CN103175930B - A kind of HPLC analytical method measuring sodium sulphite content - Google Patents
A kind of HPLC analytical method measuring sodium sulphite content Download PDFInfo
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Abstract
The invention discloses a kind of method adopting high effective liquid chromatography for measuring sodium sulphite content, it is filling agent that described method comprises with octadecylsilane chemically bonded silica, to be added with the phosphate buffer-methyl alcohol of 4-butyl ammonium hydrogen sulfate for mobile phase, the volume ratio of damping fluid-methyl alcohol is 90:10 ~ 70:30; Determined wavelength is 214 ± 5nm; Flow velocity is 0.5ml/min ~ 1.2ml/min.Adopt the method ion similar to sulfite ion and other effectively can be separated and energy accurate quantitative analysis.The specificity of this method is strong, and precision is good, and accuracy is high, can measure the content of sodium sulphite rapidly and accurately.
Description
Technical field
The present invention relates to the detection method of medicine, relate in particular to a kind of HPLC analytical method measuring sodium sulphite content.
Background technology
Sodium sulphite has reductibility, can be used as antioxidant and is widely used in parenteral solution.Because sodium sulphite has certain toxic and side effect to human body, in recent years, more and more stricter to the control of this kind antioxidant consumption in injection, be not the requirement of limit, but require its content of Accurate Determining.The method of current mensuration sodium sulphite content has following three classes: (1) utilizes its reductibility usually, carries out titration with iodine titration solution and sodium thiosulfate; As measured sodium sulphite by the method, then in sample, other composition must not have reductibility.(2) utilize sodium sulphite and acid reaction, the sulphuric dioxide of generation can make the character that acid magenta is faded carry out quantitatively sodium sulphite, but the sensitivity of the method is not high.(3) utilize itself and complexing agent complexes to develop the color, measure with UV-VIS spectrophotometry; As measured sodium sulphite in this approach, other composition must not develop the color with complexing agent complexes, and the stability of solution of complex compound colour developing is poor.
The deficiency of these three class methods is embodied in: (1) sensitivity is low; (2) specificity is poor, when there is the material close with its character in product, cannot measure the content of sodium sulphite.As sodium thiosulfate has the character similar to sodium sulphite.Existing method can not measure the content of sodium thiosulfate inj sulfite sodium quickly and accurately.Therefore, need to find a kind of new analytical approach to measure the content of sodium sulphite.It is high that high performance liquid chromatography has separation efficiency, and selectivity is good, and detection sensitivity is high, operation automation, the advantages such as applied range, can make up the deficiency of said method with high efficiency liquid phase chromatographic analysis method.But sulfite ion in C18, C8 chromatographic column substantially without reserve, cannot separate with other ions such as thiosulfate ions, the method measuring sodium sulphite content with high efficiency liquid phase chromatographic analysis method has had not yet to see disclosed report, therefore need to set up a kind of can the method for rapid and accurate determination sodium sulphite content.
Summary of the invention
The object of the invention is to set up a kind of can mensuration fast and accurately in the HPLC analytical method, particularly sample of sodium sulphite content containing the method measuring the content of sodium sulphite during the material similar to sodium sulphite.To make up the deficiencies in the prior art.
In order to achieve the above object, technical scheme of the present invention is as follows:
Measure a HPLC analytical method for sodium sulphite content, adopt reversed-phased high performace liquid chromatographic, its concrete chromatographic condition is as follows:
Chromatographic column: the chromatographic column taking octadecylsilane chemically bonded silica as filling agent, column packing particle diameter is 3.5 μm ~ 5 μm, and column length is 150mm ~ 250mm.
Mobile phase: methanol-water phase (containing 2.0g ~ 2.5g sodium hydrogen phosphate and 0.50g ~ 1.0g 4-butyl ammonium hydrogen sulfate in 750ml aqueous phase, adjusting pH to 8.5 ~ 9.5 with 1mol/L sodium hydroxide solution), the volume ratio of methanol-water phase is 10:90 ~ 30:70.
Flow velocity: 0.5ml/min ~ 1.2ml/min.
Column temperature: 20 DEG C ~ 30 DEG C.
Determined wavelength: 214 ± 5nm.
Sample size: 5 μ l ~ 20 μ l.
Preferred color of choice spectral condition: the chromatographic column taking octadecylsilane chemically bonded silica as filling agent; Be mobile phase with methanol-water phase (containing 2.2g ~ 2.5g sodium hydrogen phosphate and 0.70g ~ 0.85g 4-butyl ammonium hydrogen sulfate in 750ml aqueous phase, adjusting pH to 9.0 with 1mol/L sodium hydroxide solution), the volume ratio of methanol-water phase is 25:75; Flow velocity is 1.0ml/min; Determined wavelength is 214nm; Sample size is 5 μ l.
The preparation of sample solution: it is appropriate that precision takes anhydrous sodium sulfite, puts in the measuring bottle of certain volume, add mobile phase and dissolve and dilute the solution becoming and be about 0.28mg/ml containing sodium sulphite, product solution in contrast.Another precision measures sodium thiosulfate inj 1ml, puts in 50ml measuring bottle, adds mobile phase and is diluted to scale, as need testing solution.
Under general condition, sulfite ion substantially without reserve, cannot separate with other ions in C18 chromatographic column.Kation is added to reagent in mobile phase, the reservation of sulfite ion in C18 chromatographic column can be increased, find after deliberation, adding 4-butyl ammonium hydrogen sulfate in mobile phase can make inferior sulfate radical have certain reservation on a column, can separate with other ions such as thiosulfate ion, but peak shape is bad, and sulfite ion poor stability in this solution; If add phosphate, and pH value is adjusted to 8.5 ~ 9.5, peak shape can be improved and sulfite ion stability in the solution can be increased, the requirement measuring sulfite content can be met.When the ratio of methyl alcohol is greater than 30%, the degree of separation of inferior sulfate radical and thiosulfate anion is bad, and the ratio of methyl alcohol lower than 10% time, analysis time extend; Methanol ratio, 10% ~ 30% time, can meet the requirement of separation, and analysis time is also reasonable.
Adopt the chromatographic condition of efficient liquid phase chromatographic analysis of the present invention, achieve the reservation of inferior sulfate radical in C18 chromatographic column, make it effectively be separated by close with its character, that the quantity of electric charge is identical thiosulfate anion, the degree of separation of sodium sulphite and sodium thiosulfate is greater than 1.5.Equally, the method is also applicable to other mensuration containing sodium sulphite product sulfite sodium content.Adopt the present invention to measure the HPLC analytical method of sodium sulphite, the retention time of sodium sulphite is about 4.5 minutes, and analysis time is short, and peak shape symmetry is good.The recovery of this method is high, and average recovery rate is 99.5%, and highly sensitive, quantitative limit reaches 3.5ng; The stability of solution reaches 8 hours.Adopt the content of method energy rapid and accurate determination sodium sulphite of the present invention.
Accompanying drawing explanation
Fig. 1 is sodium sulphite and the mixed liquid chromatogram of sodium thiosulfate, and the retention time of sodium sulphite is 4.7 minutes; The retention time of sodium thiosulfate is 5.2 minutes (adopting the chromatogram of scheme 3 gained in embodiment 1).
Fig. 2 is sodium sulphite liquid chromatogram.
Fig. 3 is the working curve diagram of sodium sulphite standard items.
Embodiment
Below by embodiment, the present invention is further illustrated, but embodiment does not limit the scope of the invention.
Key instrument and chromatographic condition:
Agilent 1200 series of high efficiency liquid chromatograph; Join VWD UV-detector, automatic sampler, Agilent chromatographic work station.
Chromatographic column: the chromatographic column taking octadecylsilane chemically bonded silica as filling agent.
Reagent and medicine:
Anhydrous sodium sulfite, sodium hydrogen phosphate, 4-butyl ammonium hydrogen sulfate, NaOH, methyl alcohol (HPLC level), sodium thiosulfate inj.
Homemade purified water is with water in experiment.
the selection of embodiment 1 chromatographic condition
The selection of 1.1 wavelength
Getting standard solution, take mobile phase as blank correction liquid, scans in 190nm ~ 400nm place according to ultraviolet-visible spectrophotometry (Chinese Pharmacopoeia version in 2010 two annex IV A).Result shows, and need testing solution has maximum absorption band at 214nm place.Therefore 214nm ± 5nm is defined as determined wavelength.
The shaker test of 1.2 methods
This test, by adjusting composition and ratio and pH value, flow velocity, the column temperature etc. of mobile phase, screens the chromatographic process of this test.Concrete scheme is in table 1.
The screening scheme of table 1 method
Precision measures sodium thiosulfate inj 1ml, puts in 25ml measuring bottle, adds mobile phase and is diluted to scale, shake up, as need testing solution.Precision measures the need testing solution of certain volume, in injection liquid chromatography, and record chromatogram.Investigate the change of sulfite ion peak and thiosulfate ion peak degree of separation.The results are shown in Table 2, scheme 3 gained chromatogram is shown in Fig. 1.
The shaker test result of table 2 method
| Scheme 1 | Scheme 2 | Scheme 3 | Scheme 4 | Scheme 5 | Scheme 6 | |
| Degree of separation | 1.52 | 1.59 | 1.85 | 1.91 | 1.93 | 1.56 |
| Symmetrical factor | 0.87 | 0.92 | 0.98 | 0.94 | 0.91 | 0.72 |
Result shows, under the chromatographic condition of scheme 1 to scheme 5, the degree of separation of sodium sulphite and sodium thiosulfate is all greater than 1.5, and the peak shape of sodium sulphite is good, and symmetrical factor, all more than 0.85, may be used for the content measuring sodium sulphite; The sodium sulphite peak shape that scheme 2 to scheme 4 obtains is better, and symmetrical factor is all greater than 0.9; Under the chromatographic condition of scheme 6, the degree of separation of sodium sulphite and sodium thiosulfate is also greater than 1.5, but the peak shape of sodium sulphite is poor, and symmetrical factor only has 0.72.
the stability of embodiment 2 solution
Take anhydrous sodium sulfite and be about 14mg, accurately weighed, put in 25ml measuring bottle, dissolve with the mobile phase in scheme 3 in embodiment 1 and be diluted to scale, shaking up, in contrast product solution one; Separately take anhydrous sodium sulfite and be about 14mg, accurately weighed, put in 25ml measuring bottle, dissolve with the mobile phase in scheme 6 in embodiment 1 and be diluted to scale, shaking up, in contrast product solution two.
Respectively measuring reference substance solution 1 μ l 0 hour, 2 hours, 4 hours, 6 hours, 8 hours precisions, test according to the chromatographic condition of scheme 3, record chromatogram.Separately, respectively measuring reference substance solution 25 μ l 0 hour, 2 hours, 4 hours, 6 hours, 8 hours precisions, test according to the chromatographic condition of scheme 6, record chromatogram.The results are shown in Table 3.
Table 3 stability of solution result
Result shows, and the result that employing scheme 6 obtains shows sodium sulfite solution poor stability with this understanding, and RSD is 7.1%.And under the condition of scheme 3 good stability of sodium sulfite solution.Illustrate that in mobile phase, add phosphate can make sodium sulfite solution stablize.
the making of embodiment 3 typical curve
Chromatographic condition: with the chromatographic condition in embodiment 1 described in scheme 3.
Take anhydrous sodium sulfite 28.1mg, 21.7mg, 14.3mg, 7.6mg, put respectively in 25ml measuring bottle, add mobile phase appropriate, after jolting makes dissolving, add mobile phase to scale, shake up, as linear solvent 1 to 4.Precision measures linear solvent 1 and each 1ml of linear solvent 3 respectively, puts respectively in 10ml measuring bottle, adds mobile phase to scale, shake up, as linear solvent 5,6.The chromatogram of linear solvent 3 is shown in Fig. 2.
Get sodium sulphite linear solvent sample introduction, with peak area and concentration mapping (see Fig. 3).In the scope of 56.0 μ g/ml ~ 1100.4 μ g/ml linearly, equation of linear regression is sodium sulfite solution:
A=3.5518C+22.0731, correlation coefficient r=0.9998.
When signal to noise ratio (S/N ratio) is 10:1, what record sodium sulphite is quantitatively limited to 3.5ng.
Result shows, under the chromatographic condition of scheme 3, linearly well, quantitative limit can meet the requirement of Accurate Determining sodium sulphite completely.
embodiment 4 recovery test
Chromatographic condition: with the chromatographic condition described in scheme in embodiment 3.
In hypo solution, add a certain amount of sodium sulphite, then measure the amount of the sodium sulphite in solution, calculate the recovery.The concentration investigated is respectively 21mg/ml, 14mg/ml, 1.4mg/ml.
The preparation of reference substance solution: precision takes anhydrous sodium sulfite 14mg, puts in 25ml measuring bottle, adds mobile phase and dissolves and be diluted to scale, shake up, to obtain final product.
Need testing solution: precision takes anhydrous sodium sulfite and is about 420mg, 280mg and adds blank hypo solution respectively and dissolve and be diluted to 20ml(concentration and be respectively 21mg/ml, 14mg/ml respectively, each concentration prepares three parts), precision measures this solution 1ml respectively, put in 50ml measuring bottle, add mobile phase to scale, shake up, to obtain final product; Another precision takes anhydrous sodium sulfite and is about 28mg and adds blank hypo solution respectively and dissolve and be diluted to 20ml(concentration and be respectively 1.4mg/ml, prepares three parts), precision measures this solution 1ml respectively, puts in 25ml measuring bottle, adds mobile phase to scale, to obtain final product;
Precision measures each 5 μ l of each solution of above-mentioned nine increment product respectively.Inject high performance liquid chromatograph, record chromatogram, by external standard method with the calculated by peak area recovery.The recovery is between 98.4% ~ 101.6%.The results are shown in Table 4.
Table 4 average recovery measurement result
Result shows, and average recovery rate is 99.5%; RSD is 1.0%, and show that the method recovery is good, accuracy is high.
embodiment 5 replica test
Chromatographic condition: with the chromatographic condition described in scheme in embodiment 3.
Precision measures sodium thiosulfate inj 1ml, puts in 25ml measuring bottle, adds mobile phase and is diluted to scale, shake up, as need testing solution.Prepare six parts.Separately get anhydrous sodium sulfite 14mg, accurately weighed, put in 25ml measuring bottle, add mobile phase appropriate, after jolting makes dissolving, add mobile phase to scale, shake up, in contrast product solution.
Get need testing solution and reference substance solution according to chromatographic condition sample introduction of the present invention, record chromatogram.By the content of external standard method calculation sample sulfite sodium.The results are shown in Table 5.
Table 5 sample repeatability testing result
| Measure number of times | 1 | 2 | 3 | 4 | 5 | 6 | RSD（%） |
| Content (mg/ml) | 13.35 | 13.28 | 13.27 | 13.34 | 13.24 | 13.24 | 0.35 |
Result represents, replica test RSD is 0.35%, is less than 2.0%, the method reproducible.
embodiment 6 sample tests
Chromatographic condition: with the chromatographic condition described in scheme in embodiment 3.
Precision measures sodium thiosulfate inj 1ml, puts in 25ml measuring bottle, adds mobile phase and is diluted to scale, shake up, as need testing solution.Separately get anhydrous sodium sulfite 14mg, accurately weighed, put in 25ml measuring bottle, add mobile phase appropriate, after jolting makes dissolving, add mobile phase to scale, shake up, in contrast product solution.
Get need testing solution and reference substance solution according to chromatographic condition sample introduction of the present invention, record chromatogram.By the content of external standard method calculation sample sulfite sodium.The results are shown in Table 6.
The measurement result of table 6 sample sulfite sodium content
| Lot number | Content (mg/ml) |
| 200911010 | 13.45 |
| 200911020 | 13.49 |
| 200911030 | 12.65 |
| 200911040 | 12.65 |
Result shows, the specificity of this method is strong, highly sensitive, precision is good, and sodium sulphite symmetry is good, can measure the content of sodium sulphite quickly and accurately.
Claims (5)
1. adopt a method for high effective liquid chromatography for measuring sodium sulphite content, it is characterized in that: take octadecylsilane chemically bonded silica as filling agent; Take methanol-water as mobile phase, wherein said aqueous phase is that its pH value is 8.5 ~ 9.5, and the volume ratio of methanol-water phase is 10:90 ~ 30:70 containing 2.0g ~ 2.5g sodium hydrogen phosphate and 0.50g ~ 1.0g 4-butyl ammonium hydrogen sulfate in 750ml aqueous phase; Determined wavelength is 214 ± 5nm; Flow velocity is 0.5ml/min ~ 1.2ml/min; Sample size is 5 μ l ~ 20 μ l.
2. the method for claim 1, is characterized in that aqueous phase is that its pH value is 9.0 containing 2.2g ~ 2.5g sodium hydrogen phosphate and 0.70g ~ 0.85g 4-butyl ammonium hydrogen sulfate in 750ml aqueous phase.
3. method as claimed in claim 1 or 2, is characterized in that the volume ratio of methyl alcohol and aqueous phase is 25:75.
4. the method for claim 1, is characterized in that flow velocity is 1.0ml/min.
5. the method for claim 1, is characterized in that column temperature is 20 DEG C ~ 30 DEG C.
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| CN106645460B (en) * | 2016-11-08 | 2019-09-17 | 同济大学 | A method of quick, Accurate Determining biogas slurry sulfite root, sulfate radical, thiosulfate anion |
| CN109100454B (en) * | 2018-10-24 | 2021-08-06 | 中国日用化学研究院有限公司 | Method for simultaneously determining content of sulfite and sulfate in surfactant product |
| CN116754691B (en) * | 2023-08-10 | 2023-11-03 | 华润双鹤利民药业（济南）有限公司 | Method for detecting impurities in paliperidone sustained release tablets by high performance liquid chromatography |
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