CN103630628B - Method used for detecting formic acid residue in imidazole vermifuges - Google Patents
Method used for detecting formic acid residue in imidazole vermifuges Download PDFInfo
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Abstract
The invention relates to the technical field of formic acid solvent residue detection, in particular to a method used for detecting formic acid residue in imidazole vermifuges. The method comprises the following steps: by using a derivatization technology, the formic acid is dissolved in a methyl sulfoxide solvent and reacts with methanol under the catalysis of sulfuric acid to generate methyl formate, and then a headspace sampling method is adopted to measure the methyl formate, so as to measure the formic acid residue. The method has the benefits that by selecting methyl sulfoxide as the solvent for detecting the formic acid residue, the problem that imidazole vermifuges can not dissolve in common solvents such as alcohol, ketone and esters solvent is solved; the derivatization reagent is improved; by replacing ethanol with the methanol, the esterification activity is relatively high, the derivatization reaction conversion rate is improved, and finally, the detection accuracy for the formic acid residue is improved; the concentration of the formic acid residue within detection range is good in linear relationship by adopting a headspace gas-chromatography method. Therefore, the method has the advantages that the operation is simple and convenient, the separation degree is good, the sensitivity is high, the repeatability is good, the data is accurate and reliable, and the like.
Description
Technical field
What the present invention relates to is a kind of formic acid solvent residue detection technical field, specifically a kind of for detecting the method that in Anthelmintic imidazoles, formic acid is residual.
Background technology
Need to use formic acid as solvent in Anthelmintic imidazoles (comprising albendazole, mebendazole, Flubendazole, Fenbendazole, oxfendazole, Oxibendazole, Luxabendazole, thiabendazole) subtractive process more, ICH regulation formic acid is three kind solvents, limit is 0.5%, for strictly controlling its residual quantity.In addition, formic acid remains the stability that also can affect mebendazole, thus affects product quality and drug effect.
Because formic acid character is active, there is stronger acidity, corrosivity and reductibility, and molecular weight, go out the features such as peak response is low, directly measure more difficult.The assay method of current formic acid has vapor-phase chromatography, liquid phase chromatography, the chromatography of ions etc., wherein conventional with vapor-phase chromatography, (the chromatograms such as Wang Hua in 2006,2006,24 (4): 418) micro-formic acid in non-derived vapor-phase chromatography Fast Measurement glacial acetic acid is reported, and Wu little Ying (Anhui medicine in 2012,2012,16 (3)) report Analysis of Formic acid Residual in capillary gas chromatography Calcipotriol, adopt esterification process that formic acid is derivatized to ethyl formate and detect, the response of remarkable improvement in FID, and peak type is symmetrical.In addition, Ren Xinan in 2007 etc. (Hebei chemical industry, 2007,30 (8)) report Analysis of Formic acid Residual in Theophylline by Liquid Chromatography.
Because the chromatography of ions need use specific instrument, and in liquid chromatography, it is very fast that formic acid goes out peak, can be subject to the interference of solvent peak, because formic acid responds very low in FID, testing requirement cannot be met, although adopt esterification process that formic acid is derivatized to ethyl formate to detect, significantly improve the response in FID, adopt ethanol as solvent, derivatization conversion ratio is not high, causes the precision of formic acid residue detection not high.Adopt ECD detecting device also not improve, although adopt MS detecting device to detect, experimental cost is larger.
In addition, Anthelmintic imidazoles is insoluble in conventional alcohols, ketone, esters solvent, require to select suitable dissolution with solvents Anthelmintic imidazoles carry out the detection of formic acid residual solvent and can not accuracy of detection be affected, for this reason, the data that in a kind of applicable Anthelmintic imidazoles, formic acid remains accurately and reliably, the low detection method of experimentation cost needs further exploratory development.
Summary of the invention
The object of the invention is to: for the various shortcoming of above-mentioned detection method, provide a kind of easy and simple to handle, degree of separation good, highly sensitive, reproducible, the data detection method that formic acid is residual in Anthelmintic imidazoles accurately and reliably.
For achieving the above object, the technical solution used in the present invention is as follows:
For detecting the method that in Anthelmintic imidazoles, formic acid is residual, this detection method comprises the following steps:
(1) solution preparation: be dissolved in by Anthelmintic imidazoles in dimethyl sulfoxide, adds sulfuric acid and is mixed with dilute solution, then prepares test liquid, standard reserving solution respectively and shine product solution;
(2) vapor detection: adopt headspace injection method to measure methyl formate, and then reach the mensuration residual to formic acid, its testing conditions and parameter as follows: carrier gas: nitrogen, constant voltage: 95 ~ 120kPa, injector: bypass flow 10 ~ 30ml/min, temperature 180 ~ 250 DEG C, detecting device: hydrogen flame ion detector, detector temperature: 250 ~ 300 DEG C, head-space sampler bath temperature: 50 ~ 80 DEG C, head-space sampler quantitative loop temperature: 180 ~ 250 DEG C, head-space sampler transfer conduit temperature: 180 ~ 250 DEG C, head-space sampler sample injection bottle equilibration time: 15 ~ 30min.
Further, described solution preparation comprises the steps:
(1) 2.5%(v/v is prepared) dimethyl sulfoxide (DMSO) solution of sulfuric acid is dilute solution;
(2) precision takes Anthelmintic imidazoles sample 200.0mg and enters 20ml headspace sampling bottle, adds 0.1ml methyl alcohol, then pipettes 2ml dilute solution and make test liquid;
(3) pipette 10ul formic acid in 50ml volumetric flask, be diluted to scale with dilute solution, shake up the standard reserving solution being mixed with 2000ppm;
(4) in 50ml volumetric flask, add about 20ml dilute solution, precision pipettes 25ml standard reserving solution, and dilute solution is settled to scale, accurately pipettes 2ml and enters 20ml headspace sampling bottle, then add 0.1ml methyl alcohol, make reference substance solution.
Further, described vapor detection comprises the steps:
(1) get reference substance solution and carry out gas Chromatographic Determination, record chromatogram, get the formic acid duplicate measurements of variable concentrations for several times, record chromatographic peak area, draw the peak area of methyl formate and the graph of a relation of formic acid concn, line linearity matching of going forward side by side, obtain linear equation Y=a X+b
A-slope
B-intercept
Peak area in Y-contrast liquid after methyl formate correction
The concentration (ppm, sample marker amount is 200mg) of formic acid in X-contrast liquid;
(2) according to step (1), reappearance is carried out to formic acid reference substance solution;
(3) according to step (1), need testing solution is detected, by the peak area value after correction by formic acid concn X in following formulae discovery test sample;
The concentration (ppm) of target solvent in X-sample
The corrected value of target solvent peak area in Y-test liquid
The sample weighting amount (mg) of sample in Wa-test liquid
200.0-sample marker amount (mg).
Further, testing conditions and the parameter of described detection method are as follows: carrier gas: nitrogen, constant voltage: 95 ~ 120kPa, injector: bypass flow 15 ~ 20ml/min, temperature 200 ~ 250 DEG C, detecting device: hydrogen flame ion detector, detector temperature: 290 ~ 300 DEG C, head-space sampler bath temperature: 50 ~ 60 DEG C, head-space sampler quantitative loop temperature: 180 ~ 220 DEG C, head-space sampler transfer conduit temperature: 180 ~ 220 DEG C, head-space sampler sample injection bottle equilibration time: 15 ~ 25min.
Further, testing conditions and the parameter of described detection method are as follows: carrier gas: nitrogen, constant voltage: 100kPa, injector: bypass flow 20ml/min, temperature 250 DEG C, detecting device: hydrogen flame ion detector, detector temperature: 290 DEG C, head-space sampler bath temperature: 55 DEG C, head-space sampler quantitative loop temperature: 200 DEG C, head-space sampler transfer conduit temperature: 200 DEG C, head-space sampler sample injection bottle equilibration time: 15min.
Further, the capillary column model of the gas chromatograph adopted in described vapor detection is HP-INNOWax(30m × 0.32mm × 0.5um), varian CP-SIL5CB(50m × 0.32mm × 5um), FFAP(30m × 0.32mm × 1um), OV-17(25m × 0.25mm × 0.5um), AgilentDB624(25m × 0.25mm × 2.55um) in any one.
Further, in described vapor detection, the temperature of detecting device adopts programmed temperature method, the initial temperature of described programmed temperature method is 40 DEG C, heating rate 1 is 5 ~ 10 DEG C/min, finishing temperature 1 is 75 DEG C, and keep the follow-up temperature of continuing rising of 0 ~ 5min, heating rate 2 is 30 ~ 50 DEG C/min, finishing temperature 2 is 180 ~ 250 DEG C, and temperature hold-time 2 is 8 ~ 10min.
Further, the detection of described formic acid is limited to 5-15ppm.
Further, described formic acid be quantitatively limited to 10-30ppm.
Further, described imidazoles comprises: albendazole, mebendazole, Flubendazole, Fenbendazole, oxfendazole, Oxibendazole, Luxabendazole, thiabendazole.
The beneficial effect of technical scheme of the present invention is adopted to be:
1, have selected the solvent of dimethyl sulfoxide (DMSO) as formic acid residue detection, solve problem insoluble in alcohols that Anthelmintic imidazoles commonly uses, ketone, esters solvent.
2, improve derivatization reagent, methyl alcohol is replaced ethanol, esterification activity is higher, improves the conversion ratio of derivative reaction, finally improves the precision of formic acid residue detection.
3, good in investigation scope internal linear relation with headspace gas chromatography formic acid residual concentration.
4, this law have easy and simple to handle, degree of separation good, highly sensitive, reproducible, the data advantage such as accurately and reliably.
Accompanying drawing explanation
Fig. 1 is specificity test gas chromatography spectrogram.
Fig. 2 is the linear graph of methyl formate peak area to formic acid concn.
Embodiment
Following by specific embodiment, be described in detail the present invention, following examples are for explaining the present invention, instead of limitation of the present invention.
Method validation has carried out specificity, linear and scope, system reappearance, Intermediate precision mensuration, detectability, quantitative limit, accuracy, analysis reappearance, stability, serviceability test.
Embodiment 1
1, condition determination and parameter:
The capillary column (HP-INNOWax(30m × 0.32mm × 0.5um) of gas chromatograph).
Carrier gas: nitrogen, constant voltage: 100kPa, the bypass flow of injector: 20ml/min, the temperature of injector: 250 DEG C, detecting device: hydrogen flame ion detector (FID), detector temperature: 290 DEG C, hydrogen: 25ml/min, air: 400ml/min
Column temperature: temperature programme (programmed analysis)
| Initial temperature | 40℃ |
| The initial temperature retention time | 0.5min |
| Heating rate 1 | 8℃/min |
| Finishing temperature 1 | 75℃ |
| Temperature hold-time 1 | 0min |
| Heating rate 2 | 40℃/min |
| Finishing temperature 2 | 230℃ |
| Temperature hold-time 2 | 8.3min |
Head-space sampler: bath temperature: 55 DEG C
Quantitative loop temperature: 200 DEG C
Transfer conduit temperature: 200 DEG C
Sample injection bottle equilibration time: 15min
2, specificity test
(1) solution preparation:
1. 2.5%(v/v is prepared) dimethyl sulfoxide (DMSO) solution of sulfuric acid is dilute solution, precision takes Anthelmintic imidazoles sample 200.0mg and enters 20ml headspace sampling bottle, adds 0.1ml methyl alcohol, then pipettes 2ml dilute solution and make test liquid; Pipette 10ul formic acid in 50ml volumetric flask, be diluted to scale with dilute solution, shake up the standard reserving solution being mixed with 2000ppm; In 50ml volumetric flask, add about 20ml dilute solution, precision pipettes 25ml standard reserving solution, and dilute solution is settled to scale, accurately pipettes 2ml and enters 20ml headspace sampling bottle, then add 0.1ml methyl alcohol, make reference substance solution;
2. specificity solution: add about 20ml dilute solution in 25ml volumetric flask, draws 12.5l formic acid with micro syringe and adds this volumetric flask, be settled to scale, shake up with dilute solution.Accurately pipette in this solution 10ml to 25ml volumetric flask, be settled to scale with dilute solution, shake up.The standard reserving solution accurately pipetting 12.5ml2000ppm again enters in 25ml volumetric flask, is settled to scale with dilute solution.
(2) operation steps: accurately pipette 2ml specificity solution and enter 20ml headspace sampling bottle, then add 0.1ml methyl alcohol, seal.
Corresponding collection of illustrative plates refers to accompanying drawing 1
| Solvent title | Retention time RT/min |
| Methyl formate | 6.033 |
3, linear and scope test
(1) reference substance solution preparation:
1. 5000ppm solution: add about 20ml dilute solution in 25ml volumetric flask, draws 12.5l formic acid with micro syringe and adds this volumetric flask, be settled to scale, accurately pipette 2ml and enter sample injection bottle, then add 0.1ml methyl alcohol, seal with dilute solution.
2. 2000ppm solution: add about 20ml dilute solution in 25ml volumetric flask, pipettes 10ml and enters this volumetric flask, be settled to scale with dilute solution, accurately pipettes 2ml and enters 20ml headspace sampling bottle, then add 0.1ml methyl alcohol, seal.
3. 1000ppm solution: accurately pipette 12.5ml2000ppm solution and enter in 25ml volumetric flask, be settled to scale with dilute solution, accurately pipettes 2ml and enters 20ml headspace sampling bottle, then add 0.1ml methyl alcohol, seal.
4. 200ppm solution: accurately pipette 5ml1000ppm solution and enter in 25ml volumetric flask, be settled to scale with dilute solution, accurately pipettes 2ml and enters 20ml sample injection bottle, then add 0.1ml methyl alcohol, seal.
5. 100ppm solution: accurately pipette 5ml200ppm solution and enter in 10ml volumetric flask, be settled to scale with dilute solution, accurately pipettes 2ml and enters 20ml headspace sampling bottle, then add 0.1ml methyl alcohol, seal.
(2) operation steps:
1000ppm enters 6 pins, and 100ppm, 5000ppm enter 3 pins, and the solution of other each concentration enters 1 pin.
(3) testing result is as follows:
Draw peak area to the figure of formic acid concn, linear fit, Line Chart is shown in accompanying drawing 2.
4, system reappearance test
Prepare 6 parts of Duplicate Samples according to the 1000ppm solution preparation method in linear and scope test, each Duplicate Samples enters 1 pin.
Test figure is as follows:
5, detectability test
(1) solution preparation:
Be that solution in 3.0 pairs of linear tests dilutes according to signal to noise ratio (S/N ratio) (S/N).
(2) operation steps:
Accurately pipette the above-mentioned solution of 2ml and enter 20ml headspace sampling bottle, then add 0.1ml methyl alcohol, seal.Each solution enters a pin.
Test figure is as follows:
Detectability concentration (ppm) is assessed by calculated signal to noise ratio (S/N ratio) above:
Detectability=concentration × 3/ signal to noise ratio (S/N ratio)
6, quantitative limit test
(1) solution preparation:
Be that solution liquid in 10.0 pairs of linear tests dilutes according to signal to noise ratio (S/N ratio) (S/N), obtain quantitative limit solution.
(2) operation steps:
Accurately pipette each quantitative limit solution of 2ml and enter 20ml headspace sampling bottle, then add 0.1ml methyl alcohol, seal.Prepare five parts of Duplicate Samples.
Test figure is as follows:
Quantitative limit concentration (ppm) is assessed by calculated signal to noise ratio (S/N ratio) above:
Quantitative limit=concentration × 10/ signal to noise ratio (S/N ratio)
7, recovery test
Take 200.0mg and enter 20ml headspace sampling bottle for sample, add 2ml10ppm, 50ppm, 100ppm, 500ppm solution respectively, then add 0.1ml methyl alcohol, seal.
Recovery test result is as follows:
| Concentration/ppm | The single needle recovery | Average recovery rate |
| 10 | 95.9%117.6%108.4% | 107.3% |
| 50 | 91.1%92.1%101.7% | 94.9% |
| 1000 | 97.8%98.1%99.3% | 98.4% |
| 2000 | 96.6%99.1%97.9% | 97.9% |
8, reappearance test is analyzed
Take 200.0mg and enter 20ml headspace sampling bottle for sample, add 2ml50ppm, 1000ppm, 2000ppm solution respectively, then add 0.1ml methyl alcohol, seal.
Test findings is as follows:
| 50ppm testing result | 1000ppm testing result | 2000ppm testing result | |
| 1 | 59 | 1141 | 2510 |
| 2 | 59 | 1116 | 2576 |
| 3 | 66 | 1189 | 2545 |
| Mean value | 61 | 1149 | 2544 |
| RSD% | 6.6 | 3.2 | 1.3 |
9, formic acid residue detection in Flubendazole bulk drug
Adopt derivatization method to be dissolved in dimethyl sulfoxide by Anthelmintic imidazoles, adopt Derivative, react with methyl alcohol under sulfuric acid catalysis and generate methyl formate, adopt headspace injection method to measure methyl formate, and then reach the mensuration residual to formic acid.
| Sample lot number | Testing result (ppm) | |
| 1 | 1P0191309001 | 45 |
| 2 | 1P0191309002 | 51 |
| 3 | 1P0191309003 | 43 |
| 4 | 1P0191309004 | 46 |
| 5 | 1P0191309005 | 38 |
| 6 | 1P0191309006 | 42 |
Have selected the solvent of dimethyl sulfoxide (DMSO) as formic acid residue detection, solve problem insoluble in alcohols that Anthelmintic imidazoles commonly uses, ketone, esters solvent; Improve derivatization reagent, methyl alcohol is replaced ethanol, esterification activity is higher, improves the conversion ratio of derivative reaction, finally improves the precision of formic acid residue detection; Good in investigation scope internal linear relation with headspace gas chromatography formic acid residual concentration.
Embodiment 2
1, condition determination and parameter:
The capillary column (varian CP-SIL5CB50m × 0.32mm × 5 μm) of gas chromatograph.
Carrier gas: nitrogen, constant voltage: 95kPa, the bypass flow of injector: 10ml/min, the temperature of injector: 180 DEG C, detecting device: hydrogen flame ion detector (FID), detector temperature: 250 DEG C, hydrogen: 25ml/min, air: 400ml/min
Column temperature: temperature programme (programmed analysis)
| Initial temperature | 40℃ |
| The initial temperature retention time | 0.5min |
| Heating rate 1 | 5℃/min |
| Finishing temperature 1 | 75℃ |
| Temperature hold-time 1 | 0min |
| Heating rate 2 | 30℃/min |
| Finishing temperature 2 | 180℃ |
| Temperature hold-time 2 | 8min |
Head-space sampler: bath temperature: 50 DEG C
Quantitative loop temperature: 180 DEG C
Transfer conduit temperature: 180 DEG C
Sample injection bottle equilibration time: 25min
(2) specificity test, linear and scope test, the test of system reappearance, detectability test, quantitative limit test, recovery test, analysis reappearance are tested, in albendazole bulk drug formic acid residue detection with embodiment 1.
Embodiment 3
1, condition determination and parameter:
The capillary column (varian CP-SIL5CB50m × 0.32mm × 5 μm) of gas chromatograph.
Carrier gas: nitrogen, constant voltage: 125kPa, the bypass flow of injector: 30ml/min, the temperature of injector: 200 DEG C, detecting device: hydrogen flame ion detector (FID), detector temperature: 300 DEG C, hydrogen: 25ml/min, air: 400ml/min
Column temperature: temperature programme (programmed analysis)
| Initial temperature | 40℃ |
| The initial temperature retention time | 0.5min |
| Heating rate 1 | 10℃/min |
| Finishing temperature 1 | 75℃ |
| Temperature hold-time 1 | 5min |
| Heating rate 2 | 50℃/min |
| Finishing temperature 2 | 250℃ |
| Temperature hold-time 2 | 10min |
Head-space sampler: bath temperature: 60 DEG C
Quantitative loop temperature: 220 DEG C
Transfer conduit temperature: 220 DEG C
Sample injection bottle equilibration time: 25min
(2) specificity test, linear and scope test, the test of system reappearance, detectability test, quantitative limit test, recovery test, analysis reappearance are tested, in Flubendazole bulk drug formic acid residue detection with embodiment 1.
Embodiment 4
1, condition determination and parameter:
The capillary column (Agilent DB624(25m × 0.25mm × 2.55um) of gas chromatograph.
Carrier gas: nitrogen, constant voltage: 125kPa, the bypass flow of injector: 30ml/min, the temperature of injector: 200 DEG C, detecting device: hydrogen flame ion detector (FID), detector temperature: 300 DEG C, hydrogen: 25ml/min, air: 400ml/min
Column temperature: temperature programme (programmed analysis)
| Initial temperature | 40℃ |
| The initial temperature retention time | 0.5min |
| Heating rate 1 | 8℃/min |
| Finishing temperature 1 | 75℃ |
| Temperature hold-time 1 | 0min |
| Heating rate 2 | 40℃/min |
| Finishing temperature 2 | 230℃ |
| Temperature hold-time 2 | 8.3min |
Head-space sampler: bath temperature: 80 DEG C
Quantitative loop temperature: 250 DEG C
Transfer conduit temperature: 250 DEG C
Sample injection bottle equilibration time: 30min
(2) specificity test, linear and scope test, the test of system reappearance, detectability test, quantitative limit test, recovery test, analysis reappearance are tested, in mebendazole bulk drug formic acid residue detection with embodiment 1.
The invention is not restricted to above-described embodiment, all any simple, equivalent variations of doing above-described embodiment according to technical spirit of the present invention or modification, all belong within the scope of the technology of the present invention.
Claims (4)
1., for detecting the method that in Anthelmintic imidazoles, formic acid is residual, it is characterized in that, this detection method comprises the following steps:
(1) solution preparation: described solution preparation comprises the steps:
The dimethyl sulfoxide solution of A, preparation 2.5% (v/v) sulfuric acid is dilute solution;
B, precision take Anthelmintic imidazoles sample 200.0mg and enter 20ml headspace sampling bottle, add 0.1ml methyl alcohol, then pipette 2ml dilute solution and make test liquid;
C, pipette 10ul formic acid in 50ml volumetric flask, be diluted to scale with dilute solution, shake up the standard reserving solution being mixed with 2000ppm;
D, in 50ml volumetric flask, add 20ml dilute solution, precision pipettes 25ml standard reserving solution, and dilute solution is settled to scale, accurately pipettes 2ml and enters 20ml headspace sampling bottle, then add 0.1ml methyl alcohol, make reference substance solution;
(2) vapor detection: described vapor detection comprises the steps:
A, get reference substance solution and carry out gas Chromatographic Determination, record chromatogram, get the formic acid duplicate measurements of variable concentrations for several times, record chromatographic peak area, draws the peak area of methyl formate and the graph of a relation of formic acid concn,
To go forward side by side line linearity matching, obtain linear equation Y=a X+b
A-slope
B-intercept
Peak area in Y-contrast liquid after methyl formate correction
The concentration (ppm, sample marker amount is 200mg) of formic acid in X-contrast liquid;
B, according to steps A, reappearance is carried out to formic acid reference substance solution;
C, according to steps A, need testing solution to be detected, by the peak area value after correcting by formic acid concn X in following formulae discovery test sample;
The concentration (ppm) of target solvent in X-sample
The corrected value of target solvent peak area in Y-test liquid
The sample weighting amount (mg) of sample in Wa-test liquid
200.0-sample marker amount (mg);
Testing conditions and the parameter of described detection method are as follows: carrier gas: nitrogen, constant voltage: 95 ~ 120kPa, injector: bypass flow 15 ~ 20ml/min, temperature 200 ~ 250 DEG C, detecting device: hydrogen flame ion detector, detector temperature: 290 ~ 300 DEG C, head-space sampler bath temperature: 50 ~ 60 DEG C, head-space sampler quantitative loop temperature: 180 ~ 220 DEG C, head-space sampler transfer conduit temperature: 180 ~ 220 DEG C, head-space sampler sample injection bottle equilibration time: 15 ~ 25min;
In described vapor detection, the temperature of detecting device adopts programmed temperature method, the initial temperature of described programmed temperature method is 40 DEG C, heating rate 1 is 5 ~ 10 DEG C/min, finishing temperature 1 is 75 DEG C, keep the follow-up temperature of continuing rising of 0 ~ 5min, heating rate 2 is 30 ~ 50 DEG C/min, and finishing temperature 2 is 180 ~ 250 DEG C, and temperature hold-time 2 is 8 ~ 10min.
2. the detection method that in a kind of Anthelmintic imidazoles according to claim 1, formic acid solvent is residual, is characterized in that: the detection of described formic acid is limited to 5-15ppm.
3. the detection method that in a kind of Anthelmintic imidazoles according to claim 1, formic acid solvent is residual, is characterized in that: described formic acid be quantitatively limited to 10-30ppm.
4. the detection method that in a kind of Anthelmintic imidazoles according to claim 1, formic acid solvent is residual, it is characterized in that, described imidazoles comprises: albendazole, mebendazole, Flubendazole, Fenbendazole, oxfendazole, Oxibendazole, Luxabendazole, thiabendazole.
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| CN110514763A (en) * | 2019-09-03 | 2019-11-29 | 山东省药学科学院 | A kind of high-efficiency liquid chromatography method for detecting directly measuring Analysis of Formic acid Residual in methyl formate |
| CN111595984B (en) * | 2020-07-08 | 2022-07-12 | 山西省食品药品检验所(山西省药品包装材料监测中心) | Method for detecting formic acid in ant product |
| CN112034075A (en) * | 2020-10-13 | 2020-12-04 | 湖北省宏源药业科技股份有限公司 | Method for checking limit of residual methyl formate and methanol in metronidazole |
| CN115754083A (en) * | 2022-11-29 | 2023-03-07 | 广西电网有限责任公司电力科学研究院 | Method for testing methyl formate in insulating oil |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU1331262A1 (en) * | 1984-12-07 | 1995-12-27 | М.К. Старчевский | Gas chromatography method for detecting formic acid |
| CN102901784A (en) * | 2012-11-02 | 2013-01-30 | 江苏吉贝尔药业有限公司 | Method for performing headspace gas chromatographic detection on formic acid in aceclofenac bulk pharmaceutical chemicals |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012040318A2 (en) * | 2010-09-23 | 2012-03-29 | University Of Miami | Compositions, methods and kits for detecting melanoma and margins of melanoma |
-
2013
- 2013-12-05 CN CN201310653659.2A patent/CN103630628B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU1331262A1 (en) * | 1984-12-07 | 1995-12-27 | М.К. Старчевский | Gas chromatography method for detecting formic acid |
| CN102901784A (en) * | 2012-11-02 | 2013-01-30 | 江苏吉贝尔药业有限公司 | Method for performing headspace gas chromatographic detection on formic acid in aceclofenac bulk pharmaceutical chemicals |
Non-Patent Citations (2)
| Title |
|---|
| Gas chromatographic Head-space assay of formic acid as methyl formate in biologic fluids:Potential application to methanol poisoning;Craig abolin et al.;《BIOCHEMICAL MEDICINE》;19801231;第23卷;全文 * |
| 柱前衍生化顶空气相色谱法同时检测非布司他原料药中3中微量有机酸;朱圣亮等;《中国药房》;20121231;第23卷(第25期);第2373页第2.1-2.2、2.5-2.6和2.8部分 * |
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| CN103630628A (en) | 2014-03-12 |
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