CN113189189A - Medicine detection method and quality control method of compound calcium gluconate oral solution - Google Patents
Medicine detection method and quality control method of compound calcium gluconate oral solution Download PDFInfo
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 42
- 229940042228 calcium gluconate oral solution Drugs 0.000 title claims abstract description 41
- 238000001514 detection method Methods 0.000 title claims abstract description 26
- 239000003814 drug Substances 0.000 title claims abstract description 25
- 238000003908 quality control method Methods 0.000 title claims abstract description 22
- 229940079593 drug Drugs 0.000 title claims description 16
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims abstract description 81
- 229910052782 aluminium Inorganic materials 0.000 claims abstract description 30
- 238000002360 preparation method Methods 0.000 claims abstract description 18
- 239000012086 standard solution Substances 0.000 claims description 56
- 239000011550 stock solution Substances 0.000 claims description 48
- 239000000243 solution Substances 0.000 claims description 46
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 33
- 229910017604 nitric acid Inorganic materials 0.000 claims description 33
- 239000012488 sample solution Substances 0.000 claims description 30
- 238000007865 diluting Methods 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 19
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical group [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 17
- 229960005069 calcium Drugs 0.000 claims description 11
- 229910052791 calcium Inorganic materials 0.000 claims description 11
- 239000011575 calcium Substances 0.000 claims description 11
- 239000000523 sample Substances 0.000 claims description 11
- 239000012085 test solution Substances 0.000 claims description 10
- 239000012490 blank solution Substances 0.000 claims description 9
- 238000001095 inductively coupled plasma mass spectrometry Methods 0.000 claims description 8
- 229910052706 scandium Inorganic materials 0.000 claims description 6
- SIXSYDAISGFNSX-UHFFFAOYSA-N scandium atom Chemical compound [Sc] SIXSYDAISGFNSX-UHFFFAOYSA-N 0.000 claims description 6
- 238000002372 labelling Methods 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 238000007689 inspection Methods 0.000 abstract description 16
- 230000000694 effects Effects 0.000 abstract description 4
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- 239000000047 product Substances 0.000 description 29
- 239000012535 impurity Substances 0.000 description 5
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000011574 phosphorus Substances 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 229960004494 calcium gluconate Drugs 0.000 description 2
- 239000004227 calcium gluconate Substances 0.000 description 2
- 235000013927 calcium gluconate Nutrition 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 206010003694 Atrophy Diseases 0.000 description 1
- 206010006956 Calcium deficiency Diseases 0.000 description 1
- 235000005976 Citrus sinensis Nutrition 0.000 description 1
- 240000002319 Citrus sinensis Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 208000003217 Tetany Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
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- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 1
- 239000001527 calcium lactate Substances 0.000 description 1
- 229960002401 calcium lactate Drugs 0.000 description 1
- 235000011086 calcium lactate Nutrition 0.000 description 1
- 230000003913 calcium metabolism Effects 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 229940069978 calcium supplement Drugs 0.000 description 1
- NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- -1 compound calcium gluconate Chemical class 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
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- 235000013305 food Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000000777 hematopoietic system Anatomy 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 238000009616 inductively coupled plasma Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
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- 210000001672 ovary Anatomy 0.000 description 1
- 231100000719 pollutant Toxicity 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 208000007442 rickets Diseases 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 229910052712 strontium Inorganic materials 0.000 description 1
- CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
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Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/62—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosols; by investigating electric discharges, e.g. emission of cathode
-
- 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
Abstract
The invention discloses a medicine detection method and a quality control method of compound calcium gluconate oral solution, which comprises the inspection of aluminum element. Aiming at the defect that the quality control standard of a medicament, in particular a compound calcium gluconate oral solution is not perfect, the quality control method of the preparation is researched, the aluminum inspection is added on the basis of the original quality control standard, and the quality control standard is improved, so that the quality of the product and the clinical curative effect of the preparation are ensured.
Description
Technical Field
The invention relates to a medicine quality detection method, in particular to a medicine detection method and a quality control method of compound calcium gluconate oral solution.
Background
At present, the existing quality standards of most medicines comprise detection of items such as characters, identification, inspection, content and the like, but the inspection items do not have aluminum element impurity control items, and the quality standards cannot perfect and effectively control the product quality; aluminum element is not needed by human bodies and has terrible harm to human bodies, the world health organization formally determines aluminum as a food pollutant in 1989, when the content of the aluminum element in the human bodies is too high, the absorption of phosphorus, strontium, iron, calcium and other elements by intestinal tracts can be influenced, insoluble aluminum phosphate is formed in the intestinal tracts and is discharged out of the bodies along with excrement, phosphorus deficiency influences the absorption of calcium (enough calcium phosphate is not generated), osteoporosis and fracture can be easily caused, and most of the aluminum in the bodies has adverse effects on the central nervous system, the digestive system, the brain, the liver, the bone, the kidney, cells, the hematopoietic system, the immune function and the like; meanwhile, the compound preparation can interfere acid-base balance in the body of a pregnant woman, cause ovary atrophy, influence fetal growth, influence phosphorus and calcium metabolism of an organism and the like, aluminum is deposited in the brain and the skin, the whole aging process of the human body can be accelerated, and particularly, the elasticity of the skin is obviously reduced and wrinkles are increased.
The compound calcium gluconate oral solution is composed of calcium gluconate, calcium lactate, sucrose, oral glucose, lactic acid, sweet orange essence, purified water and the like, can be used for the prevention and adjuvant treatment of calcium deficiency, such as osteoporosis, tetany, rickets, calcium supplement for children, pregnant and lactating women, menopausal women, and the elderly, and compound calcium gluconate oral liquid has properties, identification, examination, content detection, no aluminum impurity control item, the quality standard can not perfect and effectively control the product quality, because element impurities can not provide any treatment effect for patients, and the excessive aluminum element can cause side effects such as renal function injury and the like, the quality of the compound calcium gluconate oral solution can be controlled according to the existing quality standard, but the limit of aluminum element in the compound calcium gluconate oral solution cannot be controlled.
Disclosure of Invention
The invention aims to solve the technical problems that part of the existing quality standards of medicines have detection of items such as characters, identification, inspection, content and the like, but the inspection items do not have aluminum element impurity control items, and the quality standards cannot perfect and effectively control the product quality, and aims to provide a medicine detection method and a quality control method of compound calcium gluconate oral solution to solve the problems.
The invention is realized by the following technical scheme:
the drug detection method comprises the determination of aluminum element.
The invention adds the detection item of the aluminum element in the drug detection method, the existing drug detection indexes do not refer to the determination of the aluminum element, and the aluminum element in the drug cannot be monitored.
The drug detection method comprises the following steps of:
a. preparing a standard solution;
b. preparing a blank solution;
c. preparing an internal standard solution;
d. preparing a test solution;
e. preparing a labeling sample solution;
f. and (3) determination: the selected isotope is27Al、45Sc，27Al and45taking Sc as an internal standard, introducing an internal standard solution into an internal standard tube of the instrument on line, sequentially inserting the sample tube of the instrument into standard solution with each concentration for determination, sequentially increasing the concentration of the standard solution with each concentration, drawing a standard curve by taking the measured value as a vertical coordinate and the concentration as a horizontal coordinate, inserting the sample tube of the instrument into a sample solution for determination, taking the average value of 3 readings, calculating the measured concentration of aluminum element from the standard curve, and calculating the amount of the aluminum element according to the measured concentration ng/ml of the aluminum element as 100 ml/1000.
The method determines the amount of the aluminum element in the medicament by referring to the existing inductively coupled plasma mass spectrometry, and the determination result is accurate.
The quality control method of the compound calcium gluconate oral solution comprises the determination of aluminum element.
The quality control method of the compound calcium gluconate oral solution determines the amount of aluminum element in the compound calcium gluconate oral solution according to an inductively coupled plasma mass spectrometry method, and comprises the following specific steps:
A. preparing a standard solution by the following steps:
standard stock solution: precisely measuring 1ml of aluminum single element standard solution, placing the aluminum single element standard solution in a 100ml measuring flask, adding 5% nitric acid solution to dilute the solution to a scale, and shaking up to obtain standard product stock solution containing 10 microgram of aluminum per 1 ml;
standard solutions of series concentrations: precisely measuring standard product stock solutions 0.1 ml, 0.25 ml, 0.5ml, 1.0ml, 1.5ml and 2.0ml, putting the standard product stock solutions into a 50ml measuring flask, adding 5.5ml of a calcium unit element standard solution, diluting the standard product stock solutions to a scale by using a 5% nitric acid solution, shaking up to obtain standard product stock solutions with aluminum content of 20ng, 50 ng, 100ng, 200 ng, 300 ng and 400ng in each 1ml, precisely measuring 2.5ml of the standard product stock solutions with aluminum content of 100ng in each 1ml, putting the standard product stock solutions into the 50ml measuring flask, adding 5.5ml of the calcium unit element standard solution, diluting the standard product stock solutions to the scale by using the 5% nitric acid solution, and shaking up to obtain the standard product stock solutions with aluminum content of 5ng in each 1 ml;
B. the preparation method of the blank solution comprises the following steps: taking 5.5ml of calcium single element standard solution, placing the calcium single element standard solution in a 50ml measuring flask, diluting the calcium single element standard solution to a scale with 5% nitric acid solution, and shaking up;
C. preparing an internal standard solution by the following steps: accurately measuring a proper amount of scandium single element standard solution, and diluting with water to prepare a solution containing 20ng of scandium per 1 ml;
D. the preparation method of the test solution comprises the following steps: taking 10 contents of the product, mixing uniformly, precisely measuring 1ml of the contents, placing the contents in a 100ml measuring flask, diluting the contents to a scale with 5% nitric acid solution, and shaking uniformly;
E. preparing a standard sample solution, wherein the preparation method comprises the following steps:
spiked sample solutions at 20ppb level: precisely measuring 1ml of content, placing in a 100ml measuring flask, precisely adding 0.2ml of standard stock solution, diluting with 5% nitric acid solution to scale, and shaking;
spiked sample solutions at 50ppb level: precisely measuring 1ml of content, placing in a 100ml measuring flask, precisely adding 0.5ml of standard stock solution, diluting with 5% nitric acid solution to scale, and shaking;
100ppb level of spiked sample solution: precisely measuring 1ml of content, placing the content in a 100ml measuring flask, precisely adding 1.0ml of standard stock solution, diluting with 5% nitric acid solution to scale, and shaking up;
spiked sample solutions at 150ppb level: precisely measuring 1ml of content, placing the content in a 100ml measuring flask, precisely adding 1.5ml of standard stock solution, diluting with 5% nitric acid solution to scale, and shaking up;
200ppb level of spiked sample solution: precisely measuring 1ml of content, placing the content in a 100ml measuring flask, precisely adding 2.0ml of standard stock solution, diluting with 5% nitric acid solution to scale, and shaking up;
300ppb level of spiked sample solution: precisely measuring 1ml of content, placing in a 100ml measuring flask, precisely adding 3.0ml of standard stock solution, diluting with 5% nitric acid solution to scale, and shaking;
F. and (3) determination: the selected isotope is27Al、45Sc，27Al and45taking Sc as an internal standard, introducing an internal standard solution into an internal standard tube of the instrument on line, sequentially inserting the sample tube of the instrument into standard solution with each concentration for determination, sequentially increasing the concentration of the standard solution with each concentration, drawing a standard curve by taking a measured value (the average value of 3 readings) as a vertical coordinate and the concentration as a horizontal coordinate, inserting the sample tube of the instrument into a sample solution for determination, taking the average value of the 3 readings, calculating the measured concentration of aluminum element from the standard curve, and calculating the amount of the aluminum element according to the measured concentration ng/ml of the aluminum element as 100 ml/1000.
The invention applies aluminum element detection to the compound calcium gluconate oral solution, and in order to ensure that the product quality is effectively controlled, the invention researches the quality standard of the compound calcium gluconate oral solution, determines the inspection of the added aluminum in the quality standard of the compound calcium gluconate oral solution, more scientifically and effectively controls the product quality by inspecting the aluminum in the compound calcium gluconate oral solution, and solves the problem that the quality standard can not perfectly and effectively control the product quality because an inspection item in the existing compound calcium gluconate oral solution quality standard has no element impurity control item.
The aluminum content of each 1ml of the compound calcium gluconate oral solution is not more than 20 mug.
Compared with the prior art, the invention has the following advantages and beneficial effects:
1. the medicine detection method of the invention adds an aluminum element check item;
2. the quality control method of the compound calcium gluconate oral solution provided by the invention researches the quality standard of the compound calcium gluconate oral solution, and determines the inspection of the added aluminum in the quality standard of the compound calcium gluconate oral solution;
3. the quality control method of the compound calcium gluconate oral solution has good feasibility and can achieve the aim of effectively controlling the product quality.
Drawings
The accompanying drawings, which are included to provide a further understanding of the embodiments of the invention and are incorporated in and constitute a part of this application, illustrate embodiment(s) of the invention and together with the description serve to explain the principles of the invention. In the drawings:
fig. 1 is a standard curve chart of the examination of aluminum element in the compound calcium gluconate oral solution of the invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail below with reference to examples and accompanying drawings, and the exemplary embodiments and descriptions thereof are only used for explaining the present invention and are not meant to limit the present invention.
Example 1
The drug detection method comprises the inspection of aluminum element. According to the invention, the inspection item of the aluminum element is added in the drug detection method, the existing drug detection indexes do not refer to the aluminum element inspection, and the aluminum element in the drug cannot be monitored; a plurality of methods for measuring the aluminum element appear at present, mainly comprising a spectrophotometry method, an atomic absorption method, an inductively coupled plasma method and the like, and the method preferably selects the inductively coupled plasma mass spectrometry to detect the aluminum element in the medicament.
Example 2
The quality control method of the compound calcium gluconate oral solution comprises the steps of checking aluminum element; the invention uses the aluminum element inspection into the specific medicine, and pertinently enhances the quality monitoring strength of the compound calcium gluconate oral solution.
In order to ensure that the product quality is effectively controlled, the quality standard of the compound calcium gluconate oral solution is researched, and the inspection of the added aluminum element in the quality standard of the compound calcium gluconate oral solution is determined.
The quality control method of the compound calcium gluconate oral solution comprises the steps of detecting the content of aluminum element by an inductively coupled plasma mass spectrometry; the specific steps of the inductively coupled plasma mass spectrometry for detecting the aluminum element are as follows:
A. preparation of standard solution:
standard stock solution: precisely measuring 1ml of aluminum single element standard solution, placing the aluminum single element standard solution in a 100ml measuring flask, adding 5% nitric acid solution to dilute the solution to a scale, and shaking up to obtain standard product stock solution containing 10 microgram of aluminum per 1 ml.
Standard solutions of series concentrations: precisely measuring standard product stock solutions of 0.1 ml, 0.25 ml, 0.5ml, 1.0ml, 1.5ml and 2.0ml, putting the standard product stock solutions into a 50ml measuring flask, adding 5.5ml of a calcium unit element standard solution, diluting the standard product stock solutions to a scale by using a 5% nitric acid solution, shaking up to obtain standard product stock solutions with aluminum content of 20ng, 50 ng, 100ng, 200 ng, 300 ng and 400ng in each 1ml, precisely measuring 2.5ml of the standard product stock solutions with aluminum content of 100ng in each 1ml, putting the standard product stock solutions into the 50ml measuring flask, adding 5.5ml of the calcium unit element standard solution, diluting the standard product stock solutions to the scale by using the 5% nitric acid solution, and shaking up to obtain the standard product stock solutions with aluminum content of 5ng in each 1 ml.
B. Preparation of a blank solution: taking 5.5ml of calcium single element standard solution, putting the calcium single element standard solution into a 50ml measuring flask, diluting the calcium single element standard solution to a scale with 5% nitric acid solution, and shaking up.
C. Preparation of internal standard solution: an appropriate amount of scandium single element standard solution is precisely measured and diluted by water to prepare a solution containing 20ng of scandium per 1 ml.
D. Preparation of a test solution: the 10 contents of the product are uniformly mixed, 1ml of the contents are precisely measured and placed in a 100ml measuring flask, diluted to the scale with 5% nitric acid solution and shaken up.
E. Preparation of a labeling sample solution:
spiked sample solutions at 20ppb level: precisely measuring 1ml of the content, placing the content in a 100ml measuring flask, precisely adding 0.2ml of standard stock solution, diluting to scale with 5% nitric acid solution, and shaking up.
Spiked sample solutions at 50ppb level: precisely measuring 1ml of the content, placing the content in a 100ml measuring flask, precisely adding 0.5ml of standard stock solution, diluting to scale with 5% nitric acid solution, and shaking up.
100ppb level of spiked sample solution: precisely measuring 1ml of the content, placing the content in a 100ml measuring flask, precisely adding 1.0ml of standard stock solution, diluting to scale with 5% nitric acid solution, and shaking up.
Spiked sample solutions at 150ppb level: precisely measuring 1ml of the content, placing the content in a 100ml measuring flask, precisely adding 1.5ml of standard stock solution, diluting to scale with 5% nitric acid solution, and shaking up.
200ppb level of spiked sample solution: precisely measuring 1ml of the content, placing the content in a 100ml measuring flask, precisely adding 2.0ml of standard stock solution, diluting to scale with 5% nitric acid solution, and shaking up.
300ppb level of spiked sample solution: precisely measuring 1ml of the content, placing the content in a 100ml measuring flask, precisely adding 3.0ml of standard stock solution, diluting to scale with 5% nitric acid solution, and shaking up.
F. And (3) determination: the selected isotope is27Al、45Sc，27Al and45taking Sc as an internal standard, and introducing an internal standard tube of the instrument into an internal standard solution on line. The sample tube of the instrument is inserted into the standard solution of each concentration in turn for measurement (the concentration is increased in turn), a standard curve is drawn with the measured value (the average value of 3 readings) as the ordinate and the concentration as the abscissa, the sample tube of the instrument is inserted into the sample solution for measurement, the average value of 3 readings is taken, the measured concentration of the aluminum element is calculated from the standard curve, and the amount of the aluminum element is calculated according to the measured concentration (ng/ml) × 100 (ml)/1000.
The aluminum content of each 1ml of the compound calcium gluconate oral solution is not more than 20 mug.
Test example 1
In order to verify the feasibility of the aluminum element inspection method in the compound calcium gluconate oral solution in embodiment 2 of the present invention, the following experimental studies were performed in this experimental example:
(1) linearity and range
A series of concentration standard solutions were prepared according to the standard solution preparation method of example 2, and a curve of concentration and response of aluminum element was plotted by sampling the series of concentration standard solutions, wherein f (x) is 730.2627 x +1355.2310, and r is 1.0000.
And (4) conclusion: the linear relation of the aluminum element in the concentration range of 5-400 ng/ml is good, and is shown in figure 1.
(2) Detection limit and quantification limit
Blank solutions were prepared according to the method of preparing blank solutions of example 2, and the blank solutions were measured 11 times in succession, and the standard deviation SD of the 11 blank values was calculated, the instrumental detection limit was calculated according to 3.3 SD/k (k is the slope of the standard curve), and the instrumental quantitation limit was calculated according to 10 SD/k (k is the slope of the standard curve).
And (4) conclusion: the detection limit of the instrument is 0.26ng/ml, and the quantification limit of the instrument is 0.79ng/ml, which is shown in Table 1.
TABLE 1 examination of detection and quantitation limits
The concentration of the solution at the lowest point of linearity was taken as the limit of quantitation of the method, the limit of quantitation of the method was 5ng/ml, the report limit was 0.5. mu.g/ml (i.e., limit of quantitation of the method 5 (ng/ml). times dilution 100(ml)), corresponding to 2.5% of the limit (20. mu.g/ml), the lowest concentration point of the standard curve was sampled 6 times in duplicate, and the relative standard deviation of the response values was 2.4% for 6 determinations.
(3) Accuracy of
The method of preparing the spiked solutions in example 2 was followed to prepare spiked solutions, and the accuracy of the method was examined at six spiked concentration levels of 20ppb, 50ppb, 100ppb, 150ppb, 200ppb, and 300ppb, respectively, 3 parts of the solutions were prepared in parallel for each concentration level according to the method of preparing the spiked sample solutions at each level in the preparation of the solutions, and the average recovery rate at each concentration level was measured.
And (4) conclusion: the recovery rate of each concentration level meets the requirements of the verification guiding principle of the analysis method of Chinese pharmacopoeia 9101 on the content of the component to be determined and the limit of the recovery rate in a sample shown in a table 2. The results are shown in Table 2.
TABLE 2 accuracy investigation results
(4) Repeatability of
6 test solutions were prepared in parallel, and the relative standard deviation of the 6 test solutions was measured to find that the RSD was 1.60%, and the results are shown in Table 3.
(5) Intermediate precision
6 test solutions were prepared in parallel by different persons at different times, and the relative standard deviation of 12 test solutions was measured, and the RSD was 1.87%, and the results are shown in Table 3.
TABLE 3 results of precision investigation
Through a series of tests of linearity and range, detection limit and quantification limit, accuracy, repeatability, intermediate precision and the like, the method selects the inductively coupled plasma mass spectrometry to detect the aluminum element. The result shows that the aluminum element inspection method is feasible and can achieve the aim of effectively controlling the product quality of the compound calcium gluconate oral solution.
The above-mentioned embodiments are intended to illustrate the objects, technical solutions and advantages of the present invention in further detail, and it should be understood that the above-mentioned embodiments are merely exemplary embodiments of the present invention, and are not intended to limit the scope of the present invention, and any modifications, equivalent substitutions, improvements and the like made within the spirit and principle of the present invention should be included in the scope of the present invention.
Claims (10)
1. The drug detection method is characterized by comprising the determination of aluminum element.
2. The drug detection method according to claim 1, wherein the method for measuring the aluminum element measures the amount of the aluminum element in the drug by inductively coupled plasma mass spectrometry, and comprises the following steps:
a. preparing a standard solution;
b. preparing a blank solution;
c. preparing an internal standard solution;
d. preparing a test solution;
e. preparing a labeling sample solution;
f. and (3) determination: the selected isotope is27Al、45Sc，27Al and45taking Sc as an internal standard, introducing an internal standard solution into an internal standard tube of the instrument on line, sequentially inserting the sample tube of the instrument into standard solution with each concentration for determination, sequentially increasing the concentration of the standard solution with each concentration, drawing a standard curve by taking the measured value as a vertical coordinate and the concentration as a horizontal coordinate, inserting the sample tube of the instrument into a sample solution for determination, taking the average value of 3 readings, calculating the measured concentration of aluminum element from the standard curve, and calculating the amount of the aluminum element according to the measured concentration ng/ml of the aluminum element as 100 ml/1000.
3. The quality control method of the compound calcium gluconate oral solution is characterized by comprising the determination of aluminum element.
4. The method for controlling the quality of the compound calcium gluconate oral solution according to claim 3, wherein the method for determining the amount of aluminum in the compound calcium gluconate oral solution by inductively coupled plasma mass spectrometry comprises the following steps:
A. preparing a standard solution;
B. preparing a blank solution;
C. preparing an internal standard solution;
D. preparing a test solution;
E. preparing a labeling sample solution;
F. and (3) determination: the selected isotope is27Al、45Sc，27Al and45taking Sc as an internal standard, introducing an internal standard solution into an internal standard tube of the instrument on line, sequentially inserting the sample tube of the instrument into standard solution with each concentration for determination, sequentially increasing the concentration of the standard solution with each concentration, drawing a standard curve by taking the measured value as a vertical coordinate and the concentration as a horizontal coordinate, inserting the sample tube of the instrument into a sample solution for determination, taking the average value of 3 readings, calculating the measured concentration of aluminum element from the standard curve, and calculating the amount of the aluminum element according to the measured concentration ng/ml of the aluminum element as 100 ml/1000.
5. The quality control method of the compound calcium gluconate oral solution according to claim 3, wherein the aluminum content in each 1ml of the compound calcium gluconate oral solution is not more than 20 μ g.
6. The quality control method of the compound calcium gluconate oral solution according to claim 4, wherein the preparation method of the standard solution in the step A comprises the following steps:
standard stock solution: precisely measuring 1ml of aluminum single element standard solution, placing the aluminum single element standard solution in a 100ml measuring flask, adding 5% nitric acid solution to dilute the solution to a scale, and shaking up to obtain standard product stock solution containing 10 microgram of aluminum per 1 ml;
standard solutions of series concentrations: precisely measuring standard product stock solutions of 0.1 ml, 0.25 ml, 0.5ml, 1.0ml, 1.5ml and 2.0ml, putting the standard product stock solutions into a 50ml measuring flask, adding 5.5ml of a calcium unit element standard solution, diluting the standard product stock solutions to a scale by using a 5% nitric acid solution, shaking up to obtain standard product stock solutions with aluminum content of 20ng, 50 ng, 100ng, 200 ng, 300 ng and 400ng in each 1ml, precisely measuring 2.5ml of the standard product stock solutions with aluminum content of 100ng in each 1ml, putting the standard product stock solutions into the 50ml measuring flask, adding 5.5ml of the calcium unit element standard solution, diluting the standard product stock solutions to the scale by using the 5% nitric acid solution, and shaking up to obtain the standard product stock solutions with aluminum content of 5ng in each 1 ml.
7. The quality control method of the compound calcium gluconate oral solution according to claim 4, wherein the preparation method of the blank solution in the step B comprises the following steps: taking 5.5ml of calcium single element standard solution, putting the calcium single element standard solution into a 50ml measuring flask, diluting the calcium single element standard solution to a scale with 5% nitric acid solution, and shaking up.
8. The quality control method of the compound calcium gluconate oral solution according to claim 4, wherein the preparation method of the internal standard solution in the step C comprises the following steps: an appropriate amount of scandium single element standard solution is precisely measured and diluted by water to prepare a solution containing 20ng of scandium per 1 ml.
9. The quality control method of the compound calcium gluconate oral solution according to claim 4, wherein the preparation method of the test solution in the step D is as follows: the 10 contents of the product are uniformly mixed, 1ml of the contents are precisely measured and placed in a 100ml measuring flask, diluted to the scale with 5% nitric acid solution and shaken up.
10. The quality control method of the compound calcium gluconate oral solution according to claim 4, wherein the preparation method of the standard sample solution added in the step E comprises the following steps:
spiked sample solutions at 20ppb level: precisely measuring 1ml of content, placing in a 100ml measuring flask, precisely adding 0.2ml of standard stock solution, diluting with 5% nitric acid solution to scale, and shaking;
spiked sample solutions at 50ppb level: precisely measuring 1ml of content, placing in a 100ml measuring flask, precisely adding 0.5ml of standard stock solution, diluting with 5% nitric acid solution to scale, and shaking;
100ppb level of spiked sample solution: precisely measuring 1ml of content, placing the content in a 100ml measuring flask, precisely adding 1.0ml of standard stock solution, diluting with 5% nitric acid solution to scale, and shaking up;
spiked sample solutions at 150ppb level: precisely measuring 1ml of content, placing the content in a 100ml measuring flask, precisely adding 1.5ml of standard stock solution, diluting with 5% nitric acid solution to scale, and shaking up;
200ppb level of spiked sample solution: precisely measuring 1ml of content, placing the content in a 100ml measuring flask, precisely adding 2.0ml of standard stock solution, diluting with 5% nitric acid solution to scale, and shaking up;
300ppb level of spiked sample solution: precisely measuring 1ml of the content, placing the content in a 100ml measuring flask, precisely adding 3.0ml of standard stock solution, diluting to scale with 5% nitric acid solution, and shaking up.
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