高新技术产业开发区生物医药研究院 | Detection method for analyzing content of 24 element impurities in insulin at one time |
| CN114152661A (en) * | 2021-12-02 | 2022-03-08 | 南通联亚药业有限公司 | ICP-MS detection method for element impurities in conjugated estrogen bulk drug containing high-salt matrix |
| CN114487079A (en) * | 2021-12-31 | 2022-05-13 | 乳源东阳光药业有限公司 | Analysis method for measuring elemental impurity silver in rosuvastatin calcium by ICP-MS |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102338770A (en) * | 2010-07-21 | 2012-02-01 | 云南理想药业有限公司 | Method for detecting 14 rare earth elements in Shenshuaining capsules and Xueniao' an capsules |
| US20120178183A1 (en) * | 2011-01-11 | 2012-07-12 | Nolan Garry P | Mass Dots: Nanoparticle Isotope Tags |
| CN105527333A (en) * | 2016-01-25 | 2016-04-27 | 广西壮族自治区环境监测中心站 | Method for determining heavy metal content of sugarcane with electric heating board digestion/ICP-MS (inductively coupled plasma mass spectrometry) methods |
-
2019
- 2019-12-26 CN CN201911370050.8A patent/CN110988105A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102338770A (en) * | 2010-07-21 | 2012-02-01 | 云南理想药业有限公司 | Method for detecting 14 rare earth elements in Shenshuaining capsules and Xueniao' an capsules |
| US20120178183A1 (en) * | 2011-01-11 | 2012-07-12 | Nolan Garry P | Mass Dots: Nanoparticle Isotope Tags |
| CN105527333A (en) * | 2016-01-25 | 2016-04-27 | 广西壮族自治区环境监测中心站 | Method for determining heavy metal content of sugarcane with electric heating board digestion/ICP-MS (inductively coupled plasma mass spectrometry) methods |
Non-Patent Citations (7)
| Title |
|---|
| 中国食品药品检定研究院: "《中国食品药品检验检测技术系列丛书 中国药品检验标准操作规范 2019版》", 31 August 2019, pages: 256 - 258 * |
| 甘周阳 等: "ICP-MS法测定多西他赛原料药中的10种金属元素杂质", 《广东化工》 * |
| 甘周阳 等: "ICP-MS法测定多西他赛原料药中的10种金属元素杂质", 《广东化工》, vol. 45, no. 6, 31 December 2018 (2018-12-31), pages 205 - 209 * |
| 许雯雯 等: "ICP-MS 法测定盐酸安舒法辛缓释片中7个元素杂质含量", 《药物分析杂志》 * |
| 许雯雯 等: "ICP-MS 法测定盐酸安舒法辛缓释片中7个元素杂质含量", 《药物分析杂志》, vol. 39, no. 2, 28 February 2019 (2019-02-28), pages 319 - 327 * |
| 陈阳 等: "化学原料药中19种金属杂质的检测研究", 《药物分析杂志》 * |
| 陈阳 等: "化学原料药中19种金属杂质的检测研究", 《药物分析杂志》, vol. 32, no. 4, 30 April 2012 (2012-04-30), pages 631 - 635 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111678972A (en) * | 2020-06-19 | 2020-09-18 | 广州汇标检测技术中心 | Method for detecting impurity elements in bulk drugs |
| CN112326765A (en) * | 2020-10-30 | 2021-02-05 | 淄博高新技术产业开发区生物医药研究院 | Detection method for analyzing content of 24 element impurities in insulin at one time |
| CN114152661A (en) * | 2021-12-02 | 2022-03-08 | 南通联亚药业有限公司 | ICP-MS detection method for element impurities in conjugated estrogen bulk drug containing high-salt matrix |
| CN114152661B (en) * | 2021-12-02 | 2024-03-19 | 南通联亚药业股份有限公司 | ICP-MS detection method for elemental impurities in conjugated estrogens bulk drug containing high-salt matrix |
| CN114487079A (en) * | 2021-12-31 | 2022-05-13 | 乳源东阳光药业有限公司 | Analysis method for measuring elemental impurity silver in rosuvastatin calcium by ICP-MS |
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