CN101957330B - Method for measuring content of sulfobutyl-beta-cyclodextrin - Google Patents
Method for measuring content of sulfobutyl-beta-cyclodextrin Download PDFInfo
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Abstract
The invention relates to a method for measuring content of sulfobutyl-beta-cyclodextrin, which comprises the following steps of: (1) calculating an average molecular weight through measuring an average substitution degree of the sulfobutyl-beta-cyclodextrin; (2) measuring the sulfur content of the sulfobutyl-beta-cyclodextrin by utilizing a sulfur-determining method; and (3) calculating the content of the sulfobutyl-beta-cyclodextrin by using the substitution degree and the sulfur content. The method for measuring the substitution degree of the sulfobutyl-beta-cyclodextrin in the step (1) is a nuclear magnetic resonance method; in the step (2), the sulfur content of the sulfobutyl-beta-cyclodextrin is measured by utilizing the sulfur-determining method, a sample is processed into an inorganic sulfur compound, and then, the sulfur content is measured; and different methods, such as an oxygen flask combustion method-an EDTA (Ethylene Diamine Tetraacetic Acid) titrimetric method, an Eschka reagent method-barium sulfate gravimetric method, and the like can be selected. Through the invention, the gap in the method for measuring the content of the sulfobutyl-beta-cyclodextrin in the prior art is filled, the quality control and the quality inspection are carried out on products in production, the quality of the products is improved, and the quality of the products is enhanced. The method has the advantages of less amount of the sample, high repeatability and reliable result.
Description
Technical field
The present invention relates to a kind of assay method, be specifically related to a kind of content assaying method of measuring sulphur butyl betadex by mensuration degree of substitution and element sulphur.
Background technology
Sulphur butyl betadex (sulfobutyl ether-β-cyclodextrin, SBE-β-CD) be the nineties in 20th century by the beta-cyclodextrin derivative of U.S. CyDex company exploitation, be applied to increase drug solubility and stability, improve drug bioavailability, regulate drug releasing rate, prevent the volatile ingredient loss, improve bad smell, reduce pungency, reduce aspect such as bad reaction.Sulphur butyl betadex is the product of β-CD and 1,4-butane group sultones generation substitution reaction.The most frequently used SBE-β-CD is that degree of substitution is respectively 4 and 7 SBE
4-β-CD and SBE
7-β-CD, latter's commodity are called Captisol, its sodium salt commonly used.SBE-β-CD is white or off-white color amorphous solid powder, dissolves in the 100ml water〉50g.Its relative molecular mass is: MW=1135.01+CDs * 157.99, wherein CDs is degree of substitution.Assay is a key index of sulphur butyl betadex quality control.
Beta-schardinger dextrin-is with α-1 by 7 glucopyranose residues, the 4-glycosidic bond is formed by connecting, it is up-narrow and down-wide tubular structure, and outer wall has 21 hydroxyls forms, and sulphur butyl betadex is that part of hydroxyl and the condensation of hydroxybutyl sodium sulfonate of beta-schardinger dextrin-is the product of ether.Because the complicacy of organic chemical reactions is taken SBE
7-β-CD is example, can not each beta-schardinger dextrin-be ether with the condensation of seven hydroxybutyl sodium sulfonates just, so the product of reaction is a potpourri, the degree of substitution that we obtain is an averaged result.SBE
7The degree of substitution scope dictates of the product of-β-CD commodity Captisol by name is 6.0～7.1.
The mensuration of sulphur butyl betadex degree of substitution has nuclear-magnetism method, mass spectroscopy, elemental microanalysis method etc.(Song Aijing, Wang Jianhua, Liu Chundong, etc. single stage method is synthesized medicinal biological material sulfoalkyl ether-beta-cyclic dextrine derivant. Science Bulletin, 2009,54:1362 ~ 1373).
Mass spectroscopy and elemental microanalysis method are because the restriction of instrument etc., and resultant error is bigger.
The method of the assay of sulphur butyl betadex is not seen the domestic and foreign literature report.
At present in the organic compound commonly used the assay method majority of sulphur be with sulphur in the sample by being processed into the sulfur-bearing mineral compound under the aerobic hot conditions, measure the content of inorganic total sulfur again by different detection meanss, calculate organic sulfur content.
Horse has been cooked toward school etc. and has decided the research that the sulphur method is measured allicin content and influence factor in the garlic, and allicin is oxidized to sulfate ion, forms barium sulfate precipitate with the barium chloride reaction, weighs, and is converted into the content of allicin.
The advantage of the method be easy, quick, reagent consumption is few.It is more that but shortcoming is influence factor, as the consumption of oxygenant; (the pH value is little, causes sour effect, and the precipitation solubleness of generation increases for acidity (between pH2 ~ 3), make the result on the low side, when the pH value increased, the acidity of solution was less, the cation easily generation hydrolysis of weak base salt has reduced cation concn, thereby also causes measurement result on the low side; Precipitation agent consumption (barium chloride consumption) consumption is very few, then makes precipitation not exclusively, and the result is on the low side.
According to common-ion effcet, excessive precipitator helps precipitation fully, then can produce salt effect but the precipitation agent consumption is excessive, and the solubleness of precipitation is increased, and makes the result on the low side.Make the result on the low side easily.(content assaying method of sulfurous organic compound: decide the sulphur method and measure allicin content and influence factor in the garlic, " research and development of natural products ", 2002 the 14th the 6th phases of volume)
PSS standard (two ones the 4th of E4-120 standard numbering nineteen ninety-five the Sanitation Ministry medicine standard) provides an oxygen bottle burning, and the method for alginate diester sodium content method is measured in EDTA complexometry:
Get the about 0.1g of sample, the accurate title, decide, and carries out organic destruction according to oxygen flask combustion method (38 pages of two appendix of Chinese Pharmacopoeia nineteen ninety version), uses the 500ml Molotov cocktail, is absorption liquid with superoxol (30%) 0.5ml, water 20ml.After smog to be generated sucks absorption liquid fully, add hydrochloric acid (1mol/L) 2ml, put to be heated to closely in the water-bath and boil.Accurate barium chloride liquid (0.05mol/L) 15ml that drips, continued to boil 5 minutes, put cold, add bromothymol blue indicator solution number droplet, be neutralized to apparent blueness with caustic lye of soda (2mol/L), ammonification-ammonium chloride buffer (pH10) 10ml, precision adds magnesium chloride liquid (0.05mol/L) 15ml, chromium black T indicator is an amount of,, and titration results proofreaied and correct with blank test to pure blue with Calcium Disodium Versenate liquid (0.05mol/L) titration.Every 1ml Calcium Disodium Versenate liquid (0.05mol/L) is equivalent to the S of 1.603mg.
Su Wei etc. study the sulphur that EDTA complexometry is measured in the heavy oil, think influence the factor of titration accuracy can be summed up as following some:
(1) ammonia-ammonium chloride buffer is long standing time, and damping fluid lost efficacy, and titration end-point changes and causes error in judgement, and for avoiding this type of error, damping fluid will be looked for novelty and be joined.
(2) contain micro-metallic element in the heavy oil, the coordination ability of EDTA and metallic ion is very strong, thereby influences titration results.
(3) preparation of barium chloride, magnesium chloride standard solution also has certain influence to titration results.
(4) operator also can cause different experimental biases to the visual sensitivity of titration end-point color.
Although above some final result is had either large or small influence, they all also do not cause great influence to accuracy and the precision of titrimetry.(sulphur in the heavy oil is measured in EDTA complexometry, " Hubei Electric Power ", the 24th the 1st phase of volume of March in 2000)
Pang Xiuyan etc. provide an Emhorn cassette agent to digest the method that barium sulfate turbidimetry is measured the sulfur content in the expanded graphite, after adopting the agent of an amount of Emhorn cassette that the sulphur in the graphite is all changed into the form of sulfate, in conjunction with measuring with the barium sulfate turbidimetry under the acid condition, measure sulfur content again.(Emhorn cassette agent digestion barium sulfate turbidimetry is measured the sulfur content in the expanded graphite, University Of Hebei's journal (natural science edition) the 28th volume first phase of January in 2008).
Zou Yunxiang etc. provide sulphur in a kind of ion-chromatographic determination oil sample and the tar benzene and the method for chlorine, earlier sample combustion are processed into inorganic ions, then by the ion chromatography sulfate radical, measure the content of sulphur.(sulphur and chlorine in ion-chromatographic determination oil sample and the tar benzene, Liaoning chemical industry, 59～60 pages of the 5th phases of nineteen ninety-five).
Summary of the invention
The purpose of this invention is to provide a kind of sulphur butyl betadex Determination on content method, this method adopts the average substitution degree of mensuration sulphur butyl betadex and the quality of total sulfur, the content that content and degree of substitution by sulphur calculates sulphur butyl betadex solves the assay problem of sulphur butyl betadex with this.To fill up the blank of the content assaying method of sulphur butyl betadex in the prior art, and and then the product in producing carried out quality control and check, thereby improve the quality of product, improve the quality of product, and this method has, and amount of samples is few, reappearance is high, the advantage of reliable results.
Technical scheme of the present invention is: a kind of sulphur butyl betadex Determination on content method is characterized in that step is as follows:
⑴ by measuring sulphur butyl betadex average substitution degree;
⑵ adopt the sulfur content of deciding in the sulphur method mensuration sulphur butyl betadex;
⑶ calculate the content of sulphur butyl betadex with the content of degree of substitution and sulphur.
Sulphur butyl betadex is the organic compound of sulfur-bearing and since its in ultraviolet the short wavelength, and reference substance can't obtain, chromatogram analysis method therefore commonly used all can not satisfy the assay requirement.The present invention considers that it is sulfocompound, the therefore average substitution degree by working sample, thereby the mean molecular weight of calculation sample, and the percentage composition of working sample sulphur again calculates the content of sulphur butyl betadex by mean molecular weight and sulfur content.
More particularly, the concrete operations of each step of the present invention are:
⑴ the calculating of mensuration, calculating and the mean molecular weight of nuclear magnetic resonance method sulphur butyl betadex degree of substitution:
Proton on seven H1(anomeric carbons of beta-schardinger dextrin-in the sulphur butyl betadex in nuclear magnetic resonance method) chemical shift is greatly about 4.8～5.1ppm, and its integral area is A
1, the 2-position of sulphur butyl is identical with 3-position methylenation displacement study, and about 1.63ppm, its integral area is A
2, can calculate its degree of substitution according to the two integral area, computing formula is as follows: degree of substitution DS=7A
2/ 4A
1The computing formula of molecular weight: M=1135+158DS
⑵ adopt the sulfur content of deciding in the sulphur method mensuration sulphur butyl betadex;
The operation of step ⑵ can have following different selection:
A oxygen flask combustion method-EDTA titrimetry: the sulphur butyl betadex of certain mass is placed the Molotov cocktail that is full of oxygen, under the catalytic action of platinum filament, burn, make sulphur butyl betadex be decomposed into inorganic ions type sulfocompound fast, and the superoxol of usefulness absorption products of combustion, get sulfur acid root absorption liquid;
It is an amount of that absorption liquid adds hydrochloric acid, put to be heated to closely in the water-bath and boil, the accurate barium chloride liquid that drips, continue to boil, put cold, add bromothymol blue indicator solution number droplet, be neutralized to apparent blue with caustic lye of soda, ammonia-the ammonium chloride buffer that adds pH10, precision adds magnesium chloride liquid (0.05mol/L), chromium black T indicator is an amount of, uses Calcium Disodium Versenate liquid (0.05mol/L) titration to pure blue, and titration results is proofreaied and correct with blank test, by used up EDTA amount, calculate the sulfur content in the sulphur butyl betadex;
Principle:
Sulphur fourth+O
2→ Na
2SO
4+ CO
2↑+SO
3↑
SO
3+?H
2O→H
2SO
4
SO
4 2-?+Ba
2+?→BaSO
4↓
Before the titration: Ba
2++ HIn
2-→ Baln
-+ H
+
Mg
2++ HIn
2-→ MgIn
-+ H
+Solution takes on a red color
After the titration: Baln
-+ H
2Y
2-→ BaY
2-+ HIn
2-+ H
+
MgIn
-+ H2Y
2-→ MgY
2-+ HIn
2-+ H
+Solution is pure blue
HIn wherein
2-Be eriochrome black T metallic ion indicator, H
2Y
2-Be EDTA solution
According to reaction principle, by blank correction, the EDTA solution that every consumption is one mole just consumes one mole sulphur accordingly, therefore according to the concentration 0.05mol/L of sulphur relative molecular weight 32.07 and EDTA, calculates:
Every 1ml Calcium Disodium Versenate liquid (0.05mol/L) is equivalent to the S of 1.603mg, and its concrete formula is: (0.05 mol/L) * (0.00 l L) * (* (1000mg/g)=1.603mg of 32.07g/mol);
B Emhorn card reagent method-barium sulphate gravimetric method: sulphur butyl betadex and the Emhorn card reagent mix of certain mass are evenly also at high temperature carried out the fritting reaction, with half molten reacted clinker, use water extraction, make sulphur butyl betadex be converted into water-soluble sulfate, filter, i.e. sulfur-bearing acid group aqueous solution;
Metabisulfite solution with hydrochloric acid adjust pH 1 ~ 2, is added barium chloride solution, filter, will be deposited in 850 ℃ of calcinations to constant weight, weigh, do blank test simultaneously and proofread and correct, calculate the sulfur content in the sulphur butyl betadex;
Principle:
Sulphur fourth+air+Na
2CO
3→ CO2 ↑+H
2O+Na
2SO
4
The MgO reactant that can loosen makes air can enter sample in the Emhorn card reagent, also can react by sulphur butyl betadex simultaneously:
Sulphur fourth+air+MgO → MgSO
4+ CO2 ↑+H
2O+ Na
2SO
4
The transformation of sulfate:
MgSO
4+?Na
2CO
3→Na
2SO
4+MgCO
3↓
Therefore the sulphur in the sulphur fourth all is converted into water-soluble Na after the fritting reaction
2SO
4, filter, regulate filtrate acidity, make it be acid (pH1 ~ 2), purpose is to eliminate excessive N a
2CO
3Influence, because of its also can and Ba
2+In neutral solution, form BaCO
3Precipitation adds Ba
2+The back generates barium sulfate precipitate:
Ba
2++SO
4 2-→BaSO
4↓
Leach BaSO
4Precipitation is through washing, oven dry, ashing, calcination, weigh.Measurement result is calculated as follows:
The quality of sulphur=(m
1-m
2) * 0.1374
In the formula: m
1Be BaSO after the calcination
4Quality; m
2BaSO for blank test
4Quality; 0.1374 by BaSO
4Be converted into the quality of sulphur.
C oxygen flask combustion method-barium sulphate gravimetric method: with the content of sulfur-bearing acid group aqueous solution in the scheme 2 with barium sulphate gravimetric determination sulphur in the scheme 3, calculate the sulfur content in the sulphur butyl betadex;
D Emhorn card reagent method-EDTA titrimetry: with the content of metabisulfite solution in the scheme 3 with EDTA titration measuring sulphur in the scheme 2, calculate the sulfur content in the sulphur butyl betadex;
E oxygen flask combustion method or Emhorn card reagent method-barium chromate spectrophotometric method: resulting sulfate liquor in scheme 2 or the scheme 3 is transferred to pH1 ~ 2 with hydrochloric acid, make sulfate and barium chromate generate barium sulfate precipitate and chromate ion, with ammonia spirit with in the solution and after, the barium chromate that elimination is unnecessary and barium sulfate precipitate, the chromate solution of colorimetric estimation yellow under wavelength 420nm or 440nm, according to 5mg/L ~ 200mg/L sulfate radical with the typical curve of drawing under the equiwavelength, obtain the content of sulfate, calculate the sulfur content in the sulphur butyl betadex;
Principle: 2BaCrO
4+ 4H
+→ H
2Cr
2O
7+ 2Ba
++ H
2O
Ba
++?SO
4 2-→BaSO
4↓
The unnecessary BaCrO of filtering
4And BaSO
4Precipitation
H
2Cr
2O
7+ H
2O → 2H
2CrO
4Wavelength 420nm or 440nm colorimetric
Typical curve: y=b*x+a wherein y is absorbance, and x is SO
4 2-Content (mg), convert SO
4 2-Be concentration (mg/L):
x=（y-a）/b
SO
4 2-In sulfur content be: 32/96* x=0.3333*(y-a)/b
f
Oxygen flask combustion method or Emhorn card reagent method-barium sulfate turbidimetry: with resulting sulfate liquor in scheme 2 or the scheme 3, the adding barium chloride precipitates sulfate radical fully and generates trickle barium sulphate crystallization and forms uniform suspension, colorimetric estimation absorbance under wavelength 420nm, be directly proportional with sulphates content and the quantity relative ratio relationship of known series concentration barium sulfate suspension and absorbance by its muddy degree, the content of sulphur calculates the sulfur content in the sulphur butyl betadex as can be known;
G oxygen flask combustion method or Emhorn card reagent method-chromatography of ions refer to: with resulting sulfate liquor in scheme 2 or the scheme 3, enter ion exchange system with leacheate, separate according to the different affinity of separating column to various negative ion, with peak height or peak area quantification, measure the concentration of sulfate radical, calculate the sulfur content in the sulphur butyl betadex;
⑶ calculate the content of sulphur butyl betadex with the content of degree of substitution and sulphur.
The molecular structure of the sulphur butyl betadex in of the present invention and concrete degree of substitution are known, and its molecular formula is C
42H
70-xO
35(C
4H
8SO
3Na)
xTherefore can extrapolate the content of sulphur butyl betadex by the quality of molecular weight and degree of substitution and the sulphur that records, specific as follows:
Sulphur butyl betadex cubage formula: sulphur fourth %=m
s/ 32* DS/(1135+158*DS) }/m * 100%
Wherein: m
sFor testing the quality of the sulphur of surveying, mg
DS is the degree of substitution of sulphur butyl betadex
M is weighing sulphur butyl betadex (quality behind the deduction moisture content), mg
Technological merit of the present invention: the content assaying method that a kind of sulphur butyl betadex is provided, solved the assay problem of sulphur butyl betadex with this, and then can carry out quality control and check to the product in producing, thereby improve the quality of product, improved the quality of product, and this method has, and amount of samples is few, reappearance is high, the advantage of reliable results.
Description of drawings
Fig. 1 is the mensuration collection of illustrative plates of sulphur butyl betadex degree of substitution among the embodiment 1.
Embodiment
Discuss in detail below in conjunction with the present invention of embodiment.
Embodiment 1, the degree of substitution of nmr for the determination sulphur butyl betadex
Measuring unit: Institute of Analysis of China Medicine University
Instrument: BRUKER AV-500 type nuclear magnetic resonance analyser
Solvent: D2O
Interior mark: TSP
Temperature: 303K
Measure collection of illustrative plates and see accompanying drawing 1, degree of substitution is 24.642/4=6.16
Embodiment 2, oxygen flask combustion method-EDTA titrimetry
Get sulphur butyl betadex 100mg, the accurate title, decide, carrying out organic destruction according to oxygen flask combustion method (two appendix VII of Chinese Pharmacopoeia version in 2005 C oxygen flask combustion method), use the 500ml Molotov cocktail, is absorption liquid with superoxol (30%) 0.5ml, water 20ml, static 15min, make the smog of generation suck absorption liquid fully, open bottle stopper, with low amounts of water flushing bottle stopper and platinum filament load sampler, merge washing lotion and absorption liquid, namely get sulfate solution;
Absorption liquid adds hydrochloric acid (1mol/L) 2ml, puts to be heated to closely in the water-bath and boils; Accurate barium chloride liquid (0.05mol/L) 15ml that drips, continued to boil 5 minutes, put cold, add bromothymol blue indicator solution number droplet, be neutralized to apparent blue with caustic lye of soda (2mol/L), ammonification-ammonium chloride buffer (pH10) 10ml, precision adds magnesium chloride liquid (0.05mol/L) 15ml, chromium black T indicator makes solution be aubergine in right amount, with Calcium Disodium Versenate liquid (Na
2H
2Y2H
2O, EDTA solution) (0.05mol/L) titration and is proofreaied and correct titration results to pure blue with blank test.Calculate sulfur content, calculate sulphur butyl betadex content according to degree of substitution and sulfur content, the result is 100.4%.
Embodiment 3, Emhorn card reagent method-barium sulphate gravimetric method
Sulphur butyl betadex and 2g Emhorn card reagent (2MgONa with 100mg
2CO
3) place the porcelain crucible of 30ml, mix, cover 1g Emhorn card reagent above again, and crucible placed muffle furnace, in 2h, be raised to 850 ℃ from room temperature, and insulation 2h, the taking-up crucible is put and is chilled to room temperature, smashs clinker to pieces and places the 500ml beaker, with the flushing of 100 ~ 150ml hot distilled water and stirring clinker, make fragmentary, boil 5min, leach insolubles with qualitative filter paper, qualitative filter paper leaches insolubles and collects filtrate, continue with hot distilled water purge insolubles repeatedly to make final filtrate volume be no more than 300ml;
Drip methyl orange (2g/L) indicator number droplet in the filtrate, with hydrochloric acid adjust pH 1 ~ 2, and be heated to little boiling, drip 10ml barium chloride solution (100g/L) while stirring, insulation 2h filters with quantitative filter paper at a slow speed, and being washed till filtrate with hot distilled water does not have Cl
-, will be deposited in 850 ℃ of calcinations to constant weight, weigh, do blank test simultaneously and proofread and correct, calculate sulfur content, calculate sulphur butyl betadex content according to degree of substitution and sulfur content.
Embodiment 4, oxygen flask combustion method-barium sulphate gravimetric method
The aqueous solution method for making of sulfate is with embodiment 2, and difference is that what to measure that the method for sulphates content adopts is barium sulphate gravimetric method among the embodiment 3, calculates the content of sulphur butyl betadex, and content results is 98.5%.
Embodiment 5, Emhorn card reagent method-EDTA titrimetry
The aqueous solution method for making of sulfate is with embodiment 3, and difference is that what to measure that the method for sulphates content adopts is EDTA titrimetry among the embodiment 2, calculates the content of sulphur butyl betadex, and content results is 101.3%.
Embodiment 6: oxygen flask combustion method-barium chromate spectrophotometric method
Sulfate standard solution preparation: take by weighing the 1.4786g anhydrous sodium sulfate or anhydrous potassium sulfate 1.8141g is soluble in water, and fixed molten to 1000ml, get the sulfate liquor (SO that 1ml contains 1mg
4 2-).
The preparation of barium chromate hydrochloric acid solution: take by weighing barium chromate 25g, be dissolved in the hydrochloric acid of 2.5mol/L, fixed molten to 1000ml.
The drafting of sulfate radical typical curve: in 10 50 ml color comparison tubes, add 0.00,0.25,0.50,1 respectively.00,2.00,3.00,4.00,6.00,8.00,10.00ml sulfate standard solution, add water to about 25 ml, respectively add 2.5 ml barium chromate hydrochloric acid solutions, 70 ℃ of water-bath 5 min, transfer to scale (50ml) with 1+1 ammoniacal liquor again, shake up, filter with middling speed filter paper, discard about 5 ml of initial filtrate, collect yellow filtrate in 25 ml color comparison tubes of drying, under 420 nm wavelength, use the 0.5cm cuvette with spectrophotometer, make reference with pure water, measure absorbance, being able to absorbance is ordinate (y), and the sulphates content in each pipe (mg) is made horizontal ordinate (x) and set up regression equation y=b*x+a, gets typical curve: y=0.02493*x-0.0011.
With resulting sulfate liquor among the embodiment 2, make sulfate and barium chromate generate barium sulfate precipitate and chromate ion, with ammonia spirit with in the solution and after, the barium chromate that elimination is unnecessary and barium sulfate precipitate, the chromate solution of colorimetric estimation yellow under 420nm, with the typical curve of drawing under the equiwavelength, obtain the content of sulfate according to 5mg/L ~ 200mg/L sulfate radical, calculate the content of sulphur butyl betadex.
Embodiment 7, and with embodiment 2, the used wavelength of difference is colorimetric under the 440nm.
Embodiment 8, Emhorn card reagent method-barium chromate spectrophotometric method
Resulting sulfate liquor among the embodiment 3 is transferred to pH1 ~ 2 with hydrochloric acid, make sulfate and barium chromate generate barium sulfate precipitate and chromate ion, with ammonia spirit with in the solution and after, the barium chromate that elimination is unnecessary and barium sulfate precipitate, the chromate solution of colorimetric estimation yellow under 420nm, with the typical curve of drawing under the equiwavelength, obtain the content of sulfate according to 5mg/L ~ 200mg/L sulfate radical, calculate the content of sulphur butyl betadex.
Embodiment 9, and with embodiment 8, the used wavelength of difference is colorimetric under the 440nm.
Embodiment 10, oxygen flask combustion method-barium sulfate turbidimetry:
With resulting sulfate liquor in scheme 2 or the scheme 3, the adding barium chloride precipitates sulfate radical fully and generates trickle barium sulphate crystallization and forms uniform suspension, colorimetric estimation absorbance under 420nm, be directly proportional with sulphates content and the quantity relative ratio relationship of known series concentration barium sulfate suspension and absorbance by its muddy degree, the content of sulphur as can be known calculates the content of sulphur butyl betadex.
Embodiment 11, Emhorn card reagent method-barium sulfate turbidimetry:
With resulting sulfate liquor in scheme 2 or the scheme 3, the adding barium chloride precipitates sulfate radical fully and generates trickle barium sulphate crystallization and forms uniform suspension, colorimetric estimation absorbance under 420nm, be directly proportional with sulphates content and the quantity relative ratio relationship of known series concentration barium sulfate suspension and absorbance by its muddy degree, the content of sulphur as can be known calculates the content of sulphur butyl betadex.
Embodiment 12, oxygen flask combustion method-chromatography of ions:
With resulting sulfate liquor in scheme 2 or the scheme 3, enter ion exchange system with leacheate, separate according to the different affinity of separating column to various negative ion, with peak height or peak area quantification, measure the concentration of sulfate radical, calculate the content of sulphur butyl betadex.
Embodiment 13, Emhorn card reagent method-chromatography of ions:
With resulting sulfate liquor in scheme 2 or the scheme 3, enter ion exchange system with leacheate, separate according to the different affinity of separating column to various negative ion, with peak height or peak area quantification, measure the concentration of sulfate radical, calculate the content of sulphur butyl betadex.
More than the description of preferred embodiments of the present invention is not limited the present invention, those skilled in the art can make various changes or distortion according to the present invention, only otherwise break away from spirit of the present invention, all should belong to the scope of claims of the present invention.
Claims (4)
1. the content assaying method of a sulphur butyl betadex is characterized in that step is as follows:
⑴ calculate mean molecular weight by measuring sulphur butyl betadex average substitution degree;
⑵ adopt the sulfur content of deciding in the sulphur method mensuration sulphur butyl betadex;
⑶ calculate the content of sulphur butyl betadex with the content of degree of substitution and sulphur;
Wherein the degree of substitution assay method of the described sulphur butyl of step ⑴ betadex is nuclear magnetic resonance method, and its concrete operations are:
The calculating of mensuration, calculating and the mean molecular weight of nuclear magnetic resonance method sulphur butyl betadex degree of substitution:
In the sulphur butyl betadex, proton on seven anomeric carbons of beta-schardinger dextrin----the chemical shift of H1 is at 4.8～5.1ppm in nuclear magnetic resonance method, and its integral area is A
1, the 2-position of sulphur butyl is identical with 3-position methylenation displacement study, and about 1.63ppm, its integral area is A
2, can calculate its degree of substitution according to the two integral area, computing formula is as follows: degree of substitution DS=7A
2/ 4A
1The computing formula of molecular weight: M=1135+158DS;
Sulphur butyl betadex cubage formula: sulphur fourth %=m
s/ 32* DS/(1135+158*DS) }/m * 100%
Wherein: m
sFor testing the quality of the sulphur of surveying, mg
DS is the degree of substitution of sulphur butyl betadex
M is the quality behind the weighing sulphur butyl betadex deduction moisture content, mg.
2. the content assaying method of sulphur butyl betadex according to claim 1, it is characterized in that, wherein the sulfur content in the sulphur method mensuration sulphur butyl betadex is decided in the described employing of step ⑵, is that sample is processed into inorganic sulfocompound under certain condition, measures the content of sulphur again.
3. the content assaying method of sulphur butyl betadex according to claim 1 is characterized in that, wherein the described employing of step ⑵ is decided the sulphur method and measured sulfur content in the sulphur butyl betadex, is to select a kind of in the following method:
A oxygen flask combustion method-EDTA titrimetry;
B Emhorn card reagent method-barium sulphate gravimetric method;
C oxygen flask combustion method-barium sulphate gravimetric method;
D Emhorn card reagent method-EDTA titrimetry;
E oxygen flask combustion method or Emhorn card reagent method-barium chromate spectrophotometric method;
f
Oxygen flask combustion method or Emhorn card reagent method-barium sulfate turbidimetry;
G oxygen flask combustion method or Emhorn card reagent method-chromatography of ions.
4. the content assaying method of sulphur butyl betadex according to claim 3 is characterized in that, the concrete operations that the sulfur content in the sulphur method mensuration sulphur butyl betadex is decided in the described employing of step ⑵ are respectively:
A oxygen flask combustion method-EDTA titrimetry: the sulphur butyl betadex of certain mass is placed the Molotov cocktail that is full of oxygen, under the catalytic action of platinum filament, burn, make sulphur butyl betadex be decomposed into inorganic ions type sulfocompound fast, and absorb products of combustion with superoxol, get sulfur acid root absorption liquid;
It is an amount of that absorption liquid adds hydrochloric acid, put to be heated to closely in the water-bath and boil, the accurate barium chloride liquid that drips, continue to boil, put cold, add bromothymol blue indicator solution number droplet, be neutralized to apparent blue with caustic lye of soda, adding pH is ammonia-ammonium chloride buffer of 10, precision adds magnesium chloride liquid, chromium black T indicator is an amount of, and is fixed to pure blue with the Calcium Disodium Versenate drop, and titration results is proofreaied and correct with blank test, by used up EDTA amount, calculate the sulfur content of sulphur butyl betadex and the content that calculates sulphur butyl betadex with the content of degree of substitution and sulphur;
B Emhorn card reagent method-barium sulphate gravimetric method: sulphur butyl betadex and the Emhorn card reagent mix of certain mass are evenly also at high temperature carried out the fritting reaction, with the reacted clinker of fritting, use water extraction, make sulphur butyl betadex be converted into water-soluble sulfate, filter, i.e. sulfur-bearing acid group aqueous solution;
Metabisulfite solution with hydrochloric acid adjust pH 1 ~ 2, is added barium chloride solution, filter, to be deposited in 850 ℃ of calcinations to constant weight, weigh, do blank test simultaneously and proofread and correct, calculate the sulfur content of sulphur butyl betadex and the content that calculates sulphur butyl betadex with the content of degree of substitution and sulphur;
C oxygen flask combustion method-barium sulphate gravimetric method: with the content of the sulfur-bearing acid group aqueous solution in described a oxygen flask combustion method-EDTA titrimetry with barium sulphate gravimetric determination sulphur in described b Emhorn card reagent method-barium sulphate gravimetric method, calculate the sulfur content of sulphur butyl betadex and the content that calculates sulphur butyl betadex with the content of degree of substitution and sulphur;
D Emhorn card reagent method-EDTA titrimetry: with the content of metabisulfite solution in described b Emhorn card reagent method-barium sulphate gravimetric method with the oxygen flask combustion method-EDTA titration measuring sulphur in the scheme 2, calculate the sulfur content of sulphur butyl betadex and the content that calculates sulphur butyl betadex with the content of degree of substitution and sulphur;
E oxygen flask combustion method or Emhorn card reagent method-barium chromate spectrophotometric method: resulting sulfate liquor in described a oxygen flask combustion method-EDTA titrimetry or the described b Emhorn card reagent method-barium sulphate gravimetric method is transferred to pH1 ~ 2 with hydrochloric acid, make sulfate and barium chromate generate barium sulfate precipitate and chromate ion, with ammonia spirit with in the solution and after, the barium chromate that elimination is unnecessary and barium sulfate precipitate, the chromate solution of colorimetric estimation yellow under wavelength 420nm or 440nm, according to 5mg/L ~ 200mg/L sulfate radical with the typical curve of drawing under the equiwavelength, obtain the content of sulfate, calculate the sulfur content of sulphur butyl betadex and the content that calculates sulphur butyl betadex with the content of degree of substitution and sulphur;
f
Oxygen flask combustion method or Emhorn card reagent method-barium sulfate turbidimetry are with resulting sulfate liquor in described a oxygen flask combustion method-EDTA titrimetry or the described b Emhorn card reagent method-barium sulphate gravimetric method, the adding barium chloride precipitates sulfate radical fully and generates trickle barium sulphate crystallization and forms uniform suspension, colorimetric estimation absorbance under wavelength 420nm, be directly proportional with sulphates content and the quantity relative ratio relationship of known series concentration barium sulfate suspension and absorbance by its muddy degree, the content of sulphur calculates the sulfur content of sulphur butyl betadex and the content that calculates sulphur butyl betadex with the content of degree of substitution and sulphur as can be known;
G oxygen flask combustion method or Emhorn card reagent method-chromatography of ions: resulting sulfate liquor in described a oxygen flask combustion method-EDTA titrimetry or the described b Emhorn card reagent method-barium sulphate gravimetric method, enter ion exchange system with leacheate, separate according to the different affinity of separating column to various negative ion, with peak height or peak area quantification, measure the concentration of sulfate radical, calculate the sulfur content of sulphur butyl betadex and the content that calculates sulphur butyl betadex with the content of degree of substitution and sulphur.
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| CN104458879A (en) * | 2014-09-26 | 2015-03-25 | 浙江工商大学 | Concentration detection device and method for beta-cyclodextrin solution |
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