CN102565046A - Method for rapidly detecting mifepristone - Google Patents
Method for rapidly detecting mifepristone Download PDFInfo
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- CN102565046A CN102565046A CN2011104492764A CN201110449276A CN102565046A CN 102565046 A CN102565046 A CN 102565046A CN 2011104492764 A CN2011104492764 A CN 2011104492764A CN 201110449276 A CN201110449276 A CN 201110449276A CN 102565046 A CN102565046 A CN 102565046A
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- mifepristone
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- sulfuric acid
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- 229960003248 mifepristone Drugs 0.000 title claims abstract description 110
- VKHAHZOOUSRJNA-GCNJZUOMSA-N mifepristone Chemical compound C1([C@@H]2C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]3CC[C@@]([C@]3(C2)C)(O)C#CC)=CC=C(N(C)C)C=C1 VKHAHZOOUSRJNA-GCNJZUOMSA-N 0.000 title claims abstract description 110
- 238000000034 method Methods 0.000 title claims abstract description 88
- 239000003814 drug Substances 0.000 claims abstract description 78
- 239000002904 solvent Substances 0.000 claims abstract description 77
- 239000000284 extract Substances 0.000 claims abstract description 29
- 230000008859 change Effects 0.000 claims abstract description 28
- HZWXJJCSDBQVLF-UHFFFAOYSA-N acetoxysulfonic acid Chemical compound CC(=O)OS(O)(=O)=O HZWXJJCSDBQVLF-UHFFFAOYSA-N 0.000 claims abstract description 25
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 25
- 238000000605 extraction Methods 0.000 claims abstract description 15
- 239000000203 mixture Substances 0.000 claims abstract description 11
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic anhydride Substances CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 58
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 44
- 238000002360 preparation method Methods 0.000 claims description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 18
- 238000001514 detection method Methods 0.000 claims description 17
- 239000003960 organic solvent Substances 0.000 claims description 9
- 238000007689 inspection Methods 0.000 claims description 7
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- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
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Landscapes
- Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
Abstract
The invention relates to a method for rapidly detecting mifepristone, in particular to a method for detecting mifepristone in medicines. The method comprises the steps that (1) proper amount of medicine to be detected is mixed with an extraction solvent, the mixture is shaken, and extract is obtained; (2) the extract obtained in the step 1 is mixed with sulfuric acid-acetic anhydride reagent, and mixed liquid is obtained; (3) the color change of the mixed liquid obtained in step 2 is observed, if the color of the mixed liquid suddenly changes to obvious yellow, orange yellow and/or orange red, a judgment is made that the medicine possibly contains mifepristone; and if the color of the mixed liquid has no change, a judgment is made that the medicine does not contain mifepristone. The method has the characteristics of accuracy, simplicity, rapidness, low specialty requirement and the like.
Description
Technical field
The invention belongs to medicine detection technique field, relate to a kind of detection method of the real and fake discrimination to the medicine that comprises mifepristone.Be particularly related to a kind of method of fast detecting mifepristone.
Background technology
Mifepristone is a novel anti progestational hormone; It is active not have progestational hormone, estrogen, androgen and antiestrogenic; Can combine with PgR and GCR; Affinity to the endometrium PgR is stronger 5 times than progesterone, and each the phase gestation of animal of becoming pregnant is all had the induced labor effect, can be used as non-operation property contragestive agent.Mifepristone is current domestic common contraceptive and contragestive agent.The mifepristone of taking different dosages can reach different effects, generally, takes mifepristone at every turn and can be used for emergency contraception for 10 to 25 milligrams; Take 150 milligrams of gestation that can stop in 49 days.
The situation that illegal retailer pretends to be the mifepristone sheet with the blank that does not comprise active component appears in recent years, grievous injury consumer's right and health.And such does not have the packing and the regular medicine of counterfeit drug of effective constituent almost as broad as long, if not by breadboard chromatographic apparatus equipment, be difficult to tell truth from falsehood.
" Chinese pharmacopoeia version in 2010 provides the discrimination method of 2 kinds of mifepristone bulk drugs, is respectively ultraviolet spectrophotometry and infra-red sepectrometry, to preparation mifepristone sheet ultraviolet spectrophotometry is provided.These methods all need the professional by Modern Analytical Instrument, only can in the laboratory, just can differentiate.
Therefore; Need a kind of accurately, simple, speed is fast, professional requires the low method of inspection; Whether can identify medicine quickly and accurately is the blank medicine (counterfeit drug that does not promptly conform to the active component mifepristone of counterfeit mifepristone preparation; Generally be the form of tablet) method, improving checkability and accuracy, and can supply non-ly to check professional medicine supervisor to carry out rapid screening at medicine supervision scene.
Summary of the invention
The purpose of this invention is to provide a kind of can be accurately, simple, speed is fast and/or the method for suspecting for the blank medicine of counterfeit mifepristone preparation is detected in the professional lowland that requires.The inventor is surprisingly found out that; Adopt sulfuric acid-aceticanhydride mixing developer to handle this suspected drug; Can be easily check these similar drug goods at the inspection scene of drug market supervision, and method accurately, simple, speed is fast and/or professional require low.The present invention is based on above discovery and be accomplished.
For this reason, first aspect present invention provides a kind of method that detects the mifepristone in the medicine, perhaps a kind of method of suspecting for the medicine of counterfeit mifepristone preparation that detects, and this method may further comprise the steps:
(1) it is an amount of to get said medicine to be checked, and extracts solvent, jolting, extract;
(2) make step (1) extract and sulfuric acid-aceticanhydride reagent mix, get mixed liquor;
(3) observe the change color of step (2) gained mixed liquor,, then judge in this medicine and possibly contain mifepristone if present tangible yellow, orange-yellow and/or orange-red change color suddenly; If the color no change of mixed liquor then can be judged not contain mifepristone in this medicine.
Like this, if step (3) result shows " not containing mifepristone in this medicine ", can assert directly that then it is counterfeit mifepristone preparation; Can be under the situation of necessity further by the for example further judgement of AAS do of other method; The on-the-spot workload of inspection was in time safeguarded market order in accordance with the law when method of the present invention like this can significantly reduce market surveillance.
According to the method for first aspect present invention, wherein said " medicine " is to contain really, indicate and contain any medicine that perhaps possibly contain mifepristone, perhaps has, indicates any medicine that has or possibly have the physiological role of mifepristone really.And according to principle of the present invention; The present invention also comprises the compound preparation that comprises mifepristone that relates to said circumstances; The compound preparation of for example being made up of mifepristone and other one or more active components also can check quickly and easily whether this compound preparation possibly be counterfeit drug by means of the inventive method.
Method according to first aspect present invention; Wherein said " medicine ", " goods ", " the blank medicine of counterfeit mifepristone preparation ", " medicine of counterfeit mifepristone preparation " or " suspect and be the medicine of counterfeit mifepristone preparation "; Their interchangeable in the present invention uses; It comprises that any desire meaning gives mammal for example human any artificial manufactured goods; Artificial mixed goods particularly, it includes but not limited to medicine, health food, food, food additives etc., particularly medicine.In one embodiment, said medicine itself perhaps perhaps contains mifepristone through the form sign of operation instructions through its external packing, perhaps indicates the physiologic function with mifepristone.It will be apparent to those skilled in the art that; Sign contains mifepristone or has the medicine of its physiologic function; It in many cases; For example at commercially available scene, the drug inspection personnel of the public, user, sales force, market surpervision personnel and specialty can't easily judge the physiologic function that whether contains mifepristone in this so-called medicine really or have mifepristone under the situation of instrument, equipment or the method for not passing through specialty.In one embodiment; Said medicine or the similar terms that refers to it are meant a kind of goods; Those skilled in the art (particularly health/health/medicine prison competent authorities or its staff) are subjective or objectively think; Maybe be wittingly in these goods or by mistake do not add the active component mifepristone, thus make these goods not have the physiologic function of mifepristone, for example do not have the effect of contraception.In the present invention; This medicine also can be described as sample, test sample etc.; Those skilled in the art understand the implication that different term had that refers to this medicine according to linguistic context of the present invention, and after for example making this medicine and extracting the solvent jolting, the mixing material that obtains can be called the mixing test solution.In the present invention, this medicine can be states such as solid (for example powder or block, the for example form of tablet), semisolid, liquid.
According to the method for first aspect present invention, extracting solvent described in the step (1) is organic solvent.In one embodiment, described organic solvent includes but not limited to methenyl choloride, methylene chloride or its combination, perhaps contains their other organic solvent.The effect of this extraction solvent is to make the mifepristone dissolving and contacts, mixes, reacts with sulfuric acid-aceticanhydride reagent, and therefore any extraction solution that contains methenyl choloride or methylene chloride of this function of can realizing all is suitable for.In one embodiment, described organic solvent is a methenyl choloride.In one embodiment, described organic solvent is a methylene chloride.According to the method for the invention, in step (1), said medicine needn't be done special restriction with amount and the ratio of extracting solvent, as long as after goods and the extraction solvent, the mifepristone that possibly exist is dissolved in the solvent and reaches the inventive method detectability and gets final product.For example in one embodiment, the extraction solvent in step (1) is 0.1～10ml, for example 0.5～5ml, for example 1～5ml, for example 1～3ml; The amount of the medicine of being got is 0.1～10g for example, for example 0.1～5g; The amount of the medicine of perhaps being got is counted for example 0.01～500mg with mifepristone, for example 0.1～200mg, for example 1～200mg, for example 5～100mg, for example 10～100mg.The detectability of the inventive method is enough to satisfy the scope selection of above embodiment.
According to the method for first aspect present invention, wherein the sulfuric acid described in the step (2)-aceticanhydride reagent is that sulfuric acid and aceticanhydride face with the mix reagent of newly joining.In one embodiment; Said sulfuric acid-aceticanhydride reagent be sulfuric acid with aceticanhydride by 1: the reagent that (0.1～50) volume ratio is mixed; Preferred volume ratio is 1: (1～50), preferred volume ratio are 1: (5～50), preferred volume ratio are 1: (10～50); Preferred volume ratio is 1: (10～30), for example about 1: 20.It will be appreciated by those skilled in the art that sulfuric acid and aceticanhydride can admit of bigger variation range, though may be variant on variable color speed/intensity under some ratio, enforcement of the present invention do not influenced.
According to the method for first aspect present invention, wherein in the step (2), the volume ratio of said sulfuric acid-aceticanhydride reagent and extract is 1: (1～100); Preferred 1: (1～50), preferred 1: (2～25), preferred 1: (5～20); Preferred 1: (5～12), for example about 1: 8, for example about 1: 10.The volume ratio that it will be appreciated by those skilled in the art that sulfuric acid-aceticanhydride reagent and extract can admit of bigger variation range, though may be variant on variable color speed/intensity under some ratio, enforcement of the present invention do not influenced.
According to the method for first aspect present invention, wherein the said sulfuric acid mass percent concentration of step (2) is preferably greater than 95% greater than 90%, and for example about 96%, about 97%, about 98%, about 99%, about 99.5%.According to the method for the invention; Generally speaking; If contain mifepristone in the medicine, use 90% sulfuric acid solution can realize the object of the invention, though the time that chromogenic reaction needs when concentration is low can be longer; And for example reach about 98% the time when concentration is higher, usually in 1 minute, promptly can show typical change color.Therefore, the incorporation time of this step (2) needn't be done special qualification.Because the solution of mifepristone produces pink colour or redness after meeting sulfuric acid-aceticanhydride developer, but color can disappear gradually subsequently, therefore; According to the method for the invention; Step (2) the married operation time should be short as far as possible, as long as reach mixing, observes change color then.Therefore after the soup mixing, can in 1 minute, observe change color, preferably in 30 seconds, observe, for example in 30 seconds, 20 seconds, 15 seconds, 10 seconds, observe change color.
According to the method for first aspect present invention, if said medicine is judged as wherein not conform to mifepristone is arranged, then this medicine can further detect with other method, for example through breadboard method, for example AAS, HPLC method etc.Like this, method of the present invention is specially adapted on market or other detects on-the-spot carry out the more detection and the examination of large sample, and and then reduce breadboard workload; Because the inspection article amount that the inventive method is used is few, help safeguarding businessman's legitimate interests and normal operation.
Based on the method for first aspect present invention, second aspect present invention provides a kind of detection kit, and it is used for detecting suspects for whether the medicine of counterfeit mifepristone preparation contains mifepristone, said kit comprise box body and:
(i) extract solvent, it is packaged in first solvent bottle;
(ii) sulfuric acid, it is packaged in second solvent bottle;
(iii) aceticanhydride; It is packaged in the 3rd solvent bottle; With optional
(iv) the operation instruction data records on it and uses this kit to detect suspection for whether containing the method for operating of mifepristone in the medicine of counterfeit mifepristone preparation.
According to the kit of second aspect present invention, wherein said each solvent bottle is the solvent bottle that can open repeatedly and seal.The material of this solvent bottle is not done special restriction, for example can be the vial that has bottle stopper, bottle cap etc., plastic bottle etc.Three kinds of solvent bottles all can be used for observing change in color, and for this purpose, at least one solvent bottle is that material is preferred with glass.
According to the kit of second aspect present invention, the volume of the extraction solvent of packing in wherein said first solvent bottle accounts for 1/10～9/10 of solvent bottle capacity, and for example 1/10～5/10, for example 1/10～2/10.It is very useful in solvent bottle, reserving certain space; For example can directly goods to be checked directly be joined in the solvent bottle, cover completely, then jolting; Goods to be checked are fully mixed with the extraction solvent, be dissolved in the solution to make the active component that possibly exist as much as possible; Kit provided by the invention like this is very simple.
Kit according to second aspect present invention; In wherein said second solvent bottle and the 3rd solvent bottle; The residual capacity of at least one solvent bottle (promptly not filling the space of test solution) is enough to fill the solution of another solvent bottle, and this residual capacity enough makes two kinds of solution mix in use.For example the residual capacity of second solvent bottle is 1.5～10 times of required aceticanhydride liquid volume, and making has enough spaces to make the two mixing when being poured into aceticanhydride in the sulfuric acid.
Kit according to second aspect present invention; In wherein said first solvent bottle, second solvent bottle and the 3rd solvent bottle; The residual capacity of at least one solvent bottle (promptly not filling the space of test solution) is enough to fill the solution of two other solvent bottle, and this residual capacity enough makes three kinds of solution mix in use.For example, the residual capacity of first solvent bottle is 1.5～10 times of volume of required sulfuric acid-aceticanhydride reagent, and making has enough spaces that their are mixed sulfuric acid-aceticanhydride reagent when being poured in the extract.Again for example, the residual capacity of second solvent bottle is 1.5～10 times of required sulfuric acid-aceticanhydride-extraction solution three volume total amount, and making has enough spaces that they are mixed when being poured into extract in sulfuric acid-aceticanhydride reagent.
According to the kit of second aspect present invention, wherein can also comprise the 4th solvent bottle, its capacity is enough to filling needle to a required sulfuric acid-aceticanhydride-extraction solution three volume total amount of inspection article, for example is 1.5～10 times of this volume total amount.For example in one embodiment; Medicine joined to extract in the solvent bottle extract, in addition the aceticanhydride in sulfuric acid in second solvent bottle and the 3rd solvent bottle is mixed, again extract and sulfuric acid-aceticanhydride reagent are poured into respectively in the 4th solvent bottle; They are mixed, and observe change color.
Kit according to second aspect present invention; Extraction solvent in wherein said first solvent bottle, the sulfuric acid in second solvent bottle, the aceticanhydride in the 3rd solvent bottle; They are can supply repeatedly to check required amount independently of one another, thereby make kit of the present invention become a kind of multiple dose kit.According to spirit of the present invention, the various configurations of these multiple dose kits and modification can be implemented easily by those skilled in the art, and these various configurations and modification are all within the spirit and scope of the present invention.According to these embodiments, the invention provides can be in the same place or the different location detect the kit of a plurality of goods material requesteds.
Kit according to second aspect present invention; Wherein said operation instruction data can be to use instructions, detection method explanation, detect criterion or the like; Its form can be the paper that is printed with corresponding information, card etc., and this operation instruction data has been put down in writing the described method of first aspect present invention basically.Therefore, in the arbitrary embodiment of first aspect present invention, arbitrary technical characterictic wherein is equally applicable to the kit of second aspect present invention or is applicable to others of the present invention.
Third aspect present invention provides a kind of information detail file, has wherein put down in writing each described method of first aspect present invention basically.
In one embodiment, this information detail file is to be the following form that is selected from: paper document (including but not limited to file single page, pamphlet, publication), magnetic medium, CD, floppy disk, electronic publication, Web publishing etc., and their combination.
Fourth aspect present invention provides according to third aspect present invention information detail file and has detected the method for whether closing mifepristone in the medicine of counterfeit mifepristone preparation of suspecting.
Fifth aspect present invention provides a kind of goods, and its sign contains mifepristone, but be to use these goods of the said information detail file detection of the said method of first aspect present invention, the said kit of second aspect and/or third aspect demonstration not conform to mifepristone is arranged.
Arbitrary embodiment of arbitrary aspect of the present invention can make up with other embodiment, as long as they contradiction can not occur.In addition, in the arbitrary embodiment aspect the present invention is arbitrary, arbitrary technical characterictic goes for this technical characterictic in other embodiment, as long as they contradiction can not occur.
Do further description in the face of the present invention down.
All documents that the present invention quoted from, their full content is incorporated this paper by reference into, and if the expressed implication of these documents and the present invention when inconsistent, be as the criterion with statement of the present invention.In addition; Various terms and phrase that the present invention uses have the general sense of well known to a person skilled in the art; Nonetheless; The present invention still hopes at this more detailed explanation and explanation to be done in these terms and phrase, and term of mentioning and phrase are as the criterion with the implication that the present invention was explained if any inconsistent with known implication.
The term " suspection " that this paper uses can be because of subjective factor or odjective cause; The people is thought indicate the goods (for example medicine) that contain mifepristone or have its physiologic function; Its product quality and its sign inconsistent; Particularly possibly not contain mifepristone, blank or counterfeit drug that promptly common people are said.
The term " sxemiquantitative " that this paper uses is meant that this quantitative result is rough, is not accurate quantification.
The term " quantitative limit " that this paper uses is meant when content is lower than this limit, can not be quantitative.
The term " sulfuric acid-aceticanhydride reagent " that this paper uses also can be described as sulfuric acid-aceticanhydride developer or developer, and it is obtained facing with preceding mixing by sulfuric acid and aceticanhydride.
In one embodiment of the invention, can also be equipped with test tube in the said kit.
Extraction solvent according to the invention can be methenyl choloride or methylene chloride, or any mixed solvent that can dissolve mifepristone that contains methenyl choloride or methylene chloride.For many mifepristone preparations, wherein contain more auxiliary material, can not dissolve these auxiliary materials and extract the solvent majority, therefore, step in the inventive method (1) gained extract possibly be a kind of suspension.According to the method for the invention, step (1) gained extract needn't filter and promptly can be used for next step, and this has simplified operation steps greatly, also is specially adapted to the processing of minute quantity sample.
Therefore, in the preferred embodiment of first aspect present invention, a kind of method of suspecting for the medicine of counterfeit mifepristone preparation that detects is provided, this method may further comprise the steps:
(1) sample thief adds and extracts solvent 1～2ml, and jolting 1 minute;
(2) sample solution need not to filter, and the developer that sulfuric acid-aceticanhydride is formed mixes with step (1) gained sample solution;
(3) in 10 seconds, observe the change color of step (2) gained mixed liquor,, then judge in this medicine and possibly contain mifepristone if present tangible yellow, orange-yellow and/or orange-red change color suddenly; If the color no change of mixed liquor then can be judged not contain mifepristone in this medicine.
In another preferred embodiment of first aspect present invention, a kind of method of suspecting for the medicine of counterfeit mifepristone preparation that detects is provided, this method may further comprise the steps:
(1) (mifepristone that contains sign is 5～100mg) to add and extract solvent methenyl choloride 2ml to sample thief, and jolting 1 minute;
(2) need not to filter, the volume ratio that directly will newly join is that sulfuric acid-about 0.25ml of aceticanhydride developer of 1: 20 mixes with the extract of step (1);
(3) in 10 seconds, observe the change color of step (2) gained mixed liquor,, then judge in this medicine and possibly contain mifepristone if present tangible yellow, orange-yellow and/or orange-red change color suddenly; If the color no change of mixed liquor then can be judged not contain mifepristone in this medicine.
For overcoming the deficiency of prior art, the present invention provides a kind of method of discerning the false from the genuine fast of mifepristone medicine, can be used for judging whether medicine is the blank of counterfeit mifepristone.The present invention compares with the method for quick of other mifepristone medicine, has following advantage:
(1) speed is fast: sample of the present invention need not steps such as filtration after dissolving, can judge the result at the adding developer in 10 seconds, detects about 3 minutes only consuming time of overall process.And additive method detection overall process wants consuming time more than 45 minutes at least.
(2) easy and simple to handle: compare the inventive method with other method and need not to filter, it is few to detect step, operates easier.
(3) result is accurate: the inventive method colour developing phenomenon is obvious, and antijamming capability is strong, and the result is accurate.
(4) applicability is strong: the present invention is simple to operate, and operating environment is not had specific (special) requirements, and the result judges that phenomenon is obvious, need not to possess the professional technique experience, and the supervisor who is suitable for non-check specialty supervises execute-in-place at medicine.
(5) highly sensitive: the present invention is highly sensitive, can reach 0.25mg/ml at least to the detection sensitivity of mifepristone, and the tablet of a minimum dose can satisfy the detection requirement.
When the embodiment of the present invention method, following aspect is also considered within the spirit and scope of the present invention:
The points for attention of the method for quick identification of a kind of mifepristone provided by the invention are following:
(1) for example chloroform soln generation after meeting sulfuric acid-aceticanhydride developer is yellow or orange-yellow for the solution of mifepristone; But color can disappear gradually subsequently; Event need be observed the variation of solution colour in 30 seconds (preferred 20 seconds, preferred 10 seconds) after adding developer.
(2) sulfuric acid-aceticanhydride developer is owing to can be rotten after placing for a long time, so must face with newly joining.
(3) though along with the increase color developing effect of sulfuric acid-aceticanhydride developer consumption can be more obvious, simultaneously the sample solution temperature also can raise, thus the developer consumption should be controlled at the sample solution volume 1/2 in.Preferably, the volume ratio of sulfuric acid-aceticanhydride reagent and extract is 1: (1～100), preferred 1: (1～50), preferred 1: (2～25), preferred 1: (5～20), for example about 1: 10.。
Embodiment
Further specify the present invention through concrete instance below, still, be to be understood that into, these instances are only used for the usefulness of explanation more in detail particularly, are used for limiting in any form the present invention and should not be construed as.
The present invention carries out generality and/or concrete description to the material and the test method that are used in the test.Though for realizing that employed many materials of the object of the invention and method of operating are well known in the art, the present invention still does to describe in detail as far as possible at this.It will be apparent to those skilled in the art that hereinafter, if do not specify that material therefor of the present invention and method of operating are well known in the art.In following test, like not explanation in addition, the sulfuric acid of mentioning is meant that concentration is 98% sulfuric acid.
In following test, like not explanation in addition, the extraction solvent in the step of mentioning (1) is for example 2ml, and the sulfuric acid of mentioning-aceticanhydride reagent is sulfuric acid and 1: 20 by volume potpourri of aceticanhydride, and the volume ratio of the sulfuric acid of mentioning-aceticanhydride reagent and extract is 1: 8.
Whether embodiment 1, detection medicine contain the general operational requirement(GOR) of mifepristone
1, sampling amount
Dissimilar samples are recommended sampling as follows:
| Sample type | Sampling amount |
| Raw material | 5mg-20mg |
| 10mg specification tablet | Get 2, grind |
| 25mg specification tablet | Get 1, grind |
| 200mg specification tablet | Get half sheet, grind |
The amount that this shows the article to be checked that the inventive method is used is considerably less, so that damage not guilty operator's interests less as far as possible.
2, need testing solution preparation
The article of getting it filled add organic solvent (using methenyl choloride in the following test) 2ml after grinding, and jolting got final product in 1 minute, need not to filter.
3, operation steps:
(1) (mifepristone that contains sign is 5～100mg) to add and extract solvent methenyl choloride 2ml to sample thief, and jolting 1 minute;
(2) need not to filter, the volume ratio that directly will newly join is that sulfuric acid-about 0.25ml of aceticanhydride developer of 1: 20 mixes with the extract of step (1);
(3) in 10 seconds, observe the change color of step (2) gained mixed liquor,, then judge in this medicine and possibly contain mifepristone if present tangible yellow, orange-yellow and/or orange-red change color suddenly; If the color no change of mixed liquor then can be judged not contain mifepristone in this medicine.
4, colour developing and judged result
Sulfuric acid-aceticanhydride mixing developer and above sample mix with the new preparation of 0.2ml through organic solvent extraction; In 10 seconds, observe; If present tangible yellow, orange-yellow and/or orange-red change color suddenly, then judge in this medicine and possibly contain mifepristone; If the color no change of mixed liquor then can be judged in this medicine not conform to mifepristone.Then in case of necessity, to containing and/or not contain the sample collecting greater amount of mifepristone, prepare to use the for example further judgement of AAS do of other method.
Whether contain the test of mifepristone in embodiment 2, the detection medicine
Adopt the method for embodiment 1; Detecting 20 batches of commercially available samples (comprises and indicates single preparations of ephedrine and the raw material that contains mifepristone; Omit manufacturer and product batch number, represent with sequence number), and with reference to the HPLC method chromatographic condition under the related substance item of " Chinese Pharmacopoeia 2005 version two ones " mifepristone raw material; Use LCMS method test sample, specific as follows:
The according to the form below sample thief adds methenyl choloride 2ml, jolting 1 minute.Sulfuric acid-aceticanhydride mixing developer with the new preparation of 0.2ml is added in the sample solution then, in 10 seconds, observes, if sample solution presents tangible yellow, orange-yellow and/or orange red suddenly, then can judge in the sample and possibly contain mifepristone; If sample solution color no change then can be judged not contain mifepristone in the sample.Adopt mass spectroscopy to verify that the result is following simultaneously:
#: each sample is the different production firms that obtain of pharmacy or health products shop or other approach from the market and/or the medicine or the bulk drug of different size and/or different batches, and suspection possibly not contain mifepristone or not be mifepristone.
* contain: express possibility and contain mifepristone, show that with the inventive method this part sample that possibly contain mifepristone can be further through the for example further checking of AAS do of other method; Do not contain: expression does not contain mifepristone.
Visible by result in the table, showing that yellow, orange-yellow or orange-red change color shows possibly contain mifepristone, and along with the drug concentration increase color appear yellow-＞orange-yellow-＞orange red gradually dark variation.
The checking of above-mentioned experimental result and second order ms is the result show, the positive report of none official holiday of detection method of the present invention, and the also any sample that contains mifepristone of omission not simultaneously, the result is accurately and reliably.
In addition; Measure 6 samples that above-mentioned detection does not contain mifepristone by the described sampling of the inventive method, and mix mifepristone raw material 10mg respectively, experimentize by the inventive method; It is yellow that the result all is in 10 seconds; Show that this method has good antijamming capability, specificity is strong, and good accuracy is arranged.
Further, use three kinds of mifepristone sheets of sequence 1,5,10 in the above table to make an experiment respectively.In first group of test, extract solvent and be 1 or 5ml, other is operated with embodiment 1; In second group of test, sulfuric acid-aceticanhydride reagent is sulfuric acid and aceticanhydride is prepared in the ratio of 1: 10 or 1: 30, and other is operated with embodiment 1; In the 3rd group of test, the volume ratio of sulfuric acid-aceticanhydride reagent and extract is 1: 5 or 1: 20, and other is operated with embodiment 1.In these tests, change color all with last table in the result similar, approaching or identical.
The performance of embodiment 3, the inventive method
Present embodiment is investigated the LDL of inventive method to detection mifepristone reference substance and sample, and is specific as follows:
Get the mifepristone reference substance 10mg that Chinese pharmaceutical biological product identification research institute provides, add the methenyl choloride dissolving and be diluted to the solution that contains the 0.25mg mifepristone among every 1ml.Sulfuric acid-aceticanhydride mixing developer with the new preparation of 0.2ml is added in the sample solution then, and it is yellow that sample solution was in 10 seconds.
Get 10mg specification mifepristone sheet, porphyrize adds the methenyl choloride dissolving and is diluted to the solution that contains the 0.25mg mifepristone among every 1ml.Sulfuric acid-aceticanhydride mixing developer with the new preparation of 0.2ml is added in the sample solution then, and it is yellow that sample solution was in 10 seconds.
According to above-mentioned experimental result, can judge that the sensitivity of the inventive method detection mifepristone can reach 0.25mg/ml at least.And the 10mg mifepristone sheet of minimum gauge is under testing conditions of the present invention, and the concentration of mifepristone is 5mg/ml, is 20 times of this method LDL, so the sensitivity of this method can reach the actual needs of the blank that detects the personation mifepristone fully.
The present invention has done detailed explanation to various aspects of the present invention through preceding text, states these specific embodiments yet the present invention is not limited to this, and the spirit and scope of the present invention should be as the criterion with appended claims.The inventive method does not need filtered sample solution, detects overall process about 3 minutes only consuming time, has advantages such as quick, easy, sensitivity height, can effectively detect whether contain mifepristone in the suspected drug.
Claims (10)
1. the method for the mifepristone in the detection medicine, this method may further comprise the steps:
(1) it is an amount of to get said medicine to be checked, and extracts solvent, jolting, extract;
(2) make step (1) extract and sulfuric acid-aceticanhydride reagent mix, get mixed liquor;
(3) observe the change color of step (2) gained mixed liquor,, then judge in this medicine and possibly contain mifepristone if present tangible yellow, orange-yellow and/or orange-red change color suddenly; If the color no change of mixed liquor then can be judged not contain mifepristone in this medicine.
2. according to the process of claim 1 wherein that extracting solvent described in the step (1) is organic solvent; Include but not limited to methenyl choloride, methylene chloride or its combination, perhaps contain their other organic solvent.
3. according to the process of claim 1 wherein that the sulfuric acid described in the step (2)-aceticanhydride reagent is that sulfuric acid and aceticanhydride face with the mix reagent of newly joining.
4. according to the method for claim 3, said sulfuric acid-aceticanhydride reagent be sulfuric acid with aceticanhydride by 1: the reagent that (0.1～50) volume ratio is mixed.
5. according to the process of claim 1 wherein that in the step (2), the volume ratio of said sulfuric acid-aceticanhydride reagent and extract is 1: (1～100).
6. detection kit, it is used for detecting suspects for whether the medicine of counterfeit mifepristone preparation contains mifepristone, said kit comprise box body and:
(i) extract solvent, it is packaged in first solvent bottle;
(ii) sulfuric acid, it is packaged in second solvent bottle;
(iii) aceticanhydride; It is packaged in the 3rd solvent bottle; With optional
(iv) the operation instruction data records on it and uses this kit to detect suspection for whether containing the method for operating of mifepristone in the medicine of counterfeit mifepristone preparation.
7. according to the kit of claim 6, it is characterized in that:
Said each solvent bottle is the solvent bottle that can open repeatedly and seal, preferably vial;
The volume of the extraction solvent of packing in said first solvent bottle accounts for 1/10～9/10 of solvent bottle capacity;
In said second solvent bottle and the 3rd solvent bottle, the residual capacity of at least one solvent bottle is enough to fill the solution of another solvent bottle, and this residual capacity enough makes two kinds of solution mix in use;
In said first solvent bottle, second solvent bottle and the 3rd solvent bottle, the residual capacity of at least one solvent bottle is enough to fill the solution of two other solvent bottle, and this residual capacity enough makes three kinds of solution mix in use;
Wherein can also comprise the 4th solvent bottle, its capacity is enough to filling needle to a required sulfuric acid-aceticanhydride-extraction solution three volume total amount of inspection article;
Extraction solvent in said first solvent bottle, the sulfuric acid in second solvent bottle, the aceticanhydride in the 3rd solvent bottle, they are to supply repeatedly to check required amount independently of one another; And/or
Said operation instruction data has been put down in writing each described method of claim 1 to 5 basically.
8. an information detail file has wherein been put down in writing each described method of claim 1 to 5 basically.
9. according to Claim 8 information detail file, it is to be the following form that is selected from: paper document (including but not limited to file single page, pamphlet, publication), magnetic medium, CD, floppy disk, electronic publication, Web publishing etc., and their combination.
10. goods, its sign contains mifepristone, shows that these goods do not contain mifepristone but use each said method of claim 1-9, kit and/or information detail file to detect.
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