CN103543231B - The method for separating and analyzing of chloroform residual quantity in a kind of meclozine hydrochloride - Google Patents
The method for separating and analyzing of chloroform residual quantity in a kind of meclozine hydrochloride Download PDFInfo
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Abstract
The invention discloses the method for separating and analyzing of chloroform residual quantity in a kind of meclozine hydrochloride.The method adopts gas chromatography (GC) method, electron capture detector (ECD) carrys out the residual quantity of chloroform in compartment analysis meclozine hydrochloride, the shortcoming that when vapor-phase chromatography the method overcoming traditional flame ionization ditector (FID) detects, chloroform response is low.In the method, the response of chloroform is high, highly sensitive, easy and simple to handle, in other bulk drug, the foundation of chloroform residual quantity quality standard provides Technical Reference.
Description
Technical field
The present invention relates to a kind of method for separating and analyzing of sample.Particularly relate to the method for separating and analyzing of chloroform residual quantity in a kind of meclozine hydrochloride.
Background technology
The chemical name of meclozine hydrochloride is 1-[(4-chlorphenyl) benzyl]-4-[(3-tolyl) methyl]-piperazine dihydrochloride; English name is 1-[(4-Chlorophenyl)-phenylmethyl]-4-[(3-methylphenyl) methyl] piperazine dihydrochloride; Molecular formula is C
25h
27clN
22HCl; Molecular weight is 463.88; Chemical structural formula is as shown in the formula shown in I:
Meclozine hydrochloride is the medicine that Chinese Pharmacopoeia (version in 2010) records, No. CAS: 1104-22-9, and be the antagonist of histamine receptor, be applicable to various mucocutaneous anaphylactic disease, also can be used for the Nausea and vomiting that gestation, radiotherapy and motion sickness cause.Its effect is lasting far beyond diphenhydramine, can maintain 12 ~ 24 hours.The residual solvent item used in this kind building-up process is not investigated in Chinese Pharmacopoeia version in 2010.Meclozine hydrochloride synthesis technique is as follows:
Chloroform equal solvent has been used during synthesis, according to the classification in International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human use view and ICH (International Conference on Harmonization OF TechnicalRequirements for Registration of Pharmaceuticals for Human Use), chloroform is two kind solvents.In order to strictly control drug quality, ensureing the safe and effective of its clinical application, should check the residual quantity of chloroform in meclozine hydrochloride.Once used flame ionization ditector (FID) method to detect chloroform in other medicinal compounds, but the present inventor tests and finds to adopt flame ionization ditector (FID), chloroform response is too low, cannot the residual quantity of chloroform in Accurate Determining sample.The shortcoming that when vapor-phase chromatography that the method that the present inventor sets up overcomes traditional flame ionization ditector (FID) detects, chloroform response is low, the response of newly-established method chloroform is high, highly sensitive, easy and simple to handle, accurately can detect the residual quantity of chloroform in meclozine hydrochloride.
Summary of the invention
The object of the present invention is to provide the method for separating and analyzing of chloroform residual quantity in a kind of meclozine hydrochloride.The method adopts gas chromatography (GC) method, and electron capture detector (ECD) detects the residual quantity of chloroform in meclozine hydrochloride.
Method of the present invention compared with prior art has the following advantages and good effect:
The shortcoming that when vapor-phase chromatography that method of the present invention overcomes traditional flame ionization ditector (FID) detects, chloroform response is low.In the method, the response of chloroform is high, highly sensitive, easy and simple to handle, in other bulk drug, the foundation of chloroform residual quantity quality standard provides Technical Reference.
The present invention is specially:
A method for separating and analyzing for chloroform residual quantity in meclozine hydrochloride, comprising:
1), chromatographic condition:
Gas chromatograph, electron capture detector;
The temperature of electron capture detector is 200 DEG C ~ 300 DEG C; Injector temperature 170 DEG C ~ 275 DEG C;
Gas chromatograph chromatographic column used is capillary gas chromatographic column; Described capillary gas chromatographic column is nonpolar, low pole or middle polarity chromatographic column;
The column temperature of described capillary gas chromatographic column is 40 DEG C ~ 60 DEG C, described column temperature maintains 8 minutes ~ 30 minutes, described chromatographic condition also comprises working procedure after a chromatographic column, after described chromatographic column, working procedure is for be set to 180 DEG C ~ 220 DEG C by column temperature, and after described chromatographic column, working procedure column temperature maintains 5 minutes ~ 30 minutes;
Carrier gas is nitrogen or helium, flow rate of carrier gas: 1ml/min ~ 10ml/min.
2), the preparation of need testing solution:
Get meclozine hydrochloride 0.05g ~ 0.3g, accurately weighed, in top set empty bottle, precision adds about 1ml ~ 6ml solvent, as need testing solution.Described solvent is methyl alcohol, ethanol, isopropyl alcohol, the tert-butyl alcohol, cyclohexane, heptane, DMF or dimethyl sulfoxide (DMSO).
3), the preparation of reference substance solution:
Get chloroform appropriate, accurately weighed, make the solution of every 1ml containing chloroform 0.001mg ~ 0.012mg with solvent dilution, precision measures 1ml ~ 6ml and puts in advance precision weighing and add in the ml headspace bottle of 0.05g ~ 0.3g meclozine hydrochloride sample, product solution in contrast.
4), measure:
Get need testing solution and reference substance solution, headspace sampling, head space equilibration time 20 ~ 60 minutes; Record chromatogram.
Preferably, step 2) and 3) described in solvent be methyl alcohol, ethanol, isopropyl alcohol, DMF, dimethyl sulfoxide (DMSO).Particular methanol, ethanol, isopropyl alcohol.Most preferably methyl alcohol.
Preferably, described column temperature is 45 DEG C; Described column temperature maintains 15 minutes.
Preferably, described rear operation column temperature 200 DEG C, described rear operation column temperature maintains 5 minutes.
Preferably, described head space equilibration time is 30 minutes.
Preferably, described injector temperature is 250 DEG C.
Preferably, described detector temperature is 300 DEG C.
Preferably, described flow rate of carrier gas is 3ml/min.
Need testing solution preparation method of the present invention can also be for: step 2) described in the preparation method of need testing solution can also for dissolve test sample with inner mark solution, ethanol, isopropyl alcohol, the tert-butyl alcohol, cyclohexane, heptane is designated as in described, and different from described test sample solvent; The compound method of described inner mark solution is: get interior mark and add step 2) in test sample solvent be mixed with the solution of 0.05mg/ml ~ 0.5mg/ml.Preferably get interior mark and add step 2) in test sample solvent be mixed with the solution of 0.1mg/ml.When test sample solvent is methyl alcohol, interior mark is preferably ethanol.
Reference substance solution preparation method of the present invention can also be for: the preparation method of the reference substance solution described in step 3) can also for dissolve chloroform with inner mark solution, ethanol, isopropyl alcohol, the tert-butyl alcohol, cyclohexane, heptane is designated as in described, and different from described test sample solvent; The compound method of described inner mark solution is: get interior mark and add step 2) in test sample solvent be mixed with the solution of 0.05mg/ml ~ 0.5mg/ml.Preferably get interior mark and add step 2) in test sample solvent be mixed with the solution of 0.1mg/ml.When test sample solvent is methyl alcohol, interior mark is preferably ethanol.
Preferably, the capillary chromatographic column that the capillary chromatographic column of described nonpolar, low pole and middle polarity is is Stationary liquid with following material: dimethyl polysiloxane, 5%-diphenyl-95%-dimethyl polysiloxane, 6%-cyanogen propylbenzene-94%-dimethyl polysiloxane, 35%-diphenyl-65%-dimethyl polysiloxane or 14%-cyanogen propylbenzene-86%-dimethyl polysiloxane.Preferably with the capillary chromatographic column that 6%-cyanogen propylbenzene-94%-dimethyl polysiloxane is Stationary liquid.
Preferably, described capillary chromatographic column is middle polarity chromatographic column.
Method for separating and analyzing of the present invention is preferably:
1), chromatographic condition:
Gas chromatograph, electron capture detector;
The temperature of electron capture detector is 300 DEG C; Injector temperature 250 DEG C;
Gas chromatograph chromatographic column used is capillary gas chromatographic column; Described capillary gas chromatographic column is 6% cyanogen propylbenzene-94% dimethyl polysiloxane multipolymer is the capillary column of Stationary liquid;
The column temperature of described capillary gas chromatographic column is 45 DEG C, and described column temperature maintains 15 minutes;
Described chromatographic condition also comprises working procedure after a chromatographic column, and after described chromatographic column, working procedure is for be set to 200 DEG C by column temperature, and after described chromatographic column, working procedure column temperature maintains 5 minutes;
Carrier gas is nitrogen or helium, flow rate of carrier gas: 1ml/min ~ 10ml/min.
2), the preparation of need testing solution:
Get meclozine hydrochloride 0.05g ~ 0.3g, accurately weighed, in top set empty bottle, precision adds about 1ml ~ 6ml solvent, as need testing solution.Described solvent is methyl alcohol, ethanol, isopropyl alcohol, the tert-butyl alcohol, cyclohexane, heptane, DMF or dimethyl sulfoxide (DMSO).
3), the preparation of reference substance solution:
Get chloroform appropriate, accurately weighed, make the solution of every 1ml containing chloroform 0.001mg ~ 0.012mg with solvent dilution, precision measures 1ml ~ 6ml and puts in advance precision weighing and add in the ml headspace bottle of 0.05g ~ 0.3g meclozine hydrochloride sample, product solution in contrast.
4), measure:
Get need testing solution and reference substance solution, headspace sampling, head space equilibration time 20 ~ 60 minutes; Record chromatogram.
The most preferred scheme of method for separating and analyzing of the present invention is:
1), chromatographic condition:
Gas chromatograph, electron capture detector;
The temperature of electron capture detector is 300 DEG C; Injector temperature 250 DEG C;
Gas chromatograph chromatographic column used is capillary gas chromatographic column; Described capillary gas chromatographic column is 6% cyanogen propylbenzene-94% dimethyl polysiloxane multipolymer is the capillary column of Stationary liquid;
The column temperature of described capillary gas chromatographic column is 45 DEG C, described column temperature maintains 15 minutes, described chromatographic condition also comprises working procedure after a chromatographic column, and after described chromatographic column, working procedure is for be set to 200 DEG C by column temperature, and after described chromatographic column, working procedure column temperature maintains 5 minutes;
Carrier gas is nitrogen, flow rate of carrier gas: 3ml/min.
2), the preparation of need testing solution:
Get meclozine hydrochloride 0.1g, accurately weighed, in top set empty bottle, precision adds about 2ml methyl alcohol, as need testing solution;
3), the preparation of reference substance solution:
Get chloroform reference substance, accurately weighed, make every 1ml containing the solution of chloroform 0.003mg with methanol dilution, precision measures 2ml and puts in advance precision weighing and add in the ml headspace bottle of 0.1g meclozine hydrochloride sample, product solution in contrast;
4), measure:
Get need testing solution and reference substance solution, headspace sampling, head space equilibration time 30 minutes; Record chromatogram.
Chloroform in meclozine hydrochloride of the present invention is present in all kinds of formulations of tablet, injection or injection.
Solvent of the present invention comprises methyl alcohol, ethanol, isopropyl alcohol, the tert-butyl alcohol, heptane, DMF, dimethyl sulfoxide (DMSO).Above-mentioned solvent can both effectively be separated with chloroform, does not disturb the detection of chloroform.Therefore above-mentioned solvent can as the solvent detecting chloroform residual quantity in meclozine hydrochloride.Make solvent with methyl alcohol, chromatographic peak retention time is short, and analysis time used is more moderate, therefore particular methanol, the chromatogram of methyl alcohol location is shown in Fig. 1, and the chromatogram of chloroform location is shown in Fig. 2.
The capillary chromatographic column of nonpolar, low pole of the present invention and middle polarity comprises the capillary chromatographic column that Stationary liquid is respectively following material: dimethyl polysiloxane, (5%)-diphenyl-(95%)-dimethyl polysiloxane, (6%)-cyanogen propylbenzene-(94%)-dimethyl polysiloxane, (35%)-diphenyl-(65%)-dimethyl polysiloxane, (14%)-cyanogen propylbenzene-(86%)-dimethyl polysiloxane.These chromatographic columns can be used for the separation of chloroform in meclozine hydrochloride.Wherein Stationary liquid is that the chromatographic column of (6%)-cyanogen propylbenzene-(94%)-dimethyl polysiloxane is comparatively conventional, and polarity is moderate, chloroform chromatogram peak-to-peak type is better, therefore preferably Stationary liquid is the capillary chromatographic column of (6%)-cyanogen propylbenzene-(94%)-dimethyl polysiloxane.
The determination method of chloroform residual quantity: for peak area, calculates the residual quantity of chloroform by standard addition method.
Technical scheme of the present invention compared with prior art has the following advantages:
1, electron capture detector (ECD)
Adopt ECD detecting device to detect chloroform, overcome the shortcoming that when adopting traditional flame ionization ditector (FID) to detect, chloroform response is low.In the method, the response of chloroform is high, highly sensitive.
2, chromatographic column column temperature
By the screening of chromatographic column column temperature condition, can draw, when chromatogram column temperature is 100 DEG C, 80 DEG C, it is too fast that chloroform goes out peak, and during solvent baseline lack of equilibrium, chloroform just goes out peak, and the hangover of chloroform peak type, affects the accurate calculating of chloroform residual quantity.And chromatogram column temperature is when being 60 DEG C, 45 DEG C, 40 DEG C, baseline is comparatively steady, and chloroform chromatogram peak-to-peak type is more symmetrical, and the retention time of solvent peak and chloroform is more moderate, accurately can calculate the residual quantity of chloroform.I.e. chromatographic column column temperature preferably 40 DEG C ~ 60 DEG C, maintains 15 minutes by more preferably 45 DEG C.
3, working procedure after chromatographic column column temperature
By chromatographic column column temperature is taked temperature programme, etc. degree do not establish rear working procedure, etc. degree the comparative study of rear working procedure is set, when finding that chromatographic column takes degree such as grades not arrange rear working procedure, baseline not steadily, cannot Accurate Determining chloroform content; When chromatogram column temperature takes temperature programme, baseline is difficult to get back to equilibrium position, and chloroform chromatographic peak type is asymmetric, cannot Accurate Determining chloroform content; When chromatogram column temperature takes degree such as grade to arrange rear working procedure, baseline is comparatively steady, and chloroform chromatogram peak-to-peak type is symmetrical, can Accurate Determining chloroform content.The i.e. preferred column temperature of chromatogram column temperature 40 DEG C ~ 60 DEG C, maintains 8 minutes ~ 30 minutes, and rear operation column temperature 180 DEG C ~ 220 DEG C maintains 5 minutes ~ 30 minutes; More preferably column temperature 45 DEG C, maintains 15 minutes, rear operation 200 DEG C, maintains 5 minutes.
4, chloroform determination of residual amount method-standard addition method
Verify discovery by experiment, when adopting external standard method, owing to there is the interference of matrix effect, can not Accurate Determining chloroform residual quantity; Adopt standard addition method, can eliminate matrix effect, effect is better, can Accurate Determining chloroform residual quantity.
5, head space equilibration time
By the screening to head space equilibration time, learn, head space balance 10 minutes, 15 minutes time, chloroform gas volatilization not exclusively, can not Accurate Determining chloroform residual quantity; When head space balances 20 minutes ~ 60 minutes, chloroform gas volatilization completely, can the residual quantity of Accurate Determining chloroform.Preferred head space balances 30 minutes.
Accompanying drawing explanation
Fig. 1: solvent methanol location GC chromatogram;
Fig. 2: chloroform location GC chromatogram;
Fig. 3: condition 1 time chloroform reference substance GC chromatogram;
Fig. 4: condition 5 times chloroform reference substance GC chromatograms;
Fig. 5: condition 6 times chloroform reference substance GC chromatograms;
Fig. 6: chloroform minimum detectability GC chromatogram;
Fig. 7: the minimum quantitative limit GC chromatogram of chloroform;
Fig. 8: sample introduction precision test chloroform GC chromatogram;
Fig. 9: replica test contrast solution GC chromatogram;
Figure 10: replica test need testing solution GC chromatogram;
Figure 11: recovery test need testing solution GC chromatogram;
Figure 12: recovery test contrast solution GC chromatogram;
Figure 13: recovery test 80% recovery sample solution GC chromatogram;
Figure 14: recovery test 100% recovery sample solution GC chromatogram;
Figure 15: recovery test 120% recovery sample solution GC chromatogram;
Figure 16: embodiment 1 reference substance GC chromatogram;
Figure 17: embodiment 1 sample GC chromatogram;
Figure 18: embodiment 3 sample GC chromatogram;
Figure 19: embodiment 4 sample GC chromatogram;
Figure 20: embodiment 5 sample GC chromatogram;
Figure 21: embodiment 6 sample GC chromatogram;
Figure 22: embodiment 7 sample GC chromatogram;
Figure 23: embodiment 8 sample GC chromatogram;
Figure 24: embodiment 9 sample GC chromatogram.
Embodiment
Below by way of embodiment and the invention will be further described with reference to the description of accompanying drawing, but this is not limitation of the present invention, those skilled in the art are according to basic thought of the present invention, various amendment or improvement can be made, but only otherwise depart from basic thought of the present invention, all within the scope of the present invention.
Experimental example 1:
Experiment name: chloroform determination of residual amount optimize chromatography condition in meclozine hydrochloride
Experiment purpose: chloroform determination of residual amount method in meclozine hydrochloride, is optimized chromatogram column temperature condition
Experimental technique: Agilent 7820A gas chromatograph, Agilent 7694E head-space sampler.Employing (6%) cyanogen propylbenzene-(94%) dimethyl polysiloxane multipolymer is the capillary column (30m × 0.53mm × 3.0 μm) of Stationary liquid, adopt electron capture detector (ECD), detector temperature 300 DEG C, injector temperature 250 DEG C, carrier gas nitrogen, flow rate of carrier gas is 3ml per minute;
Chromatogram column temperature: adopt 100 DEG C, 80 DEG C, 60 DEG C, 45 DEG C respectively, maintains 6-15 minute;
Rear operation 200 DEG C, maintains 5 minutes; Or rear working procedure is not set;
Head space equilibration time 10,15,30,60 minutes;
Get chloroform reference substance appropriate, make every 1ml about containing the solution of chloroform 0.003mg with methanol dilution, precision measures 2ml and puts in advance precision weighing and add meclozine hydrochloride sample and be about in the ml headspace bottle of 0.1g,
Experimental result: in table 1
In meclozine hydrochloride in chloroform determination of residual amount method, the present inventor is optimized chromatogram column temperature condition, has carried out comparative study to the need of rear operation, has carried out the comparative studies of head space equilibration time simultaneously.The results are shown in Table 1, the chromatogram of the chloroform under chromatographic condition 1 is shown in Fig. 3; The chromatogram of the chloroform under chromatographic condition 5 is shown in Fig. 4.The chromatogram of the chloroform under chromatographic condition 6 is shown in Fig. 5.
Table 1: chromatographic column column temperature and head space equilibration time optimum results
Experiment conclusion:
Known by experiment, condition 1,2,3 undesirable, condition 4,5,6,7 all meets the requirements.
By the screening of above-mentioned chromatogram column temperature condition, during chromatogram column temperature 40-60 DEG C, chromatogram peak-to-peak type is better, and baseline is more steady.Optimum when 45 DEG C.
After adding rear working procedure, contribute to baseline steady, chloroform peak type is better.Run 200 DEG C preferably, keep the condition of 5 minutes.
Head space equilibration time 30-60 minute meets the requirements, preferably balance 30 minutes.
Chloroform residue checking in meclozine hydrochloride: highly sensitive by the method validation such as linear test, sample introduction precision test, replica test, minimum detectability and the test of minimum quantitative limit, recovery test test proof the method for the invention, accuracy good, can go out the residual quantity of chloroform in meclozine hydrochloride by Accurate Determining.
Experimental example 2:
Experiment name: chloroform residue checking-linear test in meclozine hydrochloride
Experiment purpose: by the range of linearity of chloroform residue in linear test checking meclozine hydrochloride
Experimental technique: Agilent 7820A gas chromatograph, Agilent 7694E head-space sampler.Employing (6%) cyanogen propylbenzene-(94%) dimethyl polysiloxane multipolymer is the capillary column (30m × 0.53mm × 3.0 μm) of Stationary liquid, adopt electron capture detector (ECD), detector temperature 300 DEG C, injector temperature 250 DEG C, carrier gas nitrogen, flow rate of carrier gas is 3ml per minute; Chromatogram column temperature: 45 DEG C maintain 15 minutes, and rear operation 200 DEG C, maintains 5 minutes; Head space equilibration time 30 minutes.
Get chloroform and be about 16.5mg, accurately weighed, put in 25ml measuring bottle, with methanol dilution to scale, shake up, as strong solution.Precision measures strong solution in right amount respectively, becomes concentration to be respectively the solution of 0.66 μ g/ml, 1.65 μ g/ml, 3.3 μ g/ml, 6.6 μ g/ml, 16.5 μ g/ml, shake up with methanol dilution.Precision measures headspace sampling in the solution 2ml top set empty bottle of each concentration respectively, and record chromatogram, does linear regression with concentration and peak area.
Experimental result: chloroform linear test result is as table 2.
Table 2: meclozine hydrochloride chloroform determination of residual amount linear test result
Experiment conclusion: the concentration range of the chloroform reference substance described in claim 1 of the present invention is 1 μ g/ml ~ 12 μ g/ml, above-mentioned experiment proves that chloroform is within the scope of 0.66 μ g/ml ~ 16.5 μ g/ml, and linear relationship is good.
Experimental example 3:
Experiment name: chloroform residue checking-minimum detectability and minimum quantitative limit in meclozine hydrochloride
Experiment purpose: by the sensitivity of chloroform residue in minimum detectability and minimum quantitative limit checking meclozine hydrochloride.
Experimental technique: Agilent 7820A gas chromatograph, Agilent 7694E head-space sampler.Employing (6%) cyanogen propylbenzene-(94%) dimethyl polysiloxane multipolymer is the capillary column (30m × 0.53mm × 3.0 μm) of Stationary liquid, adopt electron capture detector (ECD), detector temperature 300 DEG C, injector temperature 250 DEG C, carrier gas nitrogen, flow rate of carrier gas is 3ml per minute; Chromatogram column temperature: 45 DEG C maintain 15 minutes, and rear operation 200 DEG C, maintains 5 minutes; Head space equilibration time 30 minutes.
Get the solution of 0.66 μ g/ml in chloroform linear test, use methyl alcohol stepwise dilution, measure minimum detectability and minimum quantitative limit.
Experimental result:
In 3 of noise times, the concentration limit recording chloroform is 4.95ng/ml.
In 10 of noise times, recording minimum quantitative concentrations is 13.2ng/ml.Chromatogram is shown in Fig. 6 ~ 7.
Experiment conclusion: the detection limit of the method chloroform reaches nanogram level, and method is enough sensitive.
Experimental example 4:
Experiment name: chloroform residue checking-Precision Experiment in meclozine hydrochloride
Experiment purpose: by the precision of chloroform residue in precision checking meclozine hydrochloride
Experimental technique: Agilent 7820A gas chromatograph, Agilent 7694E head-space sampler.Employing (6%) cyanogen propylbenzene-(94%) dimethyl polysiloxane multipolymer is the capillary column (30m × 0.53mm × 3.0 μm) of Stationary liquid, adopt electron capture detector (ECD), detector temperature 300 DEG C, injector temperature 250 DEG C, carrier gas nitrogen, flow rate of carrier gas is 3ml per minute; Chromatogram column temperature: 45 DEG C maintain 15 minutes, and rear operation 200 DEG C, maintains 5 minutes; Head space equilibration time 30 minutes;
Get the solution of 3.3 μ g/ml in chloroform linear test, precision measures 2ml, in top set empty bottle, and parallel preparation 6 parts, headspace sampling, record chromatogram.Calculate the RSD% of peak area, chromatogram is shown in Fig. 8.
Experimental result: the results are shown in Table 3.
Table 3: meclozine hydrochloride chloroform determination of residual amount sample introduction Precision test result
| Sample | Peak area |
| 1 | 10192.3 |
| 2 | 10213.6 |
| 3 | 10187.9 |
| 4 | 9934.48 |
| 5 | 10424.9 |
| 6 | 9994.79 |
| RSD% | 1.72 |
Experiment conclusion: continuous sample introduction 6 times, the RSD% of peak area is less than 2%, and sample introduction precision is good.
Experimental example 5:
Experiment name: chloroform residue checking-repeated experiment in meclozine hydrochloride
Experiment purpose: by the repeatability of chloroform residue in repeated experiment checking meclozine hydrochloride
Experimental technique: Agilent7820A gas chromatograph, Agilent7694E head-space sampler.Employing (6%) cyanogen propylbenzene-(94%) dimethyl polysiloxane multipolymer is the capillary column (30m × 0.53mm × 3.0 μm) of Stationary liquid, adopt electron capture detector (ECD), detector temperature 300 DEG C, injector temperature 250 DEG C, carrier gas nitrogen, flow rate of carrier gas is 3ml per minute; Chromatogram column temperature: 45 DEG C maintain 15 minutes, and rear operation 200 DEG C, maintains 5 minutes; Head space equilibration time 30 minutes, headspace sampling.
Get this product and be about 0.1g, accurately weighed, in top set empty bottle, precision adds methyl alcohol 2ml, as need testing solution; It is appropriate that another precision takes chloroform reference substance, makes every 1ml about containing the solution of chloroform 0.003mg with methanol dilution, and precision measures 2ml and puts in advance precision weighing and add meclozine hydrochloride sample and be about in the ml headspace bottle of 0.1g, product solution in contrast.Get need testing solution and reference substance solution.
Prepare two parts of reference substance solution and six parts of need testing solutions respectively, measure the residual quantity of chloroform in six parts of test samples, chromatogram is shown in Fig. 9 ~ 10.
Experimental result: chloroform measurement result is in table 4.
Table 4: meclozine hydrochloride chloroform determination of residual amount replica test result
| Sample | Peak area | Chloroform residual quantity % |
| 1 | 23.005 | 0.00002 |
| 2 | 22.886 | 0.00002 |
| 3 | 38.646 | 0.00003 |
| 4 | 26.649 | 0.00002 |
| 5 | 25.127 | 0.00002 |
| 6 | 25.617 | 0.00002 |
Experiment conclusion: in six increment product, the measurement result of chloroform residual quantity is basically identical, repeatability better.
Experimental example 6:
Experiment name: chloroform residue checking-recovery experiment in meclozine hydrochloride
Experiment purpose: by the accuracy of chloroform residue in recovery experimental verification meclozine hydrochloride
Experimental technique: Agilent 7820A gas chromatograph, Agilent 7694E head-space sampler.Employing (6%) cyanogen propylbenzene-(94%) dimethyl polysiloxane multipolymer is the capillary column (30m × 0.53mm × 3.0 μm) of Stationary liquid, adopt electron capture detector (ECD), detector temperature 300 DEG C, injector temperature 250 DEG C, carrier gas nitrogen, flow rate of carrier gas is 3ml per minute; Chromatogram column temperature: 45 DEG C maintain 15 minutes, and rear operation 200 DEG C, maintains 5 minutes; Head space equilibration time 30 minutes, headspace sampling.
(1), the preparation of need testing solution: get this product and be about 0.1g, accurately weighed, in top set empty bottle, precision adds methyl alcohol 2ml, as need testing solution, measures its residual quantity;
(2), the preparation of reference substance solution: get chloroform and be about 15mg, accurately weighed, put in 25ml measuring bottle, with methanol dilution to scale, shake up, as stock solution; Precision measures storing solution 0.25ml and puts in 50ml measuring bottle, with methanol dilution to scale, shakes up, in contrast solution, and precision measures the molten sample 2ml of contrast and puts in advance precision weighing and add meclozine hydrochloride sample and be about in the ml headspace bottle of 0.1g, product solution in contrast;
(3), the preparation of recovery sample solution:
Precision measures stock solution 0.20ml, 0.25ml, 0.30ml, put in 50ml measuring bottle respectively, with methanol dilution to scale, shake up, as 80%, 100%, 120% contrast solution, the accurate 2ml that measures puts in advance precision weighing and adds meclozine hydrochloride sample and be about in the ml headspace bottle bottle of 0.1g respectively, and each parallel preparation 3 parts, as recovery sample solution;
Get need testing solution, reference substance solution and recovery sample solution, headspace sampling, record chromatogram, calculates the recovery of chloroform by standard addition method.Chromatogram is shown in Figure 11 ~ 15.
Experimental result: chloroform recovery test the results are shown in Table 5:
Table 5: meclozine hydrochloride chloroform determination of residual amount recovery test result
Experiment conclusion: the recovery of high, medium and low 3 kinds of concentration 9 increment product is all between 95 ~ 105%, and RSD is all less than 4.0%, and illustration method accuracy meets the requirements.
Mode by the following examples further explains and describes content of the present invention, but these embodiments are not to be construed as limiting the scope of the invention.
Embodiment 1:
(1), chromatographic condition
Instrument: Agilent 7820A gas chromatograph, Agilent 7694E head-space sampler.Stationary liquid is the capillary gas chromatographic column of (6%)-cyanogen propylbenzene-(94%)-dimethyl polysiloxane; Detecting device is electron capture detector (ECD), detector temperature 300 DEG C; Injector temperature 250 DEG C; Column temperature 45 DEG C, maintains 15 minutes, rear operation 200 DEG C, maintains 5 minutes.Carrier gas is nitrogen, flow rate of carrier gas: 3ml/min.Headspace sampling, head space equilibration time 30 minutes.
(2), sample thief is about 0.1g, and accurately weighed, in top set empty bottle, precision adds methyl alcohol 2ml, as need testing solution; It is appropriate that another precision takes chloroform reference substance, makes every 1ml about containing the solution of chloroform 0.003mg with methanol dilution, and precision measures 2ml and puts in advance precision weighing and add meclozine hydrochloride sample and be about in the ml headspace bottle of 0.1g, product solution in contrast.
(3), need testing solution and reference substance solution is got, headspace sampling, record chromatogram.By standard addition method, with the residual quantity of calculated by peak area chloroform.
Under this condition, methyl alcohol and chloroform can baseline separation, and chloroform chromatogram peak-to-peak type is better, and baseline is comparatively steady, can the residual quantity of Accurate Determining chloroform.Chromatogram is shown in Figure 16 ~ 17.
Embodiment 2:
(1), chromatographic condition
Instrument: Agilent 7820A gas chromatograph, Agilent 7694E head-space sampler.Stationary liquid is the capillary gas chromatographic column of (6%)-cyanogen propylbenzene-(94%)-dimethyl polysiloxane; Detecting device is electron capture detector (ECD), detector temperature 300 DEG C; Injector temperature 250 DEG C; Column temperature 45 DEG C, maintains 15 minutes, rear operation 200 DEG C, maintains 5 minutes.Carrier gas is nitrogen, flow rate of carrier gas: 3ml/min.Headspace sampling, head space equilibration time 30 minutes.
(2), the preparation of inner mark solution: get ethanol and be about 10mg, accurately weighed, put in 50ml measuring bottle, use methyl alcohol dissolved dilution, shake up, as inner mark solution.
(3), get this product and be about 0.1g, accurately weighed, in top set empty bottle, precision adds inner mark solution 2ml, as need testing solution; It is appropriate that another precision takes chloroform reference substance, makes every 1ml about containing the solution of chloroform 0.003mg with inner mark solution dilution, and precision measures 2ml and puts in advance precision weighing and add meclozine hydrochloride sample and be about in the ml headspace bottle of 0.1g, product solution in contrast.
(4), need testing solution and reference substance solution is got, headspace sampling, record chromatogram.By standard addition method, with the residual quantity of calculated by peak area chloroform.
Under this condition, methyl alcohol, ethanol and chloroform all can baseline separation, and chloroform chromatogram peak-to-peak type is better, and baseline is comparatively steady, can the residual quantity of Accurate Determining chloroform.
Embodiment 3:
(1), chromatographic condition
Instrument: Agilent 7820A gas chromatograph, Agilent 7694E head-space sampler.Stationary liquid is the capillary gas chromatographic column of (5%)-diphenyl-(95%)-dimethyl polysiloxane; Detecting device is electron capture detector (ECD), detector temperature 250 DEG C; Injector temperature 180 DEG C; Column temperature 45 DEG C, maintains 25 minutes, rear operation 200 DEG C, maintains 15 minutes.Carrier gas is nitrogen, flow rate of carrier gas: 5ml/min.Headspace sampling, head space equilibration time 20 minutes.
(2), get this product and be about 0.1g, accurately weighed, in top set empty bottle, precision adds ethanol 2ml, as need testing solution; It is appropriate that another precision takes chloroform reference substance, makes every 1ml about containing the solution of chloroform 0.003mg with ethanol dilution, and precision measures 2ml and puts in advance precision weighing and add meclozine hydrochloride sample and be about in the ml headspace bottle of 0.1g, product solution in contrast.
(3), need testing solution and reference substance solution is got, headspace sampling, record chromatogram.By standard addition method, with the residual quantity of calculated by peak area chloroform.
Under this condition, ethanol and chloroform can baseline separation, and chloroform chromatogram peak-to-peak type is better, and baseline is comparatively steady, can the residual quantity of Accurate Determining chloroform, and chromatogram is shown in Figure 18.
Embodiment 4:
(1), chromatographic condition
Instrument: Agilent 7820A gas chromatograph, Agilent 7694E head-space sampler.Stationary liquid is the capillary gas chromatographic column of (14%)-cyanogen propylbenzene-(86%)-dimethyl polysiloxane; Detecting device is electron capture detector (ECD), detector temperature 250 DEG C; Injector temperature 200 DEG C; Column temperature 50 DEG C, maintains 20 minutes, rear operation 220 DEG C, maintains 5 minutes.Carrier gas is nitrogen, flow rate of carrier gas: 3ml/min.Headspace sampling, head space equilibration time 45 minutes.
(2), get this product and be about 0.2g, accurately weighed, in top set empty bottle, precision adds dimethyl sulfoxide 1ml, as need testing solution; It is appropriate that another precision takes chloroform reference substance, makes every 1ml about containing the solution of chloroform 0.012mg with dimethyl sulfoxide dilution, and precision measures 1ml and puts in advance precision weighing and add meclozine hydrochloride sample and be about in the ml headspace bottle of 0.2g, product solution in contrast.
(3), need testing solution and reference substance solution is got, headspace sampling, record chromatogram.By standard addition method, with the residual quantity of calculated by peak area chloroform.
Under this condition, dimethyl sulfoxide and chloroform can baseline separation, and chloroform chromatogram peak-to-peak type is better, and baseline is comparatively steady, can the residual quantity of Accurate Determining chloroform, and chromatogram is shown in Figure 19.
Embodiment 5:
(1), chromatographic condition
Instrument: Agilent 7820A gas chromatograph, Agilent 7694E head-space sampler.Stationary liquid is the capillary gas chromatographic column of (6%)-cyanogen propylbenzene-(94%)-dimethyl polysiloxane; Detecting device is electron capture detector (ECD), detector temperature 300 DEG C; Injector temperature 250 DEG C; Column temperature 55 DEG C, maintains 10 minutes, rear operation 200 DEG C, maintains 5 minutes.Carrier gas is nitrogen, flow rate of carrier gas: 1ml/min.Headspace sampling, head space equilibration time 60 minutes.
(2), get this product and be about 0.1g, accurately weighed, in top set empty bottle, precision adds tert-butyl alcohol 2ml, as need testing solution; It is appropriate that another precision takes chloroform reference substance, makes every 1ml about containing the solution of chloroform 0.003mg with tert-butyl alcohol dilution, and precision measures 2ml and puts in advance precision weighing and add meclozine hydrochloride sample and be about in the ml headspace bottle of 0.1g, product solution in contrast.
(3), need testing solution and reference substance solution is got, headspace sampling, record chromatogram.By standard addition method, with the residual quantity of calculated by peak area chloroform.
Under this condition, the tert-butyl alcohol and chloroform can baseline separation, and chloroform chromatogram peak-to-peak type is better, and baseline is comparatively steady, can the residual quantity of Accurate Determining chloroform, and chromatogram is shown in Figure 20.
Embodiment 6:
(1), chromatographic condition
Instrument: Agilent 7820A gas chromatograph, Agilent 7694E head-space sampler.Stationary liquid is the capillary gas chromatographic column of dimethyl polysiloxane; Detecting device is electron capture detector (ECD), detector temperature 300 DEG C; Injector temperature 275 DEG C; Column temperature 60 DEG C, maintains 8 minutes, rear operation 200 DEG C, maintains 5 minutes.Carrier gas is nitrogen, flow rate of carrier gas: 3ml/min.Headspace sampling, head space equilibration time 30 minutes.
(2), get this product and be about 0.1g, accurately weighed, in top set empty bottle, precision adds cyclohexane 2ml, as need testing solution; It is appropriate that another precision takes chloroform reference substance, makes every 1ml about containing the solution of chloroform 0.003mg with cyclohexane dilution, and precision measures 2ml and puts in advance precision weighing and add meclozine hydrochloride sample and be about in the ml headspace bottle of 0.1g, product solution in contrast.
(3), need testing solution and reference substance solution is got, headspace sampling, record chromatogram.By standard addition method, with the residual quantity of calculated by peak area chloroform.
Under this condition, cyclohexane and chloroform can baseline separation, and chloroform chromatogram peak-to-peak type is better, and baseline is comparatively steady, can the residual quantity of Accurate Determining chloroform, and chromatogram is shown in Figure 21.
Embodiment 7:
(1), chromatographic condition
Instrument: Agilent 7820A gas chromatograph, Agilent 7694E head-space sampler.Stationary liquid is the capillary gas chromatographic column of (35%)-diphenyl-(65%)-dimethyl polysiloxane; Detecting device is electron capture detector (ECD), detector temperature 200 DEG C; Injector temperature 170 DEG C; Column temperature 40 DEG C, maintains 30 minutes, rear operation 180 DEG C, maintains 30 minutes.Carrier gas is helium, flow rate of carrier gas: 10ml/min.Headspace sampling, head space equilibration time 20 minutes.
(2), get this product and be about 0.05g, accurately weighed, in top set empty bottle, precision adds heptane 1ml, as need testing solution; It is appropriate that another precision takes chloroform reference substance, makes every 1ml about containing the solution of chloroform 0.001mg with heptane dilution, and precision measures 1ml and puts in advance precision weighing and add meclozine hydrochloride sample and be about in the ml headspace bottle of 0.05g, product solution in contrast.
(3), need testing solution and reference substance solution is got, headspace sampling, record chromatogram.By standard addition method, with the residual quantity of calculated by peak area chloroform.
Under this condition, heptane and chloroform can baseline separation, and chloroform chromatogram peak-to-peak type is better, and baseline is comparatively steady, can the residual quantity of Accurate Determining chloroform, and chromatogram is shown in Figure 22.
Embodiment 8:
(1), chromatographic condition
Instrument: Agilent 7820A gas chromatograph, Agilent 7694E head-space sampler.Stationary liquid is the capillary gas chromatographic column of (6%)-cyanogen propylbenzene-(94%)-dimethyl polysiloxane; Detecting device is electron capture detector (ECD), detector temperature 300 DEG C; Injector temperature 250 DEG C; Column temperature 45 DEG C, maintains 15 minutes, rear operation 200 DEG C, maintains 5 minutes.Carrier gas is nitrogen, flow rate of carrier gas: 3ml/min.Headspace sampling, head space equilibration time 30 minutes.
(2), get this product and be about 0.3g, accurately weighed, in top set empty bottle, precision adds DMF 6ml, as need testing solution; It is appropriate that another precision takes chloroform reference substance, makes every 1ml about containing the solution of chloroform 0.001mg with DMF dilution, and precision measures 6ml and puts in advance precision weighing and add meclozine hydrochloride sample and be about in the ml headspace bottle of 0.3g, product solution in contrast.
(3), need testing solution and reference substance solution is got, headspace sampling, record chromatogram.By standard addition method, with the residual quantity of calculated by peak area chloroform.
Under this condition, DMF and chloroform can baseline separation, and chloroform chromatogram peak-to-peak type is better, and baseline is comparatively steady, can the residual quantity of Accurate Determining chloroform, and chromatogram is shown in Figure 23.
Embodiment 9:
(1), chromatographic condition
Instrument: Agilent 7820A gas chromatograph, Agilent 7694E head-space sampler.Stationary liquid is the capillary gas chromatographic column of (6%)-cyanogen propylbenzene-(94%)-dimethyl polysiloxane; Detecting device is electron capture detector (ECD), detector temperature 300 DEG C; Injector temperature 250 DEG C; Column temperature 45 DEG C, maintains 15 minutes, rear operation 200 DEG C, maintains 5 minutes.Carrier gas is nitrogen, flow rate of carrier gas: 3ml/min.Headspace sampling, head space equilibration time 30 minutes.
(2), get this product and be about 0.1g, accurately weighed, in top set empty bottle, precision adds isopropyl alcohol 2ml, as need testing solution; It is appropriate that another precision takes chloroform reference substance, makes every 1ml about containing the solution of chloroform 0.003mg by isopropanol, and precision measures 2ml and puts in advance precision weighing and add meclozine hydrochloride sample and be about in the ml headspace bottle of 0.1g, product solution in contrast.
(3), need testing solution and reference substance solution is got, headspace sampling, record chromatogram.By standard addition method, with the residual quantity of calculated by peak area chloroform.
Under this condition, isopropyl alcohol and chloroform can baseline separation, and chloroform chromatogram peak-to-peak type is better, and baseline is comparatively steady, can the residual quantity of Accurate Determining chloroform, and chromatogram is shown in Figure 24.
Claims (18)
1. the method for separating and analyzing of chloroform residual quantity in meclozine hydrochloride, is characterized in that, comprising:
1) chromatographic condition:
Gas chromatograph, electron capture detector;
The temperature of electron capture detector is 200 DEG C ~ 300 DEG C; Injector temperature 170 DEG C ~ 275 DEG C;
Gas chromatograph chromatographic column used is capillary gas chromatographic column; Described capillary gas chromatographic column with following material for Stationary liquid: dimethyl polysiloxane, 5%-diphenyl-95%-dimethyl polysiloxane, 6%-cyanogen propylbenzene-94%-dimethyl polysiloxane, 35%-diphenyl-65%-dimethyl polysiloxane or 14%-cyanogen propylbenzene-86%-dimethyl polysiloxane;
The column temperature of described capillary gas chromatographic column is 40 DEG C ~ 60 DEG C, described column temperature maintains 8 minutes ~ 30 minutes, described chromatographic condition also comprises working procedure after a chromatographic column, after described chromatographic column, working procedure is for be set to 180 DEG C ~ 220 DEG C by column temperature, and after described chromatographic column, working procedure column temperature maintains 5 minutes ~ 30 minutes;
Carrier gas is nitrogen or helium, flow rate of carrier gas: 1ml/min ~ 10ml/min;
2) preparation process of need testing solution:
Get meclozine hydrochloride 0.05g ~ 0.3g, accurately weighed, in top set empty bottle, precision adds 1ml ~ 6ml test sample solvent, as need testing solution; Described test sample solvent is methyl alcohol, ethanol, isopropyl alcohol, the tert-butyl alcohol, cyclohexane, heptane, DMF or dimethyl sulfoxide (DMSO);
3) preparation process of reference substance solution:
Get chloroform appropriate, accurately weighed, make every 1ml containing the solution of chloroform 0.001mg ~ 0.012mg with described test sample solvent dilution, precision measures 1ml ~ 6ml and puts in advance precision weighing and add in the ml headspace bottle of 0.05g ~ 0.3g meclozine hydrochloride sample, product solution in contrast;
4) determination step:
Get described need testing solution and described reference substance solution, headspace sampling, head space equilibration time 20 ~ 60 minutes; Record chromatogram.
2. as described in claim 1 method for separating and analyzing, is characterized in that step 2) and 3) described in solvent be methyl alcohol, ethanol, isopropyl alcohol, DMF or dimethyl sulfoxide (DMSO).
3. as described in claim 1 method for separating and analyzing, is characterized in that step 2) and 3) described in solvent be methyl alcohol, ethanol or isopropyl alcohol.
4. as described in claim 1 method for separating and analyzing, is characterized in that step 2) and 3) described in solvent be methyl alcohol.
5. method for separating and analyzing as described in claim 1, is characterized in that described column temperature is 45 DEG C; Described column temperature maintains 15 minutes.
6. method for separating and analyzing as described in claim 1, it is characterized in that described rear working procedure column temperature 200 DEG C, described rear working procedure column temperature maintains 5 minutes.
7. method for separating and analyzing as described in claim 1, is characterized in that described head space equilibration time is 30 minutes.
8. method for separating and analyzing as described in claim 1, is characterized in that described injector temperature is 250 DEG C.
9. method for separating and analyzing as described in claim 1, is characterized in that described detector temperature is 300 DEG C.
10. method for separating and analyzing as described in claim 1, is characterized in that described flow rate of carrier gas is 3ml/min.
11. method for separating and analyzing as described in claim 1, is characterized in that step 2) described in the preparation process of need testing solution also comprise and dissolve test sample with inner mark solution,
Wherein, the compound method of described inner mark solution is: get interior mark and add step 2) in test sample solvent be mixed with the solution of 0.05mg/ml ~ 0.5mg/ml; Ethanol, isopropyl alcohol, the tert-butyl alcohol, cyclohexane or heptane is designated as in described, and different from described test sample solvent; When described test sample solvent is methyl alcohol, in described, be designated as ethanol.
12. method for separating and analyzing as described in claim 1, is characterized in that step 2) described in the preparation process of need testing solution also comprise and dissolve test sample with inner mark solution,
Wherein, the compound method of described inner mark solution is: get interior mark and add step 2) in test sample solvent be mixed with the solution of 0.1mg/ml; Ethanol, isopropyl alcohol, the tert-butyl alcohol, cyclohexane or heptane is designated as in described, and different from described test sample solvent; When described test sample solvent is methyl alcohol, in described, be designated as ethanol.
13. method for separating and analyzing as described in claim 1, is characterized in that step 3) described in the preparation process of reference substance solution also comprise and dissolve chloroform with inner mark solution,
Wherein, the compound method of described inner mark solution is: get interior mark and add step 2) in test sample solvent be mixed with the solution of 0.05mg/ml ~ 0.5mg/ml; Ethanol, isopropyl alcohol, the tert-butyl alcohol, cyclohexane or heptane is designated as in described, and different from described test sample solvent; When described test sample solvent is methyl alcohol, in described, be designated as ethanol.
14. method for separating and analyzing as described in claim 1, is characterized in that step 3) described in the preparation process of reference substance solution also comprise and dissolve chloroform with inner mark solution,
Wherein, the compound method of described inner mark solution is: get interior mark and add step 2) in test sample solvent be mixed with the solution of 0.1mg/ml; Ethanol, isopropyl alcohol, the tert-butyl alcohol, cyclohexane or heptane is designated as in described, and different from described test sample solvent; When described test sample solvent is methyl alcohol, in described, be designated as ethanol.
15. method for separating and analyzing as described in claim 1, is characterized in that described capillary gas chromatographic column is the capillary chromatographic column that is Stationary liquid with 6%-cyanogen propylbenzene-94%-dimethyl polysiloxane.
16. method for separating and analyzing as claimed in claim 1, is characterized in that, comprising:
1) chromatographic condition:
Gas chromatograph, electron capture detector;
The temperature of electron capture detector is 300 DEG C; Injector temperature 250 DEG C;
Gas chromatograph chromatographic column used is capillary gas chromatographic column; Described capillary gas chromatographic column is 6% cyanogen propylbenzene-94% dimethyl polysiloxane multipolymer is the capillary column of Stationary liquid;
The column temperature of described capillary gas chromatographic column is 45 DEG C, and described column temperature maintains 15 minutes;
Described chromatographic condition also comprises working procedure after a chromatographic column, and after described chromatographic column, working procedure is for be set to 200 DEG C by column temperature, and after described chromatographic column, working procedure column temperature maintains 5 minutes;
Carrier gas is nitrogen or helium, flow rate of carrier gas: 1ml/min ~ 10ml/min;
2) preparation process of need testing solution:
Get meclozine hydrochloride 0.05g ~ 0.3g, accurately weighed, in top set empty bottle, precision adds 1ml ~ 6ml test sample solvent, as need testing solution; Described test sample solvent is methyl alcohol, ethanol, isopropyl alcohol, the tert-butyl alcohol, cyclohexane, heptane, DMF or dimethyl sulfoxide (DMSO);
3) preparation process of reference substance solution:
Get chloroform appropriate, accurately weighed, make every 1ml containing the solution of chloroform 0.001mg ~ 0.012mg with described test sample solvent dilution, precision measures 1ml ~ 6ml and puts in advance precision weighing and add in the ml headspace bottle of 0.05g ~ 0.3g meclozine hydrochloride sample, product solution in contrast;
4) determination step:
Get described need testing solution and described reference substance solution, headspace sampling, head space equilibration time 20 ~ 60 minutes; Record chromatogram.
17. method for separating and analyzing as claimed in claim 1, is characterized in that, comprise following step:
1) chromatographic condition:
Gas chromatograph, electron capture detector;
The temperature of electron capture detector is 300 DEG C; Injector temperature 250 DEG C;
Gas chromatograph chromatographic column used is capillary gas chromatographic column; Described capillary gas chromatographic column is 6% cyanogen propylbenzene-94% dimethyl polysiloxane multipolymer is the capillary column of Stationary liquid;
The column temperature of described capillary gas chromatographic column is 45 DEG C, described column temperature maintains 15 minutes, described chromatographic condition also comprises working procedure after a chromatographic column, and after described chromatographic column, working procedure is for be set to 200 DEG C by column temperature, and after described chromatographic column, working procedure column temperature maintains 5 minutes;
Carrier gas is nitrogen, flow rate of carrier gas: 3ml/min;
2) preparation process of need testing solution:
Get meclozine hydrochloride 0.1g, accurately weighed, in top set empty bottle, precision adds 2ml methyl alcohol, as need testing solution;
3) preparation process of reference substance solution:
Get chloroform reference substance, accurately weighed, make every 1ml containing the solution of chloroform 0.003mg with methanol dilution, precision measures 2ml and puts in advance precision weighing and add in the ml headspace bottle of 0.1g meclozine hydrochloride sample, product solution in contrast;
4) determination step:
Get need testing solution and reference substance solution, headspace sampling, head space equilibration time 30 minutes; Record chromatogram.
18. method for separating and analyzing as claimed in claim 1, it is characterized in that, the chloroform in described meclozine hydrochloride is present in all kinds of formulations of tablet, injection or injection.
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| CN111122766A (en) * | 2018-10-31 | 2020-05-08 | Tcl集团股份有限公司 | Method for detecting chloroform in sulfur-containing quantum dot solution |
| CN109507329A (en) * | 2018-12-26 | 2019-03-22 | 蓝星（成都）新材料有限公司 | A kind of method that gas-chromatography surveys chloroform content in raffinate |
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