CN109709237A - A kind of calcium carbonate D3The related substance detecting method of chewable tablets - Google Patents
A kind of calcium carbonate D3The related substance detecting method of chewable tablets Download PDFInfo
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- CN109709237A CN109709237A CN201811491825.2A CN201811491825A CN109709237A CN 109709237 A CN109709237 A CN 109709237A CN 201811491825 A CN201811491825 A CN 201811491825A CN 109709237 A CN109709237 A CN 109709237A
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Abstract
The invention discloses a kind of calcium carbonate D3The related substance detecting method of chewable tablets, the calcium carbonate D provided3Vitamin D in chewable tablets3Related substance HPLC measuring method stability and it is reproducible, separating degree is good, can accurate qualitative and quantitative analysis calcium carbonate D3Vitamin D in chewable tablets3Main related substance, thus it is objective, comprehensively and accurately evaluate calcium carbonate D3The quality of chewable tablets, control to product quality and guarantees that clinical efficacy has important practical significance.
Description
[technical field]
The present invention relates to the technical field of Pharmaceutical Analysis technology, especially a kind of calcium carbonate D3The related substance of chewable tablets is examined
The technical field of survey method.
Calcium carbonate D described in full text3Chewable tablets, the entitled calcium carbonate D of national standard3Chewable tablets (II).
[background technique]
Calcium carbonate D3Chewable tablets is a kind of compound preparation, and this product contains vitamin D3(C27H44O it) should be the 90.0% of labelled amount
~120.0%；Calcium carbonate (CaCO3) it should be the 95.0%~105.0% of labelled amount.Calcium is to maintain human nerve, muscle, bone
Substance necessary to bone system, cell membrane and capillary permeability normal function.Vitamin D can participate in the metabolism of calcium and phosphorus,
Promote it to absorb and plays an important role to New bone formation, calcium carbonate D3Chewable tablets is the compound preparation of a kind of calcic and vitamin D,
For the calcium complement agent of gestation and breast feeding women, climacteric women, the elderly and children etc., and help to prevent and treat osteoporosis
Disease.Under the conditions of the diet of current China resident, depends merely on food and be often difficult to meet human body to the needs of calcium and vitamin D.With
People replenish the calcium the raising of consciousness, the country is in great demand to calcium supplementing product.
Vitamin D3It is unstable, vitamin D is provided in Chinese Pharmacopoeia standard3Bulk pharmaceutical chemicals need shading, nitrogen charging, sealing, Yu Leng
Place saves.Vitamin D3The related substance of the perishable generation of light or air, the mainly isomers of its photothermal conversion are met, including preceding
Vitamin D3, trans-vitamin D3With tachysterol D3, their path for transformation is as shown in figure 4, i.e. vitamin D3It is heated to generate preceding dimension
Raw element D3, light-exposed generation trans-vitamin D3, provitamin D3Light generates tachysterol D3, due to provitamin D3Belong to effectively at
Point, therefore main related substance is trans-vitamin D3With tachysterol D3。
However the calcium carbonate and vitamin D sold in worldwide at present3Calcium-supplementing preparation, shortcoming to vitamin
Related substance control.Currently, not yet retrieving " calcium carbonate and vitamin D3Calcium-supplementing preparation " in vitamin D3Related substance
Measuring method.Both at home and abroad temporarily not to " calcium carbonate and vitamin D3Calcium-supplementing preparation " in vitamin D3Related substance carry out
Control.
It is closed to hold drug quality, guarantees product quality, guarantee people's drug safety.It needs to calcium carbonate D3Nozzle
Chew vitamin D in piece3Related substance effectively controlled.Therefore, a kind of calcium carbonate D is studied3Vitamin D in chewable tablets3's
Related substance HPLC measuring method, this seems especially urgent for medicine manufacture.
[summary of the invention]
The object of the invention is to solve the problems of the prior art, a kind of calcium carbonate D is proposed3The related substance of chewable tablets
Detection method, strong operability, accuracy are high, can control denier vitamin D3The related substance of the key of preparation.
To achieve the above object, the present invention is achieved through the following technical solutions:
A kind of calcium carbonate D3The related substance detecting method of chewable tablets, includes the following steps:
A) it prepares test solution: being protected from light operation, take and be equivalent to containing vitamin D3The calcium carbonate D of 30 μ g3Chewable tablets is ground
Thin particle, sets in brown measuring bottle, the diformazan for the 2,6-di-tert-butyl p-cresol that the concentration that 20~100ml is added is 0.2mg/ml
Dimethyl sulfoxide in the mixed solution of the mixed solution of base sulfoxide and water, the dimethyl sulfoxide and water: the volume ratio of water is 10:
2, then, sonic oscillation, and constantly shake, precision adds mass fraction to be the n-hexane of 0.02% 2,6-di-tert-butyl p-cresol
5~25ml of solution after shaking, is centrifuged, and precision measures 0.5~10ml of supernatant liquor, and with being dried with nitrogen, residue adds quality point
Number makes to dissolve for 0.5~2ml of hexane solution of 0.02% 2,6-di-tert-butyl p-cresol, as test solution；
B) prepare contrast solution: precision measures 100 μ l of test solution, sets in 10ml measuring bottle, adds the mass fraction to be
The hexane solution of 0.02% 2,6-di-tert-butyl p-cresol is diluted to scale, shakes up, as contrast solution；
C) prepare reference substance solution: another precision weighs trans-vitamin D3Reference substance with n-hexane dissolution and quantifies dilution
It is made containing about the solution of 0.1 μ g in every 1ml, as reference substance solution；
D) liquid chromatographic detection: precision measures test solution, contrast solution and each 200 μ l of reference substance solution, infuses respectively
Enter liquid chromatograph, record to 1.5 times of principal component peak retention time, in test solution chromatogram, if any with the life of trans- dimension
Plain D3Retention time consistent chromatographic peak in peak must not cross 1.0% by external standard method with calculated by peak area, if any with tachysterol D3Peak is protected
The chromatographic peak of time consistency is stayed, peak area is not greater than the 1.0% of contrast solution main peak area, the tachysterol D3Peak and dimension
Raw element D3Relative retention time is about 1.1.
Preferably, the time of sonic oscillation described in step a) is 5~30min, and ultrasonic water bath temperature is kept not surpass
Crossing 30 DEG C, the shaking time is 5~30min, and the centrifugation time is 10~30min, the revolving speed of centrifugation is 4000~
12000rpm。
Preferably, testing conditions include the following:
1. the stationary phase of chromatographic column is silica gel, the partial size of silicagel column is 5 μm, and column length is 150~250mm, and internal diameter is
4.6mm；
2. the mixed liquor that mobile phase is made of the n-amyl alcohol that volume ratio is 2.5~3.5:996.5~997.5 and n-hexane；
3. flow velocity is 1.0~2.5ml/min；
4. Detection wavelength is 254nm；
5. sampling volume is 50~250 μ l.
The calcium carbonate D among the above3Chewable tablets, the entitled calcium carbonate D of national standard3Chewable tablets (II).
Beneficial effects of the present invention: the present invention preferably goes out optimal analysis condition and test solution after passing through many experiments
Preparation method.Show calcium carbonate D provided by the invention through many experiments verifying3Vitamin D in chewable tablets3Related substance HPLC
Measuring method stability and it is reproducible, separating degree is good, can accurate qualitative and quantitative analysis calcium carbonate D3Life is tieed up in chewable tablets
Plain D3Main related substance, thus it is objective, comprehensively and accurately evaluate calcium carbonate D3The quality of chewable tablets, the control to product quality
It makes and guarantees that clinical efficacy has important practical significance.
Feature and advantage of the invention will be described in detail by embodiment combination attached drawing.
[Detailed description of the invention]
Fig. 1 is impurity reference substance mixed solution HPLC figure；
Fig. 2 is to lack vitamin D3Negative blank solution HPLC figure；
Fig. 3 is calcium carbonate D3Chewable tablets test solution HPLC figure；
Fig. 4 is vitamin D3With the path for transformation figure of its isomers；
Fig. 5 is vitamin D3Linear graph；
Fig. 6 is tachysterol D3Linear graph.
In Fig. 1,1- provitamin D3；2- trans-vitamin D3；3- friction speed sterol D3；4- vitamin D3；5- tachysterol D3With
6- vitamin D3It is former.
[specific embodiment]
In order to make those skilled in the art more fully understand technical solution of the present invention, disclose further below some non-
Limiting embodiment, the present invention is described in further detail.The method is conventional method unless otherwise instructed.The original
Material can obtain unless otherwise specified from public commercial source.
One, specific embodiment:
Instrument is using Japanese Shimadzu LC-10MAvp high performance liquid chromatograph；Japanese Shimadzu AUW220D electronic analytical balance.
Material is the calcium carbonate D of our company's solid Workshop Production3Chewable tablets.
Vitamin D3Reference substance is purchased from National Institute for Food and Drugs Control, lot number 100061-201208.
N-hexane is chromatographically pure.
Other reagents are that analysis is pure.
1, impurity reference substance mixed solution is prepared:
Vitamin D is taken respectively3, provitamin D3, trans-vitamin D3, tachysterol D3, friction speed sterol D3And vitamin D3It is former
Impurity reference substance mixed solution is made with n-hexane in reference substance.
2, prepared by test solution:
It is protected from light operation, takes and is equivalent to containing vitamin D3The calcium carbonate D of 30 μ g3The finely ground particle of chewable tablets sets 200ml palm fibre
In colo(u)r specification bottle, the mixing of the dimethyl sulfoxide and water of the 2,6-di-tert-butyl p-cresol that the concentration that 50ml is added is 0.2mg/ml is molten
Dimethyl sulfoxide in the mixed solution of liquid, the dimethyl sulfoxide and water: the volume ratio of water is 10:2, then, sonic oscillation
15min, and constantly shake, keep ultrasonic water bath temperature to be no more than 30 DEG C, precision adds mass fraction to be 0.02% 2,6-, bis- uncle
The hexane solution 10ml of butyl paracresol after shaking 15min, is centrifuged 15min with 8000 revs/min of revolving speed, precision measures
Supernatant liquor 2ml, with being dried with nitrogen, residue adds mass fraction to be the hexane solution of 0.02% 2,6-di-tert-butyl p-cresol
1ml makes to dissolve, as test solution.
3, vitamin D is lacked3Negative blank solution preparation:
Take the scarce vitamin D mixed in prescription ratio3Blank auxiliary, weight and contain vitamin D3The calcium carbonate of 30 μ g
D3Auxiliary material in particle is identical, about 32.4g, sets in 200ml brown measuring bottle, and the concentration that 50ml is added is 2, the 6- bis- of 0.2mg/ml
Dimethyl is sub- in the mixed solution of the dimethyl sulfoxide of Butylated Hydroxytoluene and the mixed solution of water, the dimethyl sulfoxide and water
Sulfone: the volume ratio of water is 10:2, then, sonic oscillation 15min, and constantly shake, keep ultrasonic water bath temperature to be no more than 30 DEG C,
The hexane solution 10ml for the 2,6-di-tert-butyl p-cresol that precision plus mass fraction are 0.02%, after shaking 15min, with 8000
Rev/min revolving speed be centrifuged 15min, precision measures supernatant liquor 2ml, and with being dried with nitrogen, residue adds mass fraction to be 0.02%
The hexane solution 1ml of 2,6-di-tert-butyl p-cresol make to dissolve, as scarce vitamin D3Negative blank solution.
Chromatogram is recorded as follows, and testing conditions are as follows:
Chromatographic column: 5 μm of 100A of silicagel column Inertsil SIL, 250 × 4.6mm；
The mixed liquor that mobile phase is made of the n-amyl alcohol that volume ratio is 3:997 and n-hexane；
Flow velocity is 2ml/min；
Detection wavelength is 254nm；
Sampling volume is 200 μ l.
In impurity reference substance mixed solution chromatogram, peak sequence is followed successively by provitamin D3, trans-vitamin D3, friction speed
Sterol D3, vitamin D3, tachysterol D3And vitamin D3Original, vitamin D in reference substance mixed solution chromatogram3Peak and front and back peak
Separating degree is all larger than 2.0, and the separating degree of each impurity peaks and adjacent peak is all larger than 1.0.Known impurities are in provitamin D3Behind peak
Appearance.
Lack vitamin D3Negative blank solution chromatogram the result shows that blank auxiliary measures related substance other impurities
There is interference, but to trans-vitamin D3With tachysterol D3It measures noiseless.
The every agreement that contracts a film or TV play to an actor or actress 1.62g of this product contains vitamin D3Only 1.5 μ g (1.5ppm), auxiliary material is more, vitamin D3Content is very low, is
The sensitivity requirement for meeting Related substances separation, needs to weigh a large amount of test samples, and accounts for about always in tablet containing a large amount of auxiliary materials
The 54% of amount, test sample preparation need to extract concentration and be measured.It extracts and is easy in concentration process by the impurity enriched in auxiliary material, warp
Repetition test shows that no effective ways, means removal auxiliary material appearance influence.
Therefore related substance method regulation: in test solution chromatogram, if any with trans-vitamin D3Peak retention time one
The chromatographic peak of cause must not cross 1.0% by external standard method with calculated by peak area；If any with tachysterol D3The consistent color of peak retention time
Spectral peak, peak area are not greater than the 1.0% of contrast solution main peak area, the tachysterol D3Peak and vitamin D3It is opposite to retain
Time is about 1.1.Verification test is the result shows that method is reasonable, controllable.
Two, the accuracy test of test solution preparation method:
Vitamin D is extracted to verify this method3Effect, verify extraction efficiency with the rate of recovery.According to recipe quantity in blank
The vitamin D of known quantity is added in auxiliary material3Powder.The vitamin D3Powder is bulk pharmaceutical chemicals vitamin D3Powder inclusion compound is not dimension life
Plain D3Reference substance is configured to test solution by test solution preparation method, is as a result indicated with the rate of recovery.
The accuracy test result of 1 test solution preparation method of table
Note: additional amount=sample weighting amount × 0.257%, 0.257% is vitamin D3Vitamin D in powder3Content；
The rate of recovery=measured amount/additional amount × 100%.
Vitamin D in this product recipe quantity3Powder only accounts for 0.04%, presses " drug standard analysis method verification guide principle "
It is required under (four general rules 9101 of Chinese Pharmacopoeia version in 2015) accuracy item, rate of recovery limit is 90%~108%.As a result table
Bright, the 100% concentration rate of recovery is repeated 6 times in 92%~100% range, meets rate of recovery bound requirements, average recovery rate
94.4%, RSD 2.83%, illustrating can be vitamin with the hexane solution 10ml of 0.02%2,6- di-tert-butyl p-cresol
D3It is extracted completely from extracting in solution.
Three, trans-vitamin D3The rate of recovery:
Trans-vitamin D3Recovery test is carried out according to 50%, 100%, the 150% of standard limits:
Precision weighs trans-vitamin D3Reference substance 10.28mg is set in 50ml measuring bottle, is added n-hexane to make to dissolve and is diluted to
Scale is trans-vitamin D3Reference substance mother liquor.Reference substance mother liquor is taken to be diluted to D containing trans-vitamin with ethyl alcohol3For 0.163 μ g/
The solution of ml is rate of recovery reference substance stock solution.
Lack vitamin D3Blank auxiliary 32.4g, set in 200ml brown measuring bottle, it is accurate respectively that rate of recovery reference substance is added
It is molten to be configured to rate of recovery test sample by test solution preparation method by stock solution 1ml, 2ml, 3ml (50%, 100%, 150%)
Liquid.Each parallel 3 parts of preparation of each concentration of the rate of recovery.
Precision weighs trans-vitamin D3Reference substance, which adds n-hexane dissolution and dilutes, is made trans-vitamin D3About 0.1 μ of concentration
The solution of g/ml is trans-vitamin D3Reference substance solution.
Accurate measure is trans-vitamin D respectively3Reference substance solution and each 200 μ l of above-mentioned test solution are measured, and are calculated
The rate of recovery simultaneously calculates RSD value.
2 trans-vitamin D3 recovery test result of table
Note: the rate of recovery=measured amount/additional amount × 100%.
The result shows that each concentration rate of recovery is between 93.5~107.5%, average recovery rate 101.6%, RSD is
4.5%, illustrate that this method accuracy is good.
Four, trans-vitamin D3Linear relationship is investigated:
Precision weighs trans-vitamin D3Reference substance adds n-hexane dilution that D containing trans-vitamin is made30.163 μ g/ml's
Solution shakes up, as linear stock solution.Precision measures linear stock solution 1ml, 2ml, 3ml, 4ml, 5ml, 6ml, 8ml, sets respectively
In 10ml measuring bottle；It is diluted to scale with n-hexane, is shaken up, the linear solvent of various concentration is made, as test solution.Respectively
Measurement.As shown in figure 5, with trans-vitamin D3Concentration C is abscissa, and peak area A is ordinate, obtains equation of linear regression: A=
198644C-212.11 R2=0.9999.
The result shows that trans-vitamin D3 concentration is within the scope of 0.016 μ of μ g/ml~0.130 g/ml, linear relationship is good.
Five, tachysterol D3The range of linearity is investigated:
Precision weighs tachysterol D3Reference substance adds n-hexane dilution that D containing tachysterol is made3For the solution of 0.170 μ g/ml, shake
It is even, as linear stock solution.Precision measures linear stock solution 2ml, 3ml, 4ml, 5ml, 6ml, 7ml, is set in 10ml measuring bottle respectively；
It is diluted to scale with n-hexane, is shaken up, the linear solvent of various concentration is made, as test solution.It measures respectively.Such as Fig. 6
It is shown, with tachysterol D3Concentration C is abscissa, and peak area A is ordinate, obtains equation of linear regression: A=200102C-
3842.2 R2=0.9998.
The result shows that tachysterol D3For concentration within the scope of 0.034 μ of μ g/ml~0.119 g/ml, linear relationship is good.
Six, specificity is tested:
The failure condition of 3 forced degradation of table test
4 failure test major degradants of table change list
As can be seen from the table, through strong acid, highly basic, oxidation, high temperature, exposure experiments to light, vitamin D3Degradation pathway is as follows:
(1) under illumination condition, trans-vitamin D3It obviously increases, bulk pharmaceutical chemicals vitamin D3Tachysterol D is detected in powder3；
(2) under hot conditions, provitamin D3It dramatically increases；
(3) under oxidation, strong acid, basic conditions, vitamin D3It is relatively stable.
Forced degradation experiments have shown that, the main degradation products of this product are provitamin D3, trans-vitamin D3And tachysterol
D3；Provitamin D3For effective component, according to this product characteristic, so it is trans- mainly to control known impurities in the quality standard of this product
Vitamin D3With tachysterol D3.Antioxidant 2,6- is added in the sample handling processes of Related substances separation and assay in this product
Di-tert-butyl p-cresol is protected from light, not higher than 30 DEG C of low-temperature treatments, protects vitamin D as far as possible3Degradation, processing method are closed
Reason.This product in process of production, should be also protected from light, low-temperature operation as far as possible.The storage condition of this product should seal, be protected from light, low temperature.
Seven, vitamin D3Detection limit, quantitative limit:
Precision weighs vitamin D3Appropriate reference substance is dissolved with isooctane, adds n-hexane to dilute step by step and test solution is made.
The result shows that: it is minimum detection limit by signal-to-noise ratio 3: 1, sample volume is 200 μ l, uses Single wavelength ultraviolet-visible point
Photodetector, lowest detection are limited to 4ng/ml, i.e. sample volume 0.8ng, about the 0.07% of test solution concentration.
5 vitamine D3 of table detection limit result
Precision weighs vitamin D3Appropriate reference substance is dissolved with isooctane, adds n-hexane to dilute step by step and test solution is made.
It is minimum quantitative limit by signal-to-noise ratio 10: 1, works as vitamin D3Concentration is 16ng/ml, and sample volume is 200 μ l, measures dimension
Raw element D3Average peak area is about 2848.3, and 10.3 times of noise about greatest around, parallel six parts of main peak retention time RSD
It is 0.30%, peak area RSD is 0.76%.The result shows that: minimum to be quantitatively limited to 16ng/ml, i.e. 3.2ng, about test sample is molten
The 0.27% of liquid concentration.
6 vitamine D3 quantitative limit result of table
Eight, trans-vitamin D3Detection limit, quantitative limit:
Precision weighs trans-vitamin D3Appropriate reference substance dilutes with n-hexane dissolution and step by step and test solution is made.
The result shows that: it is minimum detection limit by signal-to-noise ratio 3: 1, sample volume is 200 μ l, uses Single wavelength ultraviolet-visible point
Photodetector, lowest detection are limited to 4ng/ml (i.e. sample volume 0.8ng), about the 0.07% of test solution concentration.
| Retention time (minute) | Peak area | Detection limit | S/N | It is equivalent to test solution concentration |
| 21.613 | 444 | 0.8ng | 3.00 | 0.07% |
7 trans-vitamin D3 of table detection limit result
It is minimum quantitative limit by signal-to-noise ratio 10: 1, as trans-vitamin D3Concentration is 16ng/ml, and sample volume is 200 μ l, is surveyed
Obtain vitamin D3Average peak area is about 2454.5, and 10.2 times of noise about greatest around, when parallel six parts of main peak retains
Between RSD be 0.45%, peak area RSD be 1.31%.The result shows that: it is minimum to be quantitatively limited to 16ng/ml (i.e. sample volume 3.2ng),
About the 0.27% of test solution concentration.
8 trans-vitamin D3 quantitative limit result of table
The calcium carbonate D among the above3Chewable tablets, the entitled calcium carbonate D of national standard3Chewable tablets (II).
Above-described embodiment is the description of the invention, is not limitation of the invention, after any pair of simple transformation of the present invention
Scheme all belong to the scope of protection of the present invention.
Claims (3)
1. a kind of calcium carbonate D3The related substance detecting method of chewable tablets, it is characterised in that include the following steps:
A) it prepares test solution: being protected from light operation, take and be equivalent to containing vitamin D3The calcium carbonate D of 30 μ g3Chewable tablets is finely ground
Particle is set in brown measuring bottle, and the dimethyl for the 2,6-di-tert-butyl p-cresol that the concentration that 20~100ml is added is 0.2mg/ml is sub-
Dimethyl sulfoxide in the mixed solution of the mixed solution of sulfone and water, the dimethyl sulfoxide and water: the volume ratio of water is 10:2, is connect
, sonic oscillation, and constantly shake, precision adds mass fraction to be the hexane solution of 0.02% 2,6-di-tert-butyl p-cresol
5~25ml after shaking, is centrifuged, and precision measures 0.5~10ml of supernatant liquor, and with being dried with nitrogen, residue adds the mass fraction to be
0.5~2ml of hexane solution of 0.02% 2,6-di-tert-butyl p-cresol makes to dissolve, as test solution；
B) prepare contrast solution: precision measures 100 μ l of test solution, sets in 10ml measuring bottle, and adding mass fraction is 0.02%
The hexane solution of 2,6-di-tert-butyl p-cresol is diluted to scale, shakes up, as contrast solution；
C) prepare reference substance solution: another precision weighs trans-vitamin D3Reference substance with n-hexane dissolution and quantifies dilution and is made often
Containing about the solution of 0.1 μ g in 1ml, as reference substance solution；
D) liquid chromatographic detection: precision measures test solution, contrast solution and each 200 μ l of reference substance solution, is injected separately into liquid
Chromatography is recorded to 1.5 times of principal component peak retention time, in test solution chromatogram, if any with trans-vitamin D3
Retention time consistent chromatographic peak in peak must not cross 1.0% by external standard method with calculated by peak area, if any with tachysterol D3Peak retains
The chromatographic peak of time consistency, peak area are not greater than the 1.0% of contrast solution main peak area, the tachysterol D3Peak and dimension are given birth to
Plain D3Relative retention time is about 1.1.
2. a kind of calcium carbonate D as described in claim 13The related substance detecting method of chewable tablets, it is characterised in that: step a)
Described in time of sonic oscillation be 5~30min, and ultrasonic water bath temperature is kept to be no more than 30 DEG C, the shaking time for 5~
30min, the centrifugation time are 10~30min, and the revolving speed of centrifugation is 4000~12000rpm.
3. a kind of calcium carbonate D as described in claim 13The related substance detecting method of chewable tablets, it is characterised in that testing conditions
Include the following:
1. the stationary phase of chromatographic column is silica gel, the partial size of silicagel column is 5 μm, and column length is 150~250mm, internal diameter 4.6mm；
2. the mixed liquor that mobile phase is made of the n-amyl alcohol that volume ratio is 2.5~3.5:996.5~997.5 and n-hexane；
3. flow velocity is 1.0~2.5ml/min；
4. Detection wavelength is 254nm；
5. sampling volume is 50~250 μ l.
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| CN111239272A (en) * | 2020-01-21 | 2020-06-05 | 安士制药（中山）有限公司 | Detection of vitamin D3The method of preparing the impurity-related substance |
| CN114324648A (en) * | 2021-12-27 | 2022-04-12 | 广州朗圣药业有限公司 | Contains vitamin D3The high performance liquid detection method of related substances in the preparation and the preparation method of the test solution |
| CN115436544A (en) * | 2022-10-22 | 2022-12-06 | 河北御芝林生物科技有限公司 | Preparation method of vitamin D test solution and detection method of vitamin D in vitamin product |
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| CN110095489A (en) * | 2019-05-22 | 2019-08-06 | 北京悦康科创医药科技股份有限公司 | The method for quantitatively determining of impurity basic carbonate lanthanum in a kind of lanthanum carbonate chewable tablets |
| CN111239272A (en) * | 2020-01-21 | 2020-06-05 | 安士制药（中山）有限公司 | Detection of vitamin D3The method of preparing the impurity-related substance |
| CN114324648A (en) * | 2021-12-27 | 2022-04-12 | 广州朗圣药业有限公司 | Contains vitamin D3The high performance liquid detection method of related substances in the preparation and the preparation method of the test solution |
| CN115436544A (en) * | 2022-10-22 | 2022-12-06 | 河北御芝林生物科技有限公司 | Preparation method of vitamin D test solution and detection method of vitamin D in vitamin product |
| CN115436544B (en) * | 2022-10-22 | 2024-01-30 | 河北御芝林生物科技有限公司 | Preparation method of vitamin D test solution and detection method of vitamin D in vitamin product |
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