CN105717112A - Detection method for limit of sulfite - Google Patents

Abstract

The invention provides a detection method for the limit of sulfite. The detection method includes the following steps that 1, a sulfite standard solution is prepared; 2, the value of the drug taking amount w is obtained through calculation; 3, a test product solution is prepared; 4, a contrast solution is prepared; 5, the test product solution and the contrast solution are arranged in a first colorimetric tube and a second colorimetric tube respectively; then an excessive barium chloride solution is added to the test product solution and the contrast solution respectively, water is used for volume fixing till the volume is V4, full shaking-up is conducted, and standing is conducted for 0-120 min; whether turbidity generated by the test product solution is lower than that generated by the contrast solution or not is observed through a visual observation method; if yes, the content of sulfite in a detected drug is lower than the value of the weight limit a, and the detected drug meets the requirement. The detection method has the advantages of detecting the limit of sulfite in the drug and being easy to operate, high in sensitivity, low in needed reagent and equipment cost, safe and free of toxins and pollution.

Description

A kind of detection method of sulphite limit

Technical field

The invention belongs to sulphite detection technique field, be specifically related to the detection method of a kind of sulphite limit.

Background technology

Sulphite includes sodium sulfite, sodium sulfite, Potassium acid sulfite, Hydros, sodium pyrosulfite, potassium metabisulfite etc..In medicine preparation technology, due to commonly used sulphite as raw material or reducing agent, or; when using some degradable reagent (such as thionyl chloride); sulphite can be generated after its hydrolysis, therefore, the final medicine prepared usually can remain sulphite.

In medicine, human body is had certain hazardness by the sulphite of residual.Such as, patent CN104833639 describes with the forage feed rat containing 0.1% sodium sulfite 2 years, and rat grows and is suppressed；With the forage feed rat containing 0.1% sodium sulfite 2 years, there are the diseases such as neuritis, bone marrow suppression in rat.Open and wait quietly summing up in the toxicity and detection method summary of sulphite in foods reporting sulphite to respiratory system, reproductive system, digestive system, blood circulation, nervous system and immune impact.

Based on the understanding to sulphite toxicity, it is 0.7mg/kg that FAO and the WHO combination food additive Committee of Experts (JECFA) determines acceptable daily intake (ADI), if to be grown up, average weight calculates for 60kg, the daily ingestion of SO of human body₂Amount must not exceed 42mg, otherwise human body will be brought harm.And for medicine, different exploration projects is based on being actually needed, it will usually formulate the highest limitation of sulphite residual, thus ensureing the safety in utilization of medicine.

Therefore, in medicine preparation process, how fast and accurately whether detection medicine sulfite salt residual actual amount is below the highest limitation, significant.

In medicine detection technique field, " Chinese Pharmacopoeia " does not record the general inspection technique of sulphite limit for 2015 in version four, and the foreign pharmacopeia such as American Pharmacopeia, European Pharmacopoeia, Japanese Pharmacopoeia does not record the general inspection method of sulphite limit yet.But both at home and abroad pharmacopeia all records sulfate limit test method, method particularly includes: through the need testing solution of hcl acidifying and addition barium chloride solution in contrast solution, judge in test sample, whether the content of sulfate meets regulation by contrasting the muddy degree of two parts of solution, the method is the ripe sulfate limit test being applied to various medicine, it is a kind of general method, there is easy and simple to handle, highly sensitive, favorable reproducibility, be easy and fast to the advantages such as judgement.In domestic and international pharmacopeia, the theoretical foundation of sulfate limit test method is that barium ions can generate barium sulfate with sulfate ion in water, and barium sulfate is a kind of salt being insoluble in water, the ionic product K of its ion at normal temperatures_SPAbout 1 × 10^-10, once containing sulfate ion in solution, generate white opacity with barium ions immediately, naked eyes can be passed through and clearly distinguish, the method is easy and simple to handle, highly sensitive.

And barium sulfite slightly soluble in water, when 25 DEG C, the dissolubility in water is 0.011mg/mL, ionic product K_spIt is about 5.3 × 10^-7, and barium sulfite dissolubility is bigger in acid condition, therefore, sulfate limit test method is not particularly suited for sulphite limit test, and how fast and accurately whether detection medicine sulfite salt residual quantity meets the requirements, and is problem in the urgent need to address at present.

Summary of the invention

For the defect that prior art exists, the present invention provides the detection method of a kind of sulphite limit, can effectively solve the problems referred to above.

The technical solution used in the present invention is as follows:

An object of the present disclosure provides the detection method of a kind of sulphite limit, and the need testing solution that the detection method of this sulphite limit is used in detecting step 3 preparing is the medicine of water white transparency shape；

Comprise the following steps:

Step 1, prepares sulphite standard solution；Wherein, sulphite standard solution is with SO₂Meter concentration is c, and unit is μ g/ml；

Step 2, is calculated as follows the value obtaining the medicine amount of taking w, and unit is g:

$w=\frac{c\×b}{a}\×0.000001$

Wherein: b be the pre-designed sulphite standard solution of experiment take volume, units/ml；

A is for being detected medicine sulfite salt with SO₂The weight limit of meter, represents with %；

Step 3, prepares need testing solution:

Step 3.1, by the value of the step 2 calculated medicine amount of taking, precision weighs medicine；

Step 3.2, adds water appropriate in medicine, and shake well makes it dissolve, and as insoluble, should filter, take filtrate；

Step 3.3, it is judged that whether the solution that step 3.2 obtains is alkalescence, if it is, drip dilute hydrochloric acid to neutral in solution；Then step 3.4 is performed；Otherwise, step 3.4 is directly performed；

Step 3.4, it is V1 that solution with water step 3.3 obtained is settled to volume；Add the dilute hydrochloric acid that volume is V2 and carry out acidification, obtain acid solution；

Step 3.5, it is judged that whether the solution that step 3.4 obtains is settled solution, if it is not, then the solution that filtration step 3.4 obtains, obtains settled solution；Then step 3.6 is performed；Otherwise, step 3.6 is directly performed；

Step 3.6, it is judged that whether the settled solution that step 3.5 obtains is in water white transparency shape, if it is, perform step 3.7；

Step 3.7, drips the hydrogen peroxide of 3%～30% mass fraction in the solution that step 3.5 obtains, and the volume that hydrogen peroxide adds is V3, shake up, by adding hydrogen peroxide, being sulfate by the sulphite complete oxidation in acid solution, so far preparation obtains final need testing solution；

Step 4, prepares contrast solution:

Step 4.1, by the value of the b that step 2 adopts, precision measures the step 1 of corresponding volume and prepares the sulphite standard solution obtained；

Step 4.2, the sulphite standard solution water measured is settled to volume is V1, then, adds the dilute hydrochloric acid that volume is V2 and carries out acidification, obtain acid solution；

Step 4.3, drips the hydrogen peroxide of 3%～30% mass fraction in the acid solution that step 4.2 obtains, and the volume that hydrogen peroxide adds is V3, shakes up, and so far preparation obtains final contrast solution；

The contrast solution that step 5, need testing solution that step 3 obtains and step 4 obtain is respectively placed in No. 1 color comparison tube and No. 2 color comparison tubes；Then, in need testing solution and contrast solution, it is separately added into excessive barium chloride solution, then to be settled to volume with water respectively be V4, fully shake up, stand 0～120 minute；Ocular estimate observes the muddiness whether muddiness of need testing solution generation produces lower than contrast solution；If it is, the value that the content of detected medicine sulfite salt is lower than weight limit a, detected medicine meets the requirements；Otherwise, the content of the detected medicine sulfite salt value higher than weight limit a, detected medicine is undesirable.

Preferably, in step 1, the process for preparation of sulphite standard solution particularly as follows:

Step 1.1, precision weighs the sulphite being dissolved in water；

Step 1.2, adds purified water and dissolves sulphite, and quantitatively dilution preparation obtains the sulphite standard solution that concentration is c.

Preferably, in step 1.1, the sulphite weighed is containing inferior sulfate radical or bisulfite and the salt being dissolved in water.

Preferably, in step 1.1, the sulphite weighed is sodium sulfite, sodium sulfite, potassium sulfite or Potassium acid sulfite.

Preferably, in step 1.1, the concentration of the sulphite standard solution that preparation obtains is (with SO₂Meter) it is 10～500 μ g/ml.

Preferably, in step 2, the value of b is 1ml～10ml；

In step 3.6 and step 4.2, after addition dilute hydrochloric acid carries out acidification, obtained acid solution is substantially in acidity, and its pH value is not more than 2.0；

The barium chloride solution added in step 5 is mass fraction is the barium chloride solution of 25%, and the volume of addition is 2ml～10ml；

V1 is 30～40ml；V3 is 1ml～5ml；V4 is 50ml.

Preferably, the medicine detected is solid or solution.

The present invention the second purpose is for providing the detection method of a kind of sulphite limit, and the detection method of this sulphite limit is the coloured medicine of band for the need testing solution prepared in detecting step 3；

Comprise the following steps:

Step 1, prepares sulphite standard solution；Wherein, sulphite standard solution is with SO₂Meter concentration is c, and unit is μ g/ml；

Step 2, is calculated as follows the value obtaining the medicine amount of taking w, and unit is g:

$w=\frac{c\×b}{a}\×0.000001$

Wherein: b be the pre-designed sulphite standard solution of experiment take volume, units/ml；

A is for being detected medicine sulfite salt with SO₂The weight limit of meter, represents with %；

Step 3, prepares need testing solution A and need testing solution B:

Need testing solution A and need testing solution B all prepares in the following ways:

Step 3.1, by the value of the step 2 calculated medicine amount of taking, precision weighs medicine；

Step 3.2, adds water appropriate in medicine, and shake well makes it dissolve, and as insoluble, should filter, take filtrate；

Step 3.3, it is judged that whether the solution that step 3.2 obtains is alkalescence, if it is, drip dilute hydrochloric acid to neutral in solution；Then step 3.4 is performed；Otherwise, step 3.4 is directly performed；

Step 3.4, it is V1 that solution with water step 3.3 obtained is settled to volume；Add the dilute hydrochloric acid that volume is V2 and carry out acidification, obtain acid solution；

Step 3.5, it is judged that whether the solution that step 3.4 obtains is settled solution, if it is not, then the solution that filtration step 3.4 obtains, obtains settled solution；Then step 3.6 is performed；Otherwise, step 3.6 is directly performed；

Step 3.6, it is judged that whether the settled solution that step 3.5 obtains is with color, if it is, perform step 3.7；

Step 3.7, drips the hydrogen peroxide of 3%～30% mass fraction in the solution that step 3.5 obtains, and the volume that hydrogen peroxide adds is V3, shake up, by adding hydrogen peroxide, being sulfate by the sulphite complete oxidation in acid solution, so far preparation obtains final need testing solution；

Step 4, prepares contrast solution:

Step 4.1, adds excessive barium chloride solution in need testing solution A, fully shakes up and stand, it is judged that the whether aobvious muddiness of solution, if it is, repeatedly filter, until obtaining the filtrate of clarification；

Step 4.2, by the value of the b that step 2 adopts, precision measures the step 1 of corresponding volume and prepares the sulphite standard solution obtained；And the sulphite standard solution measured is joined in the clear filtrate that step 4.1 obtains；

Step 4.3, drips the hydrogen peroxide of 3%～30% mass fraction in the acid solution that step 4.2 obtains, and the volume that hydrogen peroxide adds is V3, shakes up, and so far preparation obtains final contrast solution；

The contrast solution that step 5, need testing solution B that step 3 obtains and step 4 obtain is respectively placed in No. 1 color comparison tube and No. 2 color comparison tubes；Then, in need testing solution B and contrast solution, it is separately added into excessive barium chloride solution, then to be settled to volume with water respectively be V4, fully shake up, stand 0～120 minute；Ocular estimate observes the muddiness whether muddiness of need testing solution generation produces lower than reference substance solution；If it is, the value that the content of detected medicine sulfite salt is lower than weight limit a, detected medicine meets the requirements；Otherwise, the content of the detected medicine sulfite salt value higher than weight limit a, detected medicine is undesirable.

The detection method of sulphite limit provided by the invention has the advantage that

(1) medicine sulfite salt limit can be detected, there is reagent simple to operate, highly sensitive, required and equipment cost is low and the free of contamination advantage of safety non-toxic.

(2) total amount of the sulphite in detection medicine and bisulfites can be merged whether beyond with SO₂The weight limit of meter.

Accompanying drawing explanation

Fig. 1 is the schematic flow sheet of the detection method of sulphite limit provided by the invention；

Fig. 2 is the process for preparation schematic flow sheet of need testing solution provided by the invention.

Detailed description of the invention

In order to make technical problem solved by the invention, technical scheme and beneficial effect clearly understand, below in conjunction with drawings and Examples, the present invention is further elaborated.Should be appreciated that specific embodiment described herein is only in order to explain the present invention, is not intended to limit the present invention.

The present invention provides the detection method of a kind of sulphite limit, and the detection method of this sulphite limit quickly can detect whether the content of medicine sulfite salt meets regulation accurately.It is emphasized that, the sulphite that the present invention relates to, unless otherwise indicated, both the salt containing inferior sulfate radical had been included, also the salt containing bisulfite is included, it is to say, the method adopting the present invention, the total amount of medicine sulfite root and bisulfite can be detected whether in limits.

Whether the detection method of sulphite limit provided by the invention, have color, and divide into two kinds of detection methods after being dissolved in water according to detected medicine, certainly, the principle of both detection methods is basically identical, below both detection methods is introduced explanation respectively:

First method: detection need testing solution is the medicine of water white transparency shape

Owing to the medicine of present invention detection can be solid, it is also possible to for liquid；Therefore, when medicine is solid, this law is applicable to the detection to solid medicine；When medicine is liquid, this law is applicable to the detection to liquid drug.

Comprise the following steps:

Step 1, prepares sulphite standard solution；Wherein, sulphite standard solution is with SO₂Meter concentration is c, and unit is μ g/ml；

In this step, the process for preparation of any standard solution in prior art can be adopted, an example is set forth below:

Step 1.1, precision weighs the sulphite being dissolved in water；

Sulphite herein is containing inferior sulfate radical or bisulfite and the salt being dissolved in water, includes but not limited to sodium sulfite, sodium sulfite, potassium sulfite or Potassium acid sulfite etc..

In this step, the concentration of the sulphite standard solution prepared can be arbitrary value, and from medicine detection angles, general concentration of standard solution is generally 1 μ g/ml, 2 μ g/ml, 5 μ g/ml, 10 μ g/ml, 50 μ g/ml, 100 μ g/ml.For the present invention, can between 10～500 μ g/ml, as a kind of optimal way, consider that sulfate ion does not include very strong with the binding ability of barium ions, binding ability lower than silver ion Yu chloride ion, therefore concentration of standard solution should be suitably larger, official requirement, usual concentration is formulated as 100 μ g/ml.

Step 1.2, adds purified water and dissolves sulphite, and quantitatively dilution preparation obtains the sulphite standard solution that concentration is c.

Step 2, is calculated as follows the value obtaining the medicine amount of taking w, and unit is g:

$w=\frac{c\×b}{a}\×0.000001$

Wherein: b be the pre-designed sulphite standard solution of experiment take volume, units/ml；

A is for being detected medicine sulfite salt with SO₂The weight limit of meter, represents with %；

0.000001: the conversion coefficient that result of calculation is converted into gram by microgram.

According to disparity items requirement, b selects different numerical value, for instance, if a project demand medicine sulfite salt content maximum is with SO₂Be calculated as 0.02%, then a value is 0.02%.

Considering sensitivity when contrasting and operability, b value lower than 1ml, should not generally also be not above 10ml.

Such as: set certain medicine sulfite salt or bisulfites (with SO₂Meter) weight limit be 0.02%, it is 5ml that the taking of established standards solution determines volume, and the concentration of sulphite standard solution is 100 μ g/ml；Then the medicine amount of taking is 2.5g

$w=\frac{100\×b}{a}\×0.000001=\frac{100\×5}{0.02\%}\×0.000001=2.5$

Step 3, prepares need testing solution:

Step 3.1, by the value of the step 2 calculated medicine amount of taking, precision weighs medicine；

Step 3.2, adds water appropriate in medicine, and shake well makes it dissolve, and as insoluble, should filter, take filtrate；

Step 3.3, it is judged that whether the solution that step 3.2 obtains is alkalescence, if it is, drip dilute hydrochloric acid to neutral in solution；Then step 3.4 is performed；Otherwise, step 3.4 is directly performed；

Step 3.4, it is V1 that solution with water step 3.3 obtained is settled to volume；Add the dilute hydrochloric acid that volume is V2 and carry out acidification, obtain acid solution；

In this step, affiliated dilute hydrochloric acid is generally the hydrochloric acid that mass fraction is 10%, and the purpose adding dilute hydrochloric acid is so that solution acidifying, and getting rid of carbonate etc. can with the barium ions interference that also this law is detected by sedimentable anion.After adding dilute hydrochloric acid, sample solution should substantially in acidity, and pH value should be not more than 2.0.

Step 3.5, it is judged that whether the solution that step 3.4 obtains is settled solution, if it is not, then the solution that filtration step 3.4 obtains, obtains settled solution；Then step 3.6 is performed；Otherwise, step 3.6 is directly performed；

Step 3.6, it is judged that whether the settled solution that step 3.5 obtains is in water white transparency shape, if it is, perform step 3.7；

Step 3.7, drips the hydrogen peroxide of 3%～30% mass fraction in the solution that step 3.5 obtains, and the volume that hydrogen peroxide adds is V3, shake up, by adding hydrogen peroxide, being sulfate by the sulphite complete oxidation in acid solution, so far preparation obtains final need testing solution；

In this step, the effect adding hydrogen peroxide is: making sulphite or bisulfites be fully oxidized generation sulfate, its chemical reaction is to be undertaken by the mol ratio of 1:1.

SO₂～SO₃ ^2-(HSO₃ ^-)～H₂O₂～SO₄ ^2-

The minimum addition k (g) of hydrogen peroxide should meet below equation:

$\frac{100(\mathrm{\μ}g/ml)\×b\left(ml\right)\×0.001}{64}=\frac{k\left(g\right)\×d\left(\%\right)\×1000}{34}$

The computing formula of k is:

$k=0.0000531\×\frac{b}{d}$

Wherein: b: add standard solution (with SO₂Meter concentration be 100 μ g/ml) volume (units/ml)

D: the mass fraction of hydrogen peroxide, represents with %

Such as: the standard solution of addition is 5ml, the mass fraction of hydrogen peroxide is 30%, then the minimum addition of hydrogen peroxide is:

$k=0.0000531\×\frac{b}{d}=0.0000531\×\frac{5}{30\%}=0.000885g$

Under room temperature, the density of hydrogen peroxide is close to 1g/ml, therefore needs 0.000885ml, namely less than 1 μ l.So, it is only necessary to add 3%～30% hydrogen peroxide 1～5ml, under any circumstance can ensure that hydrogen peroxide is significantly excessive, sulphite or bisulfites can be fully oxidized generation sulfate.

It should be noted that herein, if medicine itself does not have reproducibility, then when the standard solution of 100 μ g/ml measures and adds 1～10ml, mass fraction is that 3%～30% hydrogen peroxide adds 1～5ml, all can guarantee that hydrogen peroxide is significantly excessive, thus realizing the detection method of the present invention.But, if medicine itself has reproducibility, medicine can react with hydrogen peroxide, causes that the sulphite being detected or bisulfites can not react with hydrogen peroxide, thus the present invention cannot be realized.Therefore, detection method provided by the invention, it is only applicable to the medicine to not having reproducibility and detects.

The central principle of the present invention is that the inferior sulfate radical in medicine is completely oxidized to sulfate radical, and chemically, every strong oxidizer all can realize this requirement, such as potassium permanganate, hypochlorous acid, manganese dioxide etc.；But the present invention finally adopts visual colorimetry to judge, therefore oxidant and reduzate thereof should not be with any color, should not introduce other compositions that may interfere with yet.Owing to hydrogen peroxide is originally as colourless transparent liquid, its reduzate is water, identical with the background of this law, is also not introduced into other any compositions, therefore hydrogen peroxide is best oxidant.

Step 4, prepares contrast solution:

Step 4.1, by the value of the b that step 2 adopts, precision measures the step 1 of corresponding volume and prepares the sulphite standard solution obtained；

Step 4.2, the sulphite standard solution water measured is settled to volume is V1, then, adds the dilute hydrochloric acid that volume is V2 and carries out acidification, obtain acid solution；

Step 4.3, drips the hydrogen peroxide of 3%～30% mass fraction in the acid solution that step 4.2 obtains, and the volume that hydrogen peroxide adds is V3, shakes up, and so far preparation obtains final contrast solution；

Herein, for ensureing the comparability of follow-up contrast solution and test solution, the process for preparation adopted during preparation contrast solution to ensure consistent with the correlated process of test solution preparation as far as possible, such as, step 4.2 constant volume is as far as possible identical with the constant volume of step 3.3, and the dilute hydrochloric acid volume that step 4.2 adds is as far as possible identical with the dilute hydrochloric acid volume that step 3.3 adds.The hydrogen peroxide volume that step 4.3 adds is as far as possible identical with the hydrogen peroxide volume that step 3.7 adds.

The contrast solution that step 5, need testing solution that step 3 obtains and step 4 obtain is respectively placed in No. 1 color comparison tube and No. 2 color comparison tubes；Then, in need testing solution and contrast solution, it is separately added into excessive barium chloride solution, then to be settled to volume with water respectively be V4, fully shake up, stand 0～120 minute；Ocular estimate observes the muddiness whether muddiness of need testing solution generation produces lower than reference substance solution；If it is, the value that the content of detected medicine sulfite salt is lower than weight limit a, detected medicine meets the requirements；Otherwise, the content of the detected medicine sulfite salt value higher than weight limit a, detected medicine is undesirable.

Second method: the need testing solution prepared in detecting step 3 is for being with coloured medicine

In this method, sulphite standard solution process for preparation and need testing solution process for preparation are identical with first method.It is not described in detail in this.

Comprise the following steps:

Step 1, prepares sulphite standard solution；Wherein, sulphite standard solution is with SO₂Meter concentration is c, and unit is μ g/ml；

Step 2, is calculated as follows the value obtaining the medicine amount of taking w, and unit is g:

$w=\frac{c\×b}{a}\×0.000001$

Wherein: b be the pre-designed sulphite standard solution of experiment take volume, units/ml；

A is for being detected medicine sulfite salt with SO₂The weight limit of meter, represents with %；

Step 3, prepares need testing solution A and need testing solution B:

Need testing solution A and need testing solution B all prepares in the following ways:

Step 3.1, by the value of the step 2 calculated medicine amount of taking, precision weighs medicine；

Step 3.2, adds water appropriate in medicine, and shake well makes it dissolve, and as insoluble, should filter, take filtrate；

Step 3.3, it is judged that whether the solution that step 3.2 obtains is alkalescence, if it is, drip dilute hydrochloric acid to neutral in solution；Then step 3.4 is performed；Otherwise, step 3.4 is directly performed；

Step 3.4, it is V1 that solution with water step 3.3 obtained is settled to volume；Add the dilute hydrochloric acid that volume is V2 and carry out acidification, obtain acid solution；

Step 3.5, it is judged that whether the solution that step 3.4 obtains is settled solution, if it is not, then the solution that filtration step 3.4 obtains, obtains settled solution；Then step 3.6 is performed；Otherwise, step 3.6 is directly performed；

Step 3.6, it is judged that whether the settled solution that step 3.5 obtains is with color, if it is, perform step 3.7；

Step 3.7, drips the hydrogen peroxide of 3%～30% mass fraction in the solution that step 3.5 obtains, and the volume that hydrogen peroxide adds is V3, shake up, by adding hydrogen peroxide, being sulfate by the sulphite complete oxidation in acid solution, so far preparation obtains final need testing solution；

Step 4, prepares contrast solution:

Step 4.1, adds excessive barium chloride solution in need testing solution A, fully shakes up and stand, it is judged that the whether aobvious muddiness of solution, if it is, repeatedly filter, until obtaining the filtrate of clarification；

Step 4.2, by the value of the b that step 2 adopts, precision measures the step 1 of corresponding volume and prepares the sulphite standard solution obtained；And the sulphite standard solution measured is joined in the clear filtrate that step 4.1 obtains；

Step 4.3, drips the hydrogen peroxide of 3%～30% mass fraction in the acid solution that step 4.2 obtains, and the volume that hydrogen peroxide adds is V3, shakes up, and so far preparation obtains final contrast solution；

Herein, owing to step 3 prepares the need testing solution obtained with color, therefore, the process for preparation of the contrast solution adopted in this step is different from first method.

This step cardinal principle is:

Excessive barium chloride solution is added in need testing solution A, can by need testing solution A is likely to containing sulfate radical, inferior sulfate radical, bisulfite etc. be completely converted into precipitation, after filtering precipitation, obtain portion both without any interfering ion, the background solution that color is identical with need testing solution again.Subsequent process is namely essentially identical with first method.

The contrast solution that step 5, need testing solution B that step 3 obtains and step 4 obtain is respectively placed in No. 1 color comparison tube and No. 2 color comparison tubes；Then, in need testing solution B and contrast solution, it is separately added into excessive barium chloride solution, then to be settled to volume with water respectively be V4, fully shake up, stand 0～120 minute；Ocular estimate observes the muddiness whether muddiness of need testing solution generation produces lower than reference substance solution；If it is, the value that the content of detected medicine sulfite salt is lower than weight limit a, detected medicine meets the requirements；Otherwise, the content of the detected medicine sulfite salt value higher than weight limit a, detected medicine is undesirable.

Several embodiment is set forth below:

The inspection method of embodiment 1 ofloxacin crude drug sulfite salt limit:

(1) precision weighs anhydrous sodium sulfite 196.9mg and (is equivalent to the SO containing 100mg₂), put in 100ml measuring bottle, add purified water and dissolve and be diluted to scale, shake up；Precision measures 1ml, puts in 10ml measuring bottle, adds purified water and is diluted to scale, shakes up, as standard sodium sulfite solution (containing SO₂Concentration is 100 μ g/ml).

(2) precision weighs ofloxacin crude drug 1.0g, and add water 30ml, and shake well obtains yellow transparent solution, filtrate is put in 50ml nessler colorimetric tube, adds the dilute hydrochloric acid 2ml of 10% mass fraction, adds 30% hydrogen peroxide 2ml, shakes up, be need testing solution.A need testing solution is prepared again with method.

(3) take a need testing solution, add 30% hydrogen peroxide 2ml, add 25% barium chloride solution 5ml, stand 10 minutes, filter, take filtrate and put in 50ml nessler colorimetric tube.In filtrate, add standard sodium sulfite solution 2ml, then add 30% hydrogen peroxide 2ml, shake up, be contrast solution, be designated as A pipe.

(4) take another part of need testing solution, be designated as B pipe.

(5) in A pipe and B pipe, it is separately added into 25% barium chloride solution 5ml, is diluted with water to 50ml, fully shakes up, place 10 minutes, with putting in black background, observing down over from color comparison tube, compare, the muddiness that B pipe produces must not be richer than the muddiness (limit is 0.02%) that A pipe produces.

The inspection method of embodiment 2 Ezetimibe crude drug sulfite salt limit, comprises the following steps:

(1) precision weighs anhydrous sodium sulfite 196.9mg and (is equivalent to the SO containing 100mg₂), put in 100ml measuring bottle, add purified water and dissolve and be diluted to scale, shake up；Precision measures 1ml, puts in 10ml measuring bottle, adds purified water and is diluted to scale, shakes up, as standard sodium sulfite solution (containing SO₂Concentration is 100 μ g/ml).

(2) precision weighs Ezetimibe crude drug 1.0g, adds water appropriate, and shake well filters, filtrate put in 50ml nessler colorimetric tube, add water to 40ml, add dilute hydrochloric acid 2ml, add 20% hydrogen peroxide 3ml, shake up, be need testing solution.

(3) the quasi-sodium sulfite solution 1ml of label taking, puts in 50ml nessler colorimetric tube, adds water and makes into about 40ml, adds dilute hydrochloric acid 2ml, adds 20% hydrogen peroxide 3ml, shakes up, be contrast solution.

(4) in need testing solution and contrast solution, 25% barium chloride solution 4ml it is separately added into, it is diluted with water to 50ml, fully shake up, place 15 minutes, with putting in black background, observing down over from color comparison tube, compare, the white opacity that need testing solution produces must not richer (limit be 0.01%).

The inspection method of embodiment 3 gelatin hollow capsule shell sulfite salt limit, comprises the following steps:

(1) precision weighs anhydrous potassium sulfite 246.9mg and (is equivalent to the SO containing 100mg₂), put in 100ml measuring bottle, add purified water and dissolve and be diluted to scale, shake up；Precision measures 1ml, puts in 10ml measuring bottle, adds purified water and is diluted to scale, shakes up, as standard potassium sulfite solution (containing SO₂Concentration is 100 μ g/ml).

(2) precision weighs gelatin hollow capsule shell 2.0g, adds water appropriate, and shake well filters, filtrate put in 50ml nessler colorimetric tube, add water and make into 40ml, add dilute hydrochloric acid 2ml, add 30% hydrogen peroxide 2ml, shake up, be need testing solution.

(3) the quasi-potassium sulfite solution 2ml of label taking, puts in 50ml nessler colorimetric tube, adds water and make into about 40ml, add dilute hydrochloric acid 2ml, adds 30% hydrogen peroxide 2ml, shakes up, be contrast solution.

(4) in need testing solution and contrast solution, 25% barium chloride solution 5ml it is separately added into, it is diluted with water to 50ml, fully shake up, place 8 minutes, with putting in black background, observing down over from color comparison tube, compare, the white opacity that need testing solution produces must not richer (limit be 0.01%).

The inspection method of embodiment 4 Amino Acid Compound Injection sulfite salt limit, comprises the following steps:

(1) precision weighs sodium sulfite 162.5mg and (is equivalent to the SO containing 100mg₂), put in 100ml measuring bottle, add purified water and dissolve and be diluted to scale, shake up；Precision measures 1ml, puts in 10ml measuring bottle, adds purified water and is diluted to scale, shakes up, as standard sodium sulfite solution (containing SO₂Concentration is 100 μ g/ml).

(2) precision weighs Amino Acid Compound Injection 40.0g, puts in 50ml nessler colorimetric tube, adds dilute hydrochloric acid 2ml, adds 30% hydrogen peroxide 2ml, shakes up, be need testing solution.

(3) the quasi-sodium sulfite solution 2ml of label taking, puts in 50ml nessler colorimetric tube, adds water and makes into about 40ml, adds dilute hydrochloric acid 2ml, adds 30% hydrogen peroxide 2ml, shakes up, be contrast solution.

(4) in need testing solution and contrast solution, 25% barium chloride solution 4ml it is separately added into, it is diluted with water to 50ml, fully shake up, place 5 minutes, with putting in black background, observing down over from color comparison tube, compare, the white opacity that need testing solution produces must not richer (limit be 0.0005%).

The inspection method of embodiment 5 clarithromycin sulfite salt limit, comprises the following steps:

(1) precision weighs sodium sulfite 162.5mg and (is equivalent to the SO containing 100mg₂), put in 100ml measuring bottle, add purified water and dissolve and be diluted to scale, shake up；Precision measures 1ml, puts in 10ml measuring bottle, adds purified water and is diluted to scale, shakes up, as standard sodium sulfite solution (containing SO₂Concentration is 100 μ g/ml).

(2) taking clarithromycin appropriate, finely ground, precision weighs fine powder 5.0g, adds water appropriate, shake well, filters, filtrate is put in 50ml nessler colorimetric tube, add water and make into 40ml, add dilute hydrochloric acid 2ml, add 30% hydrogen peroxide 2ml, shake up, be need testing solution.

(3) the quasi-sodium sulfite solution 2ml of label taking, puts in 50ml nessler colorimetric tube, adds water and makes into about 40ml, adds dilute hydrochloric acid 2ml, adds 30% hydrogen peroxide 2ml, shakes up, be contrast solution.

(4) in need testing solution and contrast solution, 25% barium chloride solution 5ml it is separately added into, it is diluted with water to 50ml, fully shake up, place 10 minutes, with putting in black background, observing down over from color comparison tube, compare, the white opacity that need testing solution produces must not richer (limit be 0.004%).

The inspection method of embodiment 6 injection dexamethasone sulfite salt limit, comprises the following steps:

(1) precision weighs sodium sulfite 162.5mg and (is equivalent to the SO containing 100mg₂), put in 100ml measuring bottle, add purified water and dissolve and be diluted to scale, shake up；Precision measures 1ml, puts in 10ml measuring bottle, adds purified water and is diluted to scale, shakes up, as standard sodium sulfite solution (containing SO₂Concentration is 100 μ g/ml).

(2) precision weighs injection dexamethasone freeze-dried powder 5.0g, puts in 50ml nessler colorimetric tube, is dissolved in water and makes into 40ml, adds dilute hydrochloric acid 2ml, adds 30% hydrogen peroxide 2ml, shakes up, be need testing solution.

(3) the quasi-sodium sulfite solution 2ml of label taking, puts in 50ml nessler colorimetric tube, adds water and makes into about 40ml, adds dilute hydrochloric acid 2ml, adds 30% hydrogen peroxide 2ml, shakes up, be contrast solution.

(4) in need testing solution and contrast solution, 25% barium chloride solution 5ml it is separately added into, it is diluted with water to 50ml, fully shake up, place 10 minutes, with putting in black background, observing down over from color comparison tube, compare, the white opacity that need testing solution produces must not richer (limit be 0.004%).

The above is only the preferred embodiment of the present invention; it should be pointed out that, for those skilled in the art, under the premise without departing from the principles of the invention; can also making some improvements and modifications, these improvements and modifications also should look protection scope of the present invention.

Claims (8)

1. the detection method of a sulphite limit, it is characterised in that the need testing solution that the detection method of this sulphite limit is used in detecting step 3 preparing is the medicine of water white transparency shape；

Comprise the following steps:

Step 1, prepares sulphite standard solution；Wherein, sulphite standard solution is with SO₂Meter concentration is c, and unit is μ g/ml；

Step 2, is calculated as follows the value obtaining the medicine amount of taking w, and unit is g:

$w=\frac{c\×b}{a}\×0.000001$

Wherein: b be the pre-designed sulphite standard solution of experiment take volume, units/ml；

A is for being detected medicine sulfite salt with SO₂The weight limit of meter, represents with %；

Step 3, prepares need testing solution:

Step 3.1, by the value of the step 2 calculated medicine amount of taking, precision weighs medicine；

Step 3.2, adds water appropriate in medicine, and shake well makes it dissolve, and as insoluble, should filter, take filtrate；

Step 3.3, it is judged that whether the solution that step 3.2 obtains is alkalescence, if it is, drip dilute hydrochloric acid to neutral in solution；Then step 3.4 is performed；Otherwise, step 3.4 is directly performed；

Step 3.4, it is V1 that solution with water step 3.3 obtained is settled to volume；Add the dilute hydrochloric acid that volume is V2 and carry out acidification, obtain acid solution；

Step 3.5, it is judged that whether the solution that step 3.4 obtains is settled solution, if it is not, then the solution that filtration step 3.4 obtains, obtains settled solution；Then step 3.6 is performed；Otherwise, step 3.6 is directly performed；

Step 3.6, it is judged that whether the settled solution that step 3.5 obtains is in water white transparency shape, if it is, perform step 3.7；

Step 3.7, drips the hydrogen peroxide of 3%～30% mass fraction in the solution that step 3.5 obtains, and the volume that hydrogen peroxide adds is V3, shake up, by adding hydrogen peroxide, being sulfate by the sulphite complete oxidation in acid solution, so far preparation obtains final need testing solution；

Step 4, prepares contrast solution:

Step 4.1, by the value of the b that step 2 adopts, precision measures the step 1 of corresponding volume and prepares the sulphite standard solution obtained；

Step 4.2, the sulphite standard solution water measured is settled to volume is V1, then, adds the dilute hydrochloric acid that volume is V2 and carries out acidification, obtain acid solution；

Step 4.3, drips the hydrogen peroxide of 3%～30% mass fraction in the acid solution that step 4.2 obtains, and the volume that hydrogen peroxide adds is V3, shakes up, and so far preparation obtains final contrast solution；

The contrast solution that step 5, need testing solution that step 3 obtains and step 4 obtain is respectively placed in No. 1 color comparison tube and No. 2 color comparison tubes；Then, in need testing solution and contrast solution, it is separately added into excessive barium chloride solution, then to be settled to volume with water respectively be V4, fully shake up, stand 0～120 minute；Ocular estimate observes the muddiness whether muddiness of need testing solution generation produces lower than contrast solution；If it is, the value that the content of detected medicine sulfite salt is lower than weight limit a, detected medicine meets the requirements；Otherwise, the content of the detected medicine sulfite salt value higher than weight limit a, detected medicine is undesirable.

2. the detection method of sulphite limit according to claim 1, it is characterised in that in step 1, the process for preparation of sulphite standard solution particularly as follows:

Step 1.1, precision weighs the sulphite being dissolved in water；

Step 1.2, adds purified water and dissolves sulphite, and quantitatively dilution preparation obtains the sulphite standard solution that concentration is c.

3. the detection method of sulphite limit according to claim 2, it is characterised in that in step 1.1, the sulphite weighed is containing inferior sulfate radical or bisulfite and the salt being dissolved in water.

4. the detection method of sulphite limit according to claim 3, it is characterised in that in step 1.1, the sulphite weighed is sodium sulfite, sodium sulfite, potassium sulfite or Potassium acid sulfite.

5. the detection method of sulphite limit according to claim 1, it is characterised in that in step 1.1, the concentration of the sulphite standard solution that preparation obtains is (with SO₂Meter) it is 10～500 μ g/ml.

6. the detection method of sulphite limit according to claim 1, it is characterised in that in step 2, the value of b is 1ml～10ml；

In step 3.6 and step 4.2, after addition dilute hydrochloric acid carries out acidification, obtained acid solution is substantially in acidity, and its pH value is not more than 2.0；

The barium chloride solution added in step 5 is mass fraction is the barium chloride solution of 25%, and the volume of addition is 2ml～10ml；

V1 is 30～40ml；V3 is 1ml～5ml；V4 is 50ml.

7. the detection method of sulphite limit according to claim 1, it is characterised in that the medicine detected is solid or solution.

8. the detection method of a sulphite limit, it is characterised in that the detection method of this sulphite limit is the coloured medicine of band for the need testing solution prepared in detecting step 3；

Comprise the following steps:

Step 1, prepares sulphite standard solution；Wherein, sulphite standard solution is with SO₂Meter concentration is c, and unit is μ g/ml；

Step 2, is calculated as follows the value obtaining the medicine amount of taking w, and unit is g:

$w=\frac{c\×b}{a}\×0.000001$

Wherein: b be the pre-designed sulphite standard solution of experiment take volume, units/ml；

A is for being detected medicine sulfite salt with SO₂The weight limit of meter, represents with %；

Step 3, prepares need testing solution A and need testing solution B:

Need testing solution A and need testing solution B all prepares in the following ways:

Step 3.1, by the value of the step 2 calculated medicine amount of taking, precision weighs medicine；

Step 3.2, adds water appropriate in medicine, and shake well makes it dissolve, and as insoluble, should filter, take filtrate；

Step 3.3, it is judged that whether the solution that step 3.2 obtains is alkalescence, if it is, drip dilute hydrochloric acid to neutral in solution；Then step 3.4 is performed；Otherwise, step 3.4 is directly performed；

Step 3.4, it is V1 that solution with water step 3.3 obtained is settled to volume；Add the dilute hydrochloric acid that volume is V2 and carry out acidification, obtain acid solution；

Step 3.5, it is judged that whether the solution that step 3.4 obtains is settled solution, if it is not, then the solution that filtration step 3.4 obtains, obtains settled solution；Then step 3.6 is performed；Otherwise, step 3.6 is directly performed；

Step 3.6, it is judged that whether the settled solution that step 3.5 obtains is with color, if it is, perform step 3.7；

Step 3.7, drips the hydrogen peroxide of 3%～30% mass fraction in the solution that step 3.5 obtains, and the volume that hydrogen peroxide adds is V3, shake up, by adding hydrogen peroxide, being sulfate by the sulphite complete oxidation in acid solution, so far preparation obtains final need testing solution；

Step 4, prepares contrast solution:

Step 4.1, adds excessive barium chloride solution in need testing solution A, fully shakes up and stand, it is judged that the whether aobvious muddiness of solution, if it is, repeatedly filter, until obtaining the filtrate of clarification；

Step 4.2, by the value of the b that step 2 adopts, precision measures the step 1 of corresponding volume and prepares the sulphite standard solution obtained；And the sulphite standard solution measured is joined in the clear filtrate that step 4.1 obtains；

Step 4.3, drips the hydrogen peroxide of 3%～30% mass fraction in the acid solution that step 4.2 obtains, and the volume that hydrogen peroxide adds is V3, shakes up, and so far preparation obtains final contrast solution；

The contrast solution that step 5, need testing solution B that step 3 obtains and step 4 obtain is respectively placed in No. 1 color comparison tube and No. 2 color comparison tubes；Then, in need testing solution B and contrast solution, it is separately added into excessive barium chloride solution, then to be settled to volume with water respectively be V4, fully shake up, stand 0～120 minute；Ocular estimate observes the muddiness whether muddiness of need testing solution generation produces lower than reference substance solution；If it is, the value that the content of detected medicine sulfite salt is lower than weight limit a, detected medicine meets the requirements；Otherwise, the content of the detected medicine sulfite salt value higher than weight limit a, detected medicine is undesirable.