CN105044248A - Quantitative detection method of edetate disodium and sodium pyrosulfite in Shenqifuzheng injection - Google Patents
Quantitative detection method of edetate disodium and sodium pyrosulfite in Shenqifuzheng injection Download PDFInfo
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Abstract
The invention provides a quantitative detection method for quantitatively analyzing edetate disodium and sodium pyrosulfite in a Shenqifuzheng injection. The quantitative detection method comprises the following steps: preparing edetate disodium and sodium pyrosulfite reference solutions; preparing a Shenqifuzheng injection test article solution; quantitatively analyzing the reference solutions and the test article solution by adopting ion chromatography; according to the ion chromatographic peak areas of EDTA<2-> as well as SO3<2-> and SO4<2-> in ion chromatograms of reference substances and a sample and according to the principle of conservation of the element S in the solutions, respectively converting the contents of edetate disodium and sodium pyrosulfite in the sample according to the mole ratio of edetate disodium to EDTA<2->, the mole ratio of sodium pyrosulfite to SO3<2->, the mole ratio of sodium pyrosulfite to SO4<2-> and the molecular weights of the substances.
Description
Technical field
The present invention relates to a kind of method for ginseng and astragalus injection for strengthening body security control and application, specifically by setting up the method that the chromatography of ions detects the additives natrium adetate added in ginseng and astragalus injection for strengthening body and sodium pyrosulfite and applies, belong to Pharmaceutical Analysis technology and security control field.
Background technology
Ginseng and astragalus injection for strengthening body is national Chinese medicine protection kind; protection kind number: ZYB2072004073; it is the Chinese medicine infusion solutions be made up through extraction of the Radix Astragali and Radix Codonopsis; for the supplemental treatment of qi deficiency lung cancer, cancer of the stomach; the immunologic function of body can be improved; and can Cardial or cerebral vascular diseases be treated, have strengthen the body resistance to consolidate the constitution, beneficial gas qi-restoratives, effect promoting blood circulation and removing blood stasis.
Ginseng and astragalus injection for strengthening body complicated component, according to open source information in ZL201210436493.4, in its finger-print, only characteristic peak just has 18 more than; According to ZL201310008395.5, the composition that ginseng and astragalus injection for strengthening body identifies has calycosin-7-O-β-D-Glucose glycosides, different dimpling sword-like leave Sha alcohol-7,2 '-two-O-glucoside, biochanin-7-glucoside, 9,10-dimethoxy red sandalwood alkane-3-O-xylose glucose glycosides, Astragaloside IV, 5 hydroxymethyl furfural etc., many known and unknown compositions bring great difficulty to the quality control of ginseng and astragalus injection for strengthening body.In order to keep controllability and the stability of parenteral solution quality, the method for the high accuracy analysis such as infrared spectrum, nuclear magnetic resonance, high performance liquid chromatography is applied to monitoring the larger water soluble ingredient in S peak (Calycosin-7-O-BETA-D-glucoside) and polarity in ginseng and astragalus injection for strengthening body, Astragaloside content, its negative correlation composition, saponin component etc. all in succession.Even if the analyzing detecting method of numerous advanced person is used for ginseng and astragalus injection for strengthening body quality control, but in order to check erroneous ideas at the outset, increase clinical drug safety, the research for ginseng and astragalus injection for strengthening body quality control is never interrupted.
While assorted composition brings great difficulty to the quality control of ginseng and astragalus injection for strengthening body, also cause certain puzzlement to production.When preparing intravenously administrable transfusion, general use rustless steel container and pipeline, under heating state, after parenteral solution contacted with long periods such as canister, pipeline, filters, the component of parenteral solution can be combined with materials such as metallic ions, generate coloured metal composite, solution colour is caused to deepen, react to prevent main ingredient and metallic ion, reduce solution changes color, with the addition of appropriate metal chelating agent natrium adetate and antioxidant sodium pyrosulfite in this product, addition is approximately 0.2g/L and 0.5g/L.
There are some researches show now, natrium adetate can become solvable complex compound to cause the minimizing of calcium with calcium binding, use natrium adetate that blood calcium can be caused to decline in intravenous formulations, cause blood calcium too low if add excessive meeting, feel sick, headache, urgent urination, the bad reaction such as blood coagulability reduction; Have bibliographical information: if human body takes in natrium adetate in a large number, natrium adetate can form water soluble chelate compound with the calcium in blood and bone, is excreted, and causes low blood calcium or bone calcium loss, causes twitching even dead.In addition, sodium pyrosulfite is in the solution with SO
3 2-and SO
4 2-form exist, store of a specified duration, also can discharge SO
2.SO
2there is obvious spread effect to skin, mucous membrane, conjunctiva, bronchitis symptom can be caused; Its hyposulfite also can cause allergy.The applicable crowd of ginseng and astragalus injection for strengthening body is qi deficiency lung cancer, patients with gastric cancer, and physical function is weak, immunity degradation, more easily produces the bad reaction such as allergy, headache, therefore needs stricter control natrium adetate and sodium pyrosulfite use amount.Although with the addition of metal chelating agent natrium adetate and antioxidant sodium pyrosulfite in ginseng and astragalus injection for strengthening body, be aimed at additives and not yet set up disclosed method of quality control.The uncertain factor such as personnel's emotional instability, may cause the deviation of inventory, bring quality and potential safety hazard in process of production.In order to ensure the safety of clinical application, need to set up method of quality control to natrium adetate and sodium pyrosulfite.
Summary of the invention
The invention provides a kind of method that chromatography of ions quantitative analysis controls additives natrium adetate and pyrosulfurous acid sodium content in ginseng and astragalus injection for strengthening body, be specifically related to the quantitative detecting method of natrium adetate and sodium pyrosulfite in a kind of ginseng and astragalus injection for strengthening body.
Another object of the present invention is to provide the application of above-mentioned quantitative detecting method.
In some documents, in drug injection liquid during micro ion sulfate by ion chromatography, parenteral solution is directly injected in ion chromatographic column and analyzes.The complicated component of ginseng and astragalus injection for strengthening body, as stated in the Background Art, wherein containing all multicomponents such as amino acid, carbohydrate (mainly monose and oligosaccharides), organic acid, sodium chloride, various different chemical substance reaches more than 18 kinds, and the content of natrium adetate and sodium pyrosulfite 2 kinds of additives is low, through overtesting, find parenteral solution directly to inject in ion chromatographic column, the chlorion peak area that result chromatogram shows is too high, accounts for more than 95% of whole Component peak area; Chromatographic column post effect declines very fast simultaneously, and retention time fluctuation is large, causes the spectrogram obtained to understand, natrium adetate and sodium pyrosulfite cannot be detected at all.
In order to overcome the above problems, inventor gropes through many-sided, after finding sample to dilute, significantly can reduce the peak area of chlorion, but the ginseng and astragalus injection for strengthening body after dilution in the detection chromatographic column post effect still exists and declines fast, and retention time fluctuates large problem.
In documents and materials disclosed in, when ZL201310756866.0 magnetic nuclear resonance method carries out quality control to ginseng and astragalus injection for strengthening body, ginseng and astragalus injection for strengthening body have passed through frozen dried; ZL201310008395.5, ginseng and astragalus injection for strengthening body processes through 0.45 μm of miillpore filter filter; ZL201210436493.4 adopts 0.22um miillpore filter to filter and processes; In ZL200710136382.0, filter through macroreticular resin, the treatment steps such as extraction.Process means in open source literature are applied in the present invention by inventor, all cannot solve the technical matters that the decline of post effect is fast.
Through arduous test, the ginseng and astragalus injection for strengthening body that our pleasantly surprised discovery uses the process of C18 post diluted, the interference of its chlorion peak area is eliminated, and chromatographic column post effect does not obviously decline, the fluctuation of retention time is controlled, natrium adetate and sodium pyrosulfite can be detected by accurate quantification.
The quantitative detecting method of natrium adetate and sodium pyrosulfite in a kind of ginseng and astragalus injection for strengthening body of the present invention, comprises the following steps:
(1) with the EDTA of natrium adetate and sodium pyrosulfite in sulfate by ion chromatography ginseng and astragalus injection for strengthening body
2-, SO
3 2-, SO
4 2-ion concentration;
(2) calculating of natrium adetate and sodium pyrosulfite:
The calculating of natrium adetate: according to EDTA described in step (1)
2-concentration, according to natrium adetate and EDTA
2-the mol ratio of 1: 1, converts out the concentration of natrium adetate in solution;
The calculating of sodium pyrosulfite: 1. by areas of peak normalization method, utilizes and draws Na
2s
2o
5during reference substance typical curve variable concentrations Working Control solution in SO
3 2-and SO
4 2-peak area, calculate Na
2s
2o
5sO in solution
3 2-and SO
4 2-ratio; 2. according to Na
2s
2o
5in reference substance solution, SO
3 2-and SO
4 2-ratio and S element conservation, according to Na
2s
2o
5respectively with SO
3 2-and SO
4 2-mol ratio, converted by the molecular weight of three, draw SO respectively
3 2-and SO
4 2-typical curve; 3. SO in solution per sample
3 2-and SO
4 2-peak area, substitute into SO respectively
3 2-and SO
4 2-typical curve, calculate SO
3 2-and SO
4 2-concentration, then convert out SO according to molecular weight
3 2-and SO
4 2-volumetric molar concentration; 4. according to S element conservation in solution, according to SO
3 2-and SO
4 2-volumetric molar concentration, calculate Na
2s
2o
5volumetric molar concentration, and then calculate Na in sample according to molecular weight
2s
2o
5concentration.
Ginseng and astragalus injection for strengthening body described in step (1), first by C18 pillar purifying, then after eluent dilution 50-400 times, then passes through ion chromatographic column.
Ginseng and astragalus injection for strengthening body described in step (1), first by C18 pillar purifying, then after eluent dilution 100-200 times, then passes through ion chromatographic column.
Ginseng and astragalus injection for strengthening body described in step (1) first by C18 pillar purifying, after then eluent dilutes 200 times, then passes through ion chromatographic column.
Also comprise the preparation of reference substance solution in described step (1), get natrium adetate respectively, sodium pyrosulfite reference substance is appropriate, accurately weighed, add water and make every 1mL respectively containing the solution of natrium adetate, sodium pyrosulfite 1 μ g.
The chromatographic chromatographic condition of described step (1) intermediate ion is: chromatographic column is IonPacAS11-HC (4 × 250mm), eluent concentration is the potassium hydroxide solution of 0 ~ 30min15mmol/L, electric conductivity detector, flow velocity is 1mL/min, and sample size is 25 μ L.
The control method of natrium adetate provided by the invention and sodium pyrosulfite can be applied to the mensuration of additives in ginseng and astragalus injection for strengthening body, can effectively evaluate the security of ginseng and astragalus injection for strengthening body.
Compared with prior art, the present invention has following beneficial effect:
In ginseng and astragalus injection for strengthening body quality standard and relevant research data thereof, not yet its additives natrium adetate and sodium pyrosulfite are controlled, and excessive natrium adetate and sodium pyrosulfite have damage to human body, this kind special is intravenous injection, risk need be evaluated the security of additives compared with great ， Qi and control.Therefore the inventive method sets up the technical standard of natrium adetate and sodium pyrosulfite in sulfate by ion chromatography ginseng and astragalus injection for strengthening body, by quantitative test EDTA
2-and SO
3 2-, 5O
4 2-, fast and effeciently can monitor the consumption of medicine additives, except except the working specification feeding intake source strict control personnel, monitor the approach of medicine additives consumption after additionally providing a kind of feeding intake, two ore control, safety of ensuring drug quality.The present invention simultaneously can also measure EDTA by real-time quantitative
2-, SO
3 2-and SO
4 2-amount, for the surplus of natrium adetate and sodium pyrosulfite in accurate Calculation ginseng and astragalus injection for strengthening body product storage, thus whether the inventory of the burnt natrium adetate of accurate evaluation and sodium sulphite is reasonable, the inventory of final precision adjustment natrium adetate and sodium pyrosulfite, reach the result controlled by most scientific inventory, most effective mass to greatest extent, optimize the use of medicine additives, ensure drug safety.In addition, Simultaneously test SO is passed through in the present invention
3 2-and SO
4 2-in calculation sample, the method for pyrosulfurous acid sodium content has certain advance, its stability and reappearance all better, can be applied to the detection of other preparations.
Accompanying drawing explanation
Fig. 1 is natrium adetate reference substance chromatography of ions figure;
Fig. 2 is sodium pyrosulfite reference substance chromatography of ions figure;
Fig. 3 is the chromatography of ions figure of ginseng and astragalus injection for strengthening body sample;
Fig. 4 is the chromatography of ions figure of pure water;
Fig. 5 is natrium adetate canonical plotting;
Fig. 6 is inferior sulfate radical canonical plotting;
Fig. 7 is sulfate radical canonical plotting;
Fig. 8 is the chromatography of ions figure of the different extension rate of ginseng and astragalus injection for strengthening body;
The chromatography of ions figure of Fig. 9 to be ion chromatographic column be Biobasic;
The chromatography of ions figure of Figure 10 to be ion chromatographic column be AS11-HC;
The chromatography of ions figure of Figure 11 to be ion chromatographic column eluent concentration be 15mMol/L;
The chromatography of ions figure of Figure 12 to be ion chromatographic column eluent concentration be 13mMol/L;
The chromatography of ions figure of Figure 13 to be ion chromatographic column eluent concentration be 11.5mMol/L;
The chromatography of ions figure of Figure 14 to be ion chromatographic column eluent concentration be 10mMol/L;
Figure 15 is the chromatography of ions figure of sample pre-treatments and sample injection time difference.
Embodiment
Technical scheme of the present invention is further illustrated below by way of specific embodiment.
Embodiment 1
1 instrument and reagent
1.1 instruments: ion chromatograph: DIONEXICS-2000 (Dai An company); Chromatographic column: IonPacAS11-HC (4 × 250mm) (Dai An company); Guard column: IonPacAH11-HC (4 × 50mm) (Dai An company); Detecting device: electric conductivity detector (Dai An company); Drip washing flow container: EGCIIKOH (090581489019).Millipore pure water instrument.
1.2 reagents: natrium adetate reference substance (lot number: 20100311, Hangzhou Li Ren pharmaceutcal corporation, Ltd); Sodium pyrosulfite reference substance (lot number: 20100301, Hunan Er-kang Pharmaceutical Co., Ltd.).Sep-PakCartridgesVacC183cc pillar (Waters).Ginseng and astragalus injection for strengthening body, is provided by Livzon Group Limin Pharmaceutical Factory.In experiment, agents useful for same acetonitrile, formic acid are chromatographically pure, and water is ultrapure water.
2 methods and result
The preparation of 2.1 need testing solutions: precision measures ginseng and astragalus injection for strengthening body 1mL, by C18 pillar purifying, uses deionized water wash-out, constant volume 10mL measuring bottle, then precision measures 2.5mL in 50mL measuring bottle, and constant volume, to obtain final product.
The preparation of 2.2 reference substance solution: accurately weighed natrium adetate, sodium pyrosulfite reference substance 0.01140g, 0.01168g are in 100mL measuring bottle respectively, are dissolved in water and are diluted to scale, respectively as natrium adetate, sodium pyrosulfite reference substance storing solution.
2.3 chromatographic conditions: chromatographic column is IonPacAS11-HC (4 × 250mm), and eluent concentration is the potassium hydroxide solution of 0 ~ 30min15mmol/L, electric conductivity detector, and flow velocity is 1mL/min, sample size is 25 μ L.
2.4 linear relationship
2.4.1 the linear relationship of natrium adetate
Respectively natrium adetate reference substance storing solution is diluted, a series of solution of preparation typical curve: 4.56,3.42,2.28,1.14,0.57 μ g/mL, sample introduction analysis under above-mentioned chromatographic condition, record reference substance peak area.With reference substance peak area for ordinate, concentration is that horizontal ordinate draws reference substance typical curve: y=0.039x-0.0087, r=0.9990, result shows that natrium adetate is good in the concentration range internal linear relation of 0.57 ~ 4.56 μ g/mL.
2.4.2 the linear relationship of sodium pyrosulfite
Due to Na
2s
2o
5with SO in water
3 2-and SO
4 2-form exist, adopt measure SO respectively
3 2-and SO
4 2-method, convert out Na
2s
2o
5content (S conservation).
Na
2s
2o
5+ H
2o=2NaHSO
3(sodium pyrosulfite water suction)
2NaHSO
3+ O
2=2NaHSO
4(sodium bisulfite oxidation)
The niter cake of oxidized generation also can react with the sodium pyrosulfite do not absorbed water or sodium bisulfite:
2NaHSO
4+Na
2S
2O
5＝2Na
2SO
4+2SO
2+H
2O
NaHSO
3+NaHSO
4＝Na
2SO
4+SO
2+H
2O
Respectively sodium pyrosulfite storing solution is diluted, a series of solution of preparation typical curve: 4.672,3.504,2.336,1.168,0.584 μ g/mL, respectively sample introduction 25 μ L, record reference substance peak area.First, by areas of peak normalization method, calculate Na
2s
2o
5in solution, SO
3 2-and SO
4 2-ratio (see table 1):
Table 1SO
3 2-and SO
4 2-at Na
2s
2o
5distribution in solution
According to Na
2s
2o
5in solution, SO
3 2-and SO
4 2-ratio and S element conservation, draw SO respectively
3 2-and SO
4 2-typical curve:
1. SO
3 2-typical curve: y=0.112x-0.0089, r=0.9985 (table 2).
Table 2SO
3 2-typical curve
| Working curve (μ g/ml) | Peak area |
| 2.805 | 0.313 |
| 2.334 | 0.246 |
| 1.497 | 0.153 |
| 0.775 | 0.078 |
| 0.381 | 0.038 |
2. SO
4 2-typical curve: y=0.0942x-0.0031, r=0.9992 (table 3).
Table 3SO
4 2-typical curve
| Working curve (μ g/ml) | Peak area |
| 1.355 | 0.126 |
| 0.740 | 0.065 |
| 0.564 | 0.048 |
| 0.250 | 0.021 |
| 0.132 | 0.011 |
2.5 precision tests: get ginseng and astragalus injection for strengthening body (lot number: 0910499), prepare by the preparation method of need testing solution, continuous sample introduction 6 times, measures the content of natrium adetate and sodium pyrosulfite, and result shows precision good (see table 4).
Table 4 precision test
2.6 replica tests: get with a collection of ginseng and astragalus injection for strengthening body that (lot number: 1001015), totally 6 parts, respectively sample introduction, measures the content of natrium adetate and sodium pyrosulfite, and result shows this law repeatability good (see table 5).
Table 5 replica test
2.7 recovery tests: get with a collection of ginseng and astragalus injection for strengthening body (lot number: 1001015) 1mL, totally 6 parts, according to repeatability and the linear theoretical content calculating natrium adetate and sodium pyrosulfite, add natrium adetate and the sodium pyrosulfite reference substance of equivalent, dilute one times, actual measured value according to natrium adetate and sodium pyrosulfite calculates the recovery, result shows that the recovery of natrium adetate and sodium pyrosulfite is all between 90% ~ 110%, this method accuracy good (see table 6, table 7).
The preparation of recovery reference substance solution: precision takes natrium adetate and sodium pyrosulfite 0.02163g, 0.05145g in 100mL measuring bottle respectively, be mixed with the mixing reference substance solution of natrium adetate and sodium pyrosulfite, the more accurate 1mL that draws adds in test sample.
The recovery of table 6 natrium adetate is investigated
The recovery of table 7 sodium pyrosulfite is investigated
2.8 stability
2.8.1 sample stability is investigated
(lot number: 1001015), respectively at 0,2,4,8,12 hour sample introduction, the peak area of record natrium adetate and sodium pyrosulfite, result showed that sample was at 12 hours internal stabilities good (see table 8) to get ginseng and astragalus injection for strengthening body.
Table 8 study on the stability
2.8.2 sodium pyrosulfite study on the stability
Due to Na
2s
2o
5in aqueous with SO
3 2-and SO
4 2-form exist, and SO
3 2reaction can generate SO further
2, be necessary to investigate its stability.Precision takes Na
2s
2o
50.01189g, being mixed with concentration is 1.189 μ g/mL solution, respectively at 0,2,4,6,8,10,12 hour sample introduction, record SO
3 2-and SO
4 2-peak area.Result shows that sodium pyrosulfite two ions were in aqueous at 12 hours internal stabilities good (see table 9).
Table 9Na
2s
2o
5study on the stability
Natrium adetate and pyrosulfurous acid sodium determination application example in 2.9 ginseng and astragalus injection for strengthening body
The chromatography of ions applying above-mentioned foundation measures natrium adetate in ginseng and astragalus injection for strengthening body and sodium pyrosulfite, the content of additives can be analyzed quickly and accurately, the security of ginseng and astragalus injection for strengthening body is controlled, has certain directive significance to the consumption of enterprises adjustment additives simultaneously.Part batch measurement result in table 10, result show, in sample, natrium adetate content is between 0.163 ~ 0.198mg/mL, basically identical with inventory (0.2g to 1000ml); The content of sodium pyrosulfite is through converting between 0.445 ~ 0.537mg/mL, basically identical with inventory (0.5g to 1000ml).Result shows, the additives content in the ginseng and astragalus injection for strengthening body that detects of application the method and its inventory basically identical, can be used for the evaluation of this kind security.
Natrium adetate and sodium pyrosulfite measurement result in table 10 sample segment
Therefore, natrium adetate and sodium pyrosulfite in application ion-chromatographic determination ginseng and astragalus injection for strengthening body, effectively can control the security of this product, ensure the safety and stability of this kind clinical application.
The screening of embodiment 2 ginseng and astragalus injection for strengthening body extension rate
The preparation of need testing solution:
Need testing solution 1: dilute 10 times
Precision measures ginseng and astragalus injection for strengthening body 1mL, by C18 pillar purifying, uses deionized water wash-out, and constant volume 10mL measuring bottle, constant volume, to obtain final product.
Need testing solution 2: dilute 20 times
Precision measures ginseng and astragalus injection for strengthening body 1mL, by C18 pillar purifying, uses deionized water wash-out, constant volume 10mL measuring bottle, then precision measures 2.5mL in 5mL measuring bottle, and constant volume, to obtain final product.
Need testing solution 3: dilute 50 times
Precision measures ginseng and astragalus injection for strengthening body 1mL, by C18 pillar purifying, uses deionized water wash-out, constant volume 10mL measuring bottle, then precision measures 10mL in 50mL measuring bottle, and constant volume, to obtain final product.
Need testing solution 4: dilute 100 times
Precision measures ginseng and astragalus injection for strengthening body 1mL, by C18 pillar purifying, uses deionized water wash-out, constant volume 10mL measuring bottle, then precision measures 5mL in 50mL measuring bottle, and constant volume, to obtain final product.
Need testing solution 5: dilute 200 times
Precision measures ginseng and astragalus injection for strengthening body 1mL, by C18 pillar purifying, uses deionized water wash-out, constant volume 10mL measuring bottle, then precision measures 2.5mL in 50mL measuring bottle, and constant volume, to obtain final product.
Need testing solution 6: dilute 400 times
Precision measures ginseng and astragalus injection for strengthening body 1mL, by C18 pillar purifying, uses deionized water wash-out, constant volume 10mL measuring bottle, then precision measures 2.5mL in 100mL measuring bottle, and constant volume, to obtain final product.
Other experimental implementation scheme is with reference to described in embodiment 1, and experimental result is shown in Fig. 8 and as following table 11:
Table 11
| Inferior sulfate radical area | Sulfate radical area | Inferior sulfate radical/sulfate radical | |
| Need testing solution 6 | 4.225 | 2.071 | 2.04 |
| Need testing solution 5 | 9.963 | 4.492 | 2.22 |
| Need testing solution 4 | 20.034 | 9.037 | 2.22 |
| Need testing solution 3 | 41.994 | 18.656 | 2.25 |
| Need testing solution 2 | 108.105 | 47.352 | 2.28 |
| Need testing solution 1 | 221.663 | 94.701 | 2.34 |
As seen from the figure, along with extension rate strengthens, the response of chlorion obviously reduces, and effectively reduces the pollution to system; , consider according to instrument signal to noise ratio, inferior sulfate radical and sulfate radical ratio stability meanwhile, the peak area of inferior sulfate radical about 10, the peak area of sulfate radical about 5, ratio is advisable about 2.2.Therefore dilution 200 times is selected.
Embodiment 3 chromatographic column is selected
Compare AS11-HC and Biobasic two kinds of ion chromatographic columns, experiment condition is with reference to described in embodiment 1, and experimental result is as chromatogram 9 and 10.
AS11-HC figure baseline is steady, and degree of separation comparatively Biobasic is schemed.Therefore AS11-HC ion chromatographic column is selected.
Embodiment 4: the selection of ion chromatographic column eluent concentration
Eluent concentration examines the potassium hydroxide solution of 15mMol/L, 13mMol/L, 11.5mMol/L, 10mMol/L respectively, and other experiment condition carries out according to embodiment 1.
Leacheate variable concentrations chromatogram is shown in 11-14.
According to chromatogram, be that the potassium hydroxide solution of 15mMol/L with 13mMol/L is compared with leacheate when leacheate is the potassium hydroxide solution of 11.5mMol/L with 10mMol/L, it is more steady that inferior sulfate radical goes out the baseline before peak, and the potassium hydroxide solution of 11.5mMol/L and 10mMol/L is more suitable for as leacheate.
Compared with the potassium hydroxide solution being 10mMol/L with leacheate when leacheate is the potassium hydroxide solution of 11.5mMol/L, appearance time is shorter, and in order to shorten analysis time, the potassium hydroxide solution of preferred 11.5mMol/L is as leacheate.
Embodiment 5: sample pre-treatments and sample injection time
Because inferior sulfate radical is unstable, oxidizable, the display of sample stability examination situation, sample introduction after 8 hours placed by sample, and result has comparatively significant change, and thus after process, sample should complete mensuration in 6 hours.Should anticipate during processing sample the clean situation of cut-back tank, thinned water should use ultrapure water in preparation 2 hours (or with front proper method deoxidation treatment) simultaneously.
Table 12
Embodiment 6: the screening of ginseng and astragalus injection for strengthening body pre-treatment step
Direct-injection technique: result chlorion peak area is too high, accounts for more than 95% of whole Component peak area; Chromatographic column post effect declines very fast simultaneously, and retention time fluctuation is large.
Dilution sampling system (but C18 post): investigated extension rate, determine that extension rate is 200, the interference of result chlorion reduces greatly, but chromatographic column post effect still declines obviously.
Dilute 200 times after 0.45 μm of filtering with microporous membrane: the interference of chlorion reduces greatly, but chromatographic column post effect still declines obviously.
Dilution 200 times after after 0.22um filtering with microporous membrane: the interference of chlorion reduces greatly, but chromatographic column post effect still declines obviously.
Dilute 200 times after AB-8 macroreticular resin filtration treatment: the interference of chlorion reduces greatly, the decline of chromatographic column post effect improves, but retention time still fluctuates, and can not meet analysis demand.
Dilution 200 times after C18 post filters: the interference of chlorion reduces greatly, the decline of chromatographic column post effect improves, and retention time fluctuation is less, can meet analysis demand.
To sum up, preferred C18 post is as pretreated means.
Claims (6)
1. the quantitative detecting method of natrium adetate and sodium pyrosulfite in ginseng and astragalus injection for strengthening body, comprises the following steps:
(1) with the EDTA of natrium adetate and sodium pyrosulfite in sulfate by ion chromatography ginseng and astragalus injection for strengthening body
2-, SO
3 2-, SO
4 2-ion concentration;
(2) calculating of natrium adetate and sodium pyrosulfite:
The calculating of natrium adetate: according to the concentration of EDTA2-described in step (1), according to natrium adetate and EDTA2-1: 1 mol ratio, convert out the concentration of natrium adetate in solution;
The calculating of sodium pyrosulfite: 1. by areas of peak normalization method, utilizes and draws Na
2s
2o
5during reference substance typical curve variable concentrations Working Control solution in SO
3 2-peak area with SO42-, calculates Na
2s
2o
5sO in solution
3 2-and SO
4 2-ratio; 2. according to Na
2s
2o
5in reference substance solution, SO
3 2-and SO
4 2-ratio and S element conservation, according to Na
2s
2o
5respectively with SO
3 2-and SO
4 2-mol ratio, converted by the molecular weight of three, draw SO respectively
3 2-and SO
4 2-typical curve; 3. SO in solution per sample
3 2-and SO
4 2-peak area, substitute into SO respectively
3 2-and SO
4 2-typical curve, calculate SO
3 2-and SO
4 2-concentration, then convert out SO according to molecular weight
3 2-and SO
4 2-volumetric molar concentration; 4. according to S element conservation in solution, according to SO
3 2-and SO
4 2-volumetric molar concentration, calculate Na
2s
2o
5volumetric molar concentration, and then calculate Na in sample according to molecular weight
2s
2o
5concentration;
Ginseng and astragalus injection for strengthening body described in step (1), first by C18 pillar purifying, then after eluent dilution 50-400 times, then passes through ion chromatographic column.
2. the quantitative detecting method of natrium adetate and sodium pyrosulfite in a kind of ginseng and astragalus injection for strengthening body as claimed in claim 1, it is characterized in that ginseng and astragalus injection for strengthening body described in step (1) first by C18 pillar purifying, then after eluent dilution 100-200 times, then ion chromatographic column is passed through.
3. the quantitative detecting method of natrium adetate and sodium pyrosulfite in a kind of ginseng and astragalus injection for strengthening body according to claim 2, ginseng and astragalus injection for strengthening body described in step (1) is first by C18 pillar purifying, then after eluent dilutes 200 times, then ion chromatographic column is passed through.
4. the quantitative detecting method of natrium adetate and sodium pyrosulfite in a kind of ginseng and astragalus injection for strengthening body as claimed in claim 1, it is characterized in that the preparation also comprising reference substance solution in described step (1), get natrium adetate respectively, sodium pyrosulfite reference substance is appropriate, accurately weighed, add water and make every 1mL respectively containing the solution of natrium adetate, sodium pyrosulfite 1 μ g.
5. the quantitative detecting method of natrium adetate and sodium pyrosulfite in a kind of ginseng and astragalus injection for strengthening body as claimed in claim 1, it is characterized in that the chromatographic chromatographic condition of described step (1) intermediate ion is: chromatographic column is AS11-HC (4 × 250mm), eluent concentration is the potassium hydroxide solution of 0 ~ 30min10-15mMol/L, electric conductivity detector, flow velocity is 1mL/min, and sample size is 25 μ L.
6. the quantitative detecting method of natrium adetate and sodium pyrosulfite in a kind of ginseng and astragalus injection for strengthening body as claimed in claim 5, it is characterized in that the chromatographic chromatographic condition of described step (1) intermediate ion is: chromatographic column is AS11-HC (4 × 250mm), eluent concentration is the potassium hydroxide solution of 0 ~ 30min11.5mMol/L, electric conductivity detector, flow velocity is 1mL/min, and sample size is 25 μ L.
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