CN103543231A - Separation analysis method of residual amount of chloroform in meclizine dihydrochloride - Google Patents
Separation analysis method of residual amount of chloroform in meclizine dihydrochloride Download PDFInfo
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Abstract
The invention discloses a separation analysis method of the residual amount of chloroform in meclizine dihydrochloride. The separation analysis method is characterized in that a gas chromatographic (GC) method and an electron capture detector (ECD) are used for the separation analysis of the residual amount of the chloroform in the meclizine dihydrochloride. The separation analysis method can be used for overcoming the shortcoming that when a gas chromatographic method of a conventional flame ionization detector (FID) is used for detection, the response value of the chloroform is low, has the advantages that the response value of the chloroform is high, the sensitivity is high, and the operation is simple and convenient, and provides technical reference for the establishment of the quality standard for the residual amount of chloroform in medicinal raw materials.
Description
Technical field
The present invention relates to a kind of method for separating and analyzing of sample.The method for separating and analyzing that particularly relates to 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 is the antagonist of histamine receptor, be applicable to various mucocutaneous anaphylactic diseases, and also can be used for nauseating, vomiting that gestation, radiotherapy and motion sickness cause.Its effect is lasting far beyond diphenhydramine, can maintain 12～24 hours.In Chinese Pharmacopoeia version in 2010, the residual solvent item of using in this kind building-up process is not investigated.Meclozine hydrochloride synthesis technique is as follows:
When synthetic, used chloroform equal solvent, according to International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human use view, be the classification in ICH (International Conference on Harmonization OF Technical Requirements for Registration of Pharmaceuticals for Human Use), chloroform is two kind solvents.For the strict drug quality of controlling, guarantee the safe and effective of its clinical application, should check the residual quantity of chloroform in meclozine hydrochloride.In other medicinal compounds, once used flame ionization ditector (FID) method to detect chloroform, but the inventor tests and find to adopt flame ionization ditector (FID), chloroform response is too low, cannot Accurate Determining sample in the residual quantity of chloroform.The low shortcoming of chloroform response when the vapor-phase chromatography that the method that the inventor sets up has overcome traditional flame ionization ditector (FID) detects, the response of newly-established method chloroform is high, highly sensitive, easy and simple to handle, can accurately 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 low shortcoming of chloroform response when the vapor-phase chromatography that method of the present invention has overcome traditional flame ionization ditector (FID) detects.In the method, the response of chloroform is high, highly sensitive, easy and simple to handle, for the foundation of chloroform residual quantity quality standard in other bulk drug 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 ℃ ~ 300 ℃; 170 ℃ ~ 275 ℃ of injector temperatures;
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 ℃ ~ 60 ℃, described column temperature maintains 8 minutes ~ and 30 minutes, described chromatographic condition also comprises working procedure after a chromatographic column, after described chromatographic column, working procedure is set to 180 ℃ ~ 220 ℃ for column temperature, after described chromatographic column working procedure column temperature maintain 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, with solvent dilution, make every 1ml containing the solution of chloroform 0.001mg ~ 0.012mg, precision measures 1ml ~ 6ml and puts in advance precision weighing and add in the head space bottle of 0.05g ~ 0.3g meclozine hydrochloride sample, in contrast product solution.
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.Methyl alcohol most preferably.
Preferably, described column temperature is 45 ℃; Described column temperature maintains 15 minutes.
Preferably, 200 ℃ of described rear operation column temperatures, described rear operation column temperature maintains 5 minutes.
Preferably, described head space equilibration time is 30 minutes.
Preferably, described injector temperature is 250 ℃.
Preferably, described detector temperature is 300 ℃.
Preferably, described flow rate of carrier gas is 3ml/min.
Need testing solution preparation method of the present invention can also be: the preparation method of the need testing solution step 2) can also be for dissolving test sample with inner mark solution, in described, be designated as ethanol, isopropyl alcohol, the tert-butyl alcohol, cyclohexane, heptane, 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: the preparation method of the reference substance solution described in step 3) can also be for dissolving chloroform with inner mark solution, in described, be designated as ethanol, isopropyl alcohol, the tert-butyl alcohol, cyclohexane, heptane, 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 of described nonpolar, low pole and middle polarity is to take following material as the fixing capillary chromatographic column of phase: 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 take 6%-cyanogen propylbenzene-94%-dimethyl polysiloxane as the fixing capillary chromatographic column of phase.
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 ℃; 250 ℃ of injector temperatures;
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 fixing capillary column of phase;
The column temperature of described capillary gas chromatographic column is 45 ℃, 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 set to 200 ℃ for 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, with solvent dilution, make every 1ml containing the solution of chloroform 0.001mg ~ 0.012mg, precision measures 1ml ~ 6ml and puts in advance precision weighing and add in the head space bottle of 0.05g ~ 0.3g meclozine hydrochloride sample, in contrast product solution.
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 ℃; 250 ℃ of injector temperatures;
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 fixing capillary column of phase;
The column temperature of described capillary gas chromatographic column is 45 ℃, 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 set to 200 ℃ for 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, with methyl alcohol dilution, make every 1ml containing the solution of chloroform 0.003mg, precision measures 2ml and puts in advance precision weighing and add in the head space bottle of 0.1g meclozine hydrochloride sample, in contrast product solution;
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 be effectively separated with chloroform, do not disturb the detection of chloroform.Therefore above-mentioned solvent can be as the solvent that detects chloroform residual quantity in meclozine hydrochloride.With methyl alcohol, make solvent, 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 fixing capillary chromatographic column that is respectively mutually 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 for the separation of meclozine hydrochloride chloroform.Wherein fixing is that the chromatographic column of (6%)-cyanogen propylbenzene-(94%)-dimethyl polysiloxane is comparatively conventional mutually, and polarity is moderate, chloroform chromatogram peak-to-peak type is better, therefore preferably fixing, is the capillary chromatographic column of (6%)-cyanogen propylbenzene-(94%)-dimethyl polysiloxane mutually.
The determination method of chloroform residual quantity: for peak area, calculate 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 low shortcoming of chloroform response while adopting traditional flame ionization ditector (FID) to detect.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 ℃, 80 ℃, it is too fast that chloroform goes out peak, and during solvent baseline lack of equilibrium, chloroform has just gone out peak, and the hangover of chloroform peak type, affects the accurate calculating of chloroform residual quantity.And chromatogram column temperature is while being 60 ℃, 45 ℃, 40 ℃, baseline is more steady, and chloroform chromatogram peak-to-peak type is more symmetrical, and the retention time of solvent peak and chloroform is more moderate, can accurately calculate the residual quantity of chloroform.Be preferably 40 ℃ ~ 60 ℃ of chromatographic column column temperatures, more preferably 45 ℃, maintain 15 minutes.
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, while finding that chromatographic column takes degree such as grade rear working procedure not to be set, baseline is not steady, cannot Accurate Determining chloroform content; When chromatogram column temperature is taked 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 that rear working procedure is set, baseline is more steady, and chloroform chromatogram peak-to-peak type is symmetrical, can Accurate Determining chloroform content.Be 40 ℃ ~ 60 ℃ of the preferred column temperatures of chromatogram column temperature, maintain 8 minutes ~ 30 minutes, 180 ℃ ~ 220 ℃ of rear operation column temperatures, maintain 5 minutes ~ 30 minutes; More preferably column temperature is 45 ℃, maintains 15 minutes, and 200 ℃ of rear operations, maintain 5 minutes.
4, chloroform determination of residual amount method-standard addition method
Checking is found by experiment, while adopting external standard method, and owing to there being 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, to learn, head space balance is in the time of 10 minutes, 15 minutes, and chloroform gas volatilization not exclusively, can not Accurate Determining chloroform residual quantity; Head space balance is in the time of 20 minutes ~ 60 minutes, chloroform gas volatilization completely, residual quantity that can Accurate Determining chloroform.Preferably head space balance is 30 minutes.
Accompanying drawing explanation
Fig. 1: solvent methanol location GC chromatogram;
Fig. 2: chloroform location GC chromatogram;
Fig. 3: 1 time chloroform reference substance GC chromatogram of condition;
Fig. 4: 5 times chloroform reference substance GC chromatograms of condition;
Fig. 5: 6 times chloroform reference substance GC chromatograms of condition;
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 chromatograms;
Figure 19: embodiment 4 sample GC chromatograms;
Figure 20: embodiment 5 sample GC chromatograms;
Figure 21: embodiment 6 sample GC chromatograms;
Figure 22: embodiment 7 sample GC chromatograms;
Figure 23: embodiment 8 sample GC chromatograms;
Figure 24: embodiment 9 sample GC chromatograms.
Embodiment
Below by embodiment and with reference to the description of accompanying drawing, the invention will be further described, but this is not limitation of the present invention, those skilled in the art are according to basic thought of the present invention, can make various modifications or improvement, but only otherwise depart from basic thought of the present invention, all within the scope of the present invention.
Experimental example 1:
Experiment title: 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.Adopt (6%) cyanogen propylbenzene-(94%) dimethyl polysiloxane multipolymer for the fixing capillary column of phase (30m * 0.53mm * 3.0 μ m), adopt electron capture detector (ECD), 300 ℃ of detector temperatures, 250 ℃ of injector temperatures, carrier gas nitrogen, flow rate of carrier gas is per minute 3ml;
Chromatogram column temperature: adopt respectively 100 ℃, 80 ℃, 60 ℃, 45 ℃, maintain 6-15 minute;
200 ℃ of rear operations, maintain 5 minutes; Or rear working procedure is not set;
Head space equilibration time 10,15,30,60 minutes;
Get chloroform reference substance appropriate, with methyl alcohol dilution, make every 1ml approximately containing the solution of chloroform 0.003mg, precision measures 2ml and puts in advance precision weighing and add in the head space bottle of the about 0.1g of meclozine hydrochloride sample,
Experimental result: in Table 1
In meclozine hydrochloride, in chloroform determination of residual amount method, the inventor is optimized chromatogram column temperature condition, to whether needing rear operation to carry out comparative study, 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 is undesirable, and condition 4,5,6,7 all meets the requirements.
By the screening of above-mentioned chromatogram column temperature condition, in the time of chromatogram column temperature 40-60 ℃, chromatogram peak-to-peak type is better, and baseline is more steady.Optimum in the time of 45 ℃.
Add after rear working procedure, contribute to baseline steady, chloroform peak type is better.Preferably, operation is 200 ℃, keeps the condition of 5 minutes.
Head space equilibration time all meets the requirements for 30-60 minute, and preferably balance is 30 minutes.
Chloroform residue checking in meclozine hydrochloride: highly sensitive by method validation evidence the method for the invention such as linear test, sample introduction precision test, replica test, minimum detectability and the test of minimum quantitative limit, recovery tests, accuracy good, can Accurate Determining go out the residual quantity of chloroform in meclozine hydrochloride.
Experimental example 2:
Experiment title: chloroform residue checking-linear test in meclozine hydrochloride
Experiment purpose: the range of linearity of verifying chloroform residue in meclozine hydrochloride by linear test
Experimental technique: Agilent 7820A gas chromatograph, Agilent 7694E head-space sampler.Adopt (6%) cyanogen propylbenzene-(94%) dimethyl polysiloxane multipolymer for the fixing capillary column of phase (30m * 0.53mm * 3.0 μ m), adopt electron capture detector (ECD), 300 ℃ of detector temperatures, 250 ℃ of injector temperatures, carrier gas nitrogen, flow rate of carrier gas is per minute 3ml; Chromatogram column temperature: 45 ℃ maintain 15 minutes, 200 ℃ of rear operations, maintain 5 minutes; Head space equilibration time 30 minutes.
Get the about 16.5mg of chloroform, accurately weighed, put in 25ml measuring bottle, with methyl alcohol, be diluted to scale, shake up, as strong solution.It is appropriate that precision measures strong solution respectively, with methyl alcohol, is diluted to the solution that concentration is respectively 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, shakes up.Headspace sampling in the accurate solution 2ml top set empty bottle that measures each concentration, records chromatogram respectively, with concentration and peak area, does linear regression.
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-mentionedly experimental results show 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 title: 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.Adopt (6%) cyanogen propylbenzene-(94%) dimethyl polysiloxane multipolymer for the fixing capillary column of phase (30m * 0.53mm * 3.0 μ m), adopt electron capture detector (ECD), 300 ℃ of detector temperatures, 250 ℃ of injector temperatures, carrier gas nitrogen, flow rate of carrier gas is per minute 3ml; Chromatogram column temperature: 45 ℃ maintain 15 minutes, 200 ℃ of rear operations, maintain 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 times of noise, the concentration limit that records chloroform is 4.95ng/ml.
In 10 times of noise, 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, method is enough sensitive.
Experimental example 4:
Experiment title: chloroform residue checking-Precision Experiment in meclozine hydrochloride
Experiment purpose: the precision of verifying chloroform residue in meclozine hydrochloride by precision
Experimental technique: Agilent 7820A gas chromatograph, Agilent 7694E head-space sampler.Adopt (6%) cyanogen propylbenzene-(94%) dimethyl polysiloxane multipolymer for the fixing capillary column of phase (30m * 0.53mm * 3.0 μ m), adopt electron capture detector (ECD), 300 ℃ of detector temperatures, 250 ℃ of injector temperatures, carrier gas nitrogen, flow rate of carrier gas is per minute 3ml; Chromatogram column temperature: 45 ℃ maintain 15 minutes, 200 ℃ of rear operations, maintain 5 minutes; Head space equilibration time 30 minutes;
The solution of getting 3.3 μ g/ml in chloroform linear test, precision measures 2ml, in top set empty bottle, 6 parts of parallel preparations, headspace sampling, records chromatogram.The RSD% that calculates 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 title: chloroform residue checking-repeated experiment in meclozine hydrochloride
Experiment purpose: the repeatability of verifying chloroform residue in meclozine hydrochloride by repeated experiment
Experimental technique: Agilent7820A gas chromatograph, Agilent7694E head-space sampler.Adopt (6%) cyanogen propylbenzene-(94%) dimethyl polysiloxane multipolymer for the fixing capillary column of phase (30m * 0.53mm * 3.0 μ m), adopt electron capture detector (ECD), 300 ℃ of detector temperatures, 250 ℃ of injector temperatures, carrier gas nitrogen, flow rate of carrier gas is per minute 3ml; Chromatogram column temperature: 45 ℃ maintain 15 minutes, 200 ℃ of rear operations, maintain 5 minutes; Head space equilibration time 30 minutes, headspace sampling.
Get the about 0.1g of this product, 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, with methyl alcohol dilution, makes every 1ml approximately containing the solution of chloroform 0.003mg, and precision measures 2ml and puts in advance precision weighing and add in the head space bottle of the about 0.1g of meclozine hydrochloride sample, in contrast product solution.Get need testing solution and reference substance solution.
Prepare respectively two parts of reference substance solution and six parts of need testing solutions, 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 duplicate samples, the measurement result of chloroform residual quantity is basically identical, repeatability better.
Experimental example 6:
Experiment title: 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.Adopt (6%) cyanogen propylbenzene-(94%) dimethyl polysiloxane multipolymer for the fixing capillary column of phase (30m * 0.53mm * 3.0 μ m), adopt electron capture detector (ECD), 300 ℃ of detector temperatures, 250 ℃ of injector temperatures, carrier gas nitrogen, flow rate of carrier gas is per minute 3ml; Chromatogram column temperature: 45 ℃ maintain 15 minutes, 200 ℃ of rear operations, maintain 5 minutes; Head space equilibration time 30 minutes, headspace sampling.
(1), the preparation of need testing solution: get the about 0.1g of this product, 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 the about 15mg of chloroform, accurately weighed, put in 25ml measuring bottle, with methyl alcohol, be diluted to scale, shake up, as stock solution; Precision measures storing solution 0.25ml and puts in 50ml measuring bottle, with methyl alcohol, is diluted to scale, shake up, and solution in contrast, precision measures the molten sample 2ml of contrast and puts in advance precision weighing and add in the head space bottle of the about 0.1g of meclozine hydrochloride sample, in contrast product solution;
(3), the preparation of recovery sample solution:
Precision measures stock solution 0.20ml, 0.25ml, 0.30ml, put respectively in 50ml measuring bottle, with methyl alcohol, be diluted to scale, shake up, as 80%, 100%, 120% contrast solution, the accurate 2ml that measures puts in advance precision weighing and adds in the head space bottle bottle of the about 0.1g of meclozine hydrochloride sample respectively, and 3 parts of each parallel preparations, as recovery sample solution;
Get need testing solution, reference substance solution and recovery sample solution, headspace sampling, records 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 duplicate samples 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 embodiment 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.Fixing is the capillary gas chromatographic column of (6%)-cyanogen propylbenzene-(94%)-dimethyl polysiloxane mutually; Detecting device is electron capture detector (ECD), 300 ℃ of detector temperatures; 250 ℃ of injector temperatures; 45 ℃ of column temperatures, maintain 15 minutes, and 200 ℃ of rear operations, maintain 5 minutes.Carrier gas is nitrogen, flow rate of carrier gas: 3ml/min.Headspace sampling, head space equilibration time 30 minutes.
(2), the about 0.1g of sample thief, 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, with methyl alcohol dilution, makes every 1ml approximately containing the solution of chloroform 0.003mg, and precision measures 2ml and puts in advance precision weighing and add in the head space bottle of the about 0.1g of meclozine hydrochloride sample, in contrast product solution.
(3), get need testing solution and reference substance solution, headspace sampling, records 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 more steady, residual quantity that can 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.Fixing is the capillary gas chromatographic column of (6%)-cyanogen propylbenzene-(94%)-dimethyl polysiloxane mutually; Detecting device is electron capture detector (ECD), 300 ℃ of detector temperatures; 250 ℃ of injector temperatures; 45 ℃ of column temperatures, maintain 15 minutes, and 200 ℃ of rear operations, maintain 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 the about 10mg of ethanol, accurately weighed, put in 50ml measuring bottle, use methyl alcohol dissolved dilution, shake up, as inner mark solution.
(3), get the about 0.1g of this product, 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, with inner mark solution dilution, makes every 1ml approximately containing the solution of chloroform 0.003mg, and precision measures 2ml and puts in advance precision weighing and add in the head space bottle of the about 0.1g of meclozine hydrochloride sample, in contrast product solution.
(4), get need testing solution and reference substance solution, headspace sampling, records 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 more steady, residual quantity that can Accurate Determining chloroform.
Embodiment 3:
(1), chromatographic condition
Instrument: Agilent 7820A gas chromatograph, Agilent 7694E head-space sampler.Fixing is the capillary gas chromatographic column of (5%)-diphenyl-(95%)-dimethyl polysiloxane mutually; Detecting device is electron capture detector (ECD), 250 ℃ of detector temperatures; 180 ℃ of injector temperatures; 45 ℃ of column temperatures, maintain 25 minutes, and 200 ℃ of rear operations, maintain 15 minutes.Carrier gas is nitrogen, flow rate of carrier gas: 5ml/min.Headspace sampling, head space equilibration time 20 minutes.
(2), get the about 0.1g of this product, 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, with ethanol dilution, makes every 1ml approximately containing the solution of chloroform 0.003mg, and precision measures 2ml and puts in advance precision weighing and add in the head space bottle of the about 0.1g of meclozine hydrochloride sample, in contrast product solution.
(3), get need testing solution and reference substance solution, headspace sampling, records 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 more steady, residual quantity that can 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.Fixing is the capillary gas chromatographic column of (14%)-cyanogen propylbenzene-(86%)-dimethyl polysiloxane mutually; Detecting device is electron capture detector (ECD), 250 ℃ of detector temperatures; 200 ℃ of injector temperatures; 50 ℃ of column temperatures, maintain 20 minutes, and 220 ℃ of rear operations, maintain 5 minutes.Carrier gas is nitrogen, flow rate of carrier gas: 3ml/min.Headspace sampling, head space equilibration time 45 minutes.
(2), get the about 0.2g of this product, 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, with dimethyl sulfoxide dilution, makes every 1ml approximately containing the solution of chloroform 0.012mg, and precision measures 1ml and puts in advance precision weighing and add in the head space bottle of the about 0.2g of meclozine hydrochloride sample, in contrast product solution.
(3), get need testing solution and reference substance solution, headspace sampling, records 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 more steady, residual quantity that can 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.Fixing is the capillary gas chromatographic column of (6%)-cyanogen propylbenzene-(94%)-dimethyl polysiloxane mutually; Detecting device is electron capture detector (ECD), 300 ℃ of detector temperatures; 250 ℃ of injector temperatures; 55 ℃ of column temperatures, maintain 10 minutes, and 200 ℃ of rear operations, maintain 5 minutes.Carrier gas is nitrogen, flow rate of carrier gas: 1ml/min.Headspace sampling, head space equilibration time 60 minutes.
(2), get the about 0.1g of this product, 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, with tert-butyl alcohol dilution, makes every 1ml approximately containing the solution of chloroform 0.003mg, and precision measures 2ml and puts in advance precision weighing and add in the head space bottle of the about 0.1g of meclozine hydrochloride sample, in contrast product solution.
(3), get need testing solution and reference substance solution, headspace sampling, records 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 more steady, residual quantity that can 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.Fixing is the capillary gas chromatographic column of dimethyl polysiloxane mutually; Detecting device is electron capture detector (ECD), 300 ℃ of detector temperatures; 275 ℃ of injector temperatures; 60 ℃ of column temperatures, maintain 8 minutes, and 200 ℃ of rear operations, maintain 5 minutes.Carrier gas is nitrogen, flow rate of carrier gas: 3ml/min.Headspace sampling, head space equilibration time 30 minutes.
(2), get the about 0.1g of this product, 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, with cyclohexane dilution, makes every 1ml approximately containing the solution of chloroform 0.003mg, and precision measures 2ml and puts in advance precision weighing and add in the head space bottle of the about 0.1g of meclozine hydrochloride sample, in contrast product solution.
(3), get need testing solution and reference substance solution, headspace sampling, records 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 more steady, residual quantity that can 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.Fixing is the capillary gas chromatographic column of (35%)-diphenyl-(65%)-dimethyl polysiloxane mutually; Detecting device is electron capture detector (ECD), 200 ℃ of detector temperatures; 170 ℃ of injector temperatures; 40 ℃ of column temperatures, maintain 30 minutes, and 180 ℃ of rear operations, maintain 30 minutes.Carrier gas is helium, flow rate of carrier gas: 10ml/min.Headspace sampling, head space equilibration time 20 minutes.
(2), get the about 0.05g of this product, 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, with heptane dilution, makes every 1ml approximately containing the solution of chloroform 0.001mg, and precision measures 1ml and puts in advance precision weighing and add in the head space bottle of the about 0.05g of meclozine hydrochloride sample, in contrast product solution.
(3), get need testing solution and reference substance solution, headspace sampling, records 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 more steady, residual quantity that can 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.Fixing is the capillary gas chromatographic column of (6%)-cyanogen propylbenzene-(94%)-dimethyl polysiloxane mutually; Detecting device is electron capture detector (ECD), 300 ℃ of detector temperatures; 250 ℃ of injector temperatures; 45 ℃ of column temperatures, maintain 15 minutes, and 200 ℃ of rear operations, maintain 5 minutes.Carrier gas is nitrogen, flow rate of carrier gas: 3ml/min.Headspace sampling, head space equilibration time 30 minutes.
(2), get the about 0.3g of this product, 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, with DMF dilution, makes every 1ml approximately containing the solution of chloroform 0.001mg, and precision measures 6ml and puts in advance precision weighing and add in the head space bottle of the about 0.3g of meclozine hydrochloride sample, in contrast product solution.
(3), get need testing solution and reference substance solution, headspace sampling, records 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 more steady, residual quantity that can 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.Fixing is the capillary gas chromatographic column of (6%)-cyanogen propylbenzene-(94%)-dimethyl polysiloxane mutually; Detecting device is electron capture detector (ECD), 300 ℃ of detector temperatures; 250 ℃ of injector temperatures; 45 ℃ of column temperatures, maintain 15 minutes, and 200 ℃ of rear operations, maintain 5 minutes.Carrier gas is nitrogen, flow rate of carrier gas: 3ml/min.Headspace sampling, head space equilibration time 30 minutes.
(2), get the about 0.1g of this product, 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, by isopropanol, makes every 1ml approximately containing the solution of chloroform 0.003mg, and precision measures 2ml and puts in advance precision weighing and add in the head space bottle of the about 0.1g of meclozine hydrochloride sample, in contrast product solution.
(3), get need testing solution and reference substance solution, headspace sampling, records 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 more steady, residual quantity that can Accurate Determining chloroform, and chromatogram is shown in Figure 24.
Claims (15)
1. a method for separating and analyzing for 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 ℃ ~ 300 ℃; 170 ℃ ~ 275 ℃ of injector temperatures;
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 ℃ ~ 60 ℃, described column temperature maintains 8 minutes ~ and 30 minutes, described chromatographic condition also comprises working procedure after a chromatographic column, after described chromatographic column, working procedure is set to 180 ℃ ~ 220 ℃ for column temperature, after described chromatographic column working procedure column temperature maintain 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 about 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, with described test sample solvent dilution, make every 1ml containing the solution of chloroform 0.001mg ~ 0.012mg, precision measures 1ml ~ 6ml and puts in advance precision weighing and add in the head space bottle of 0.05g ~ 0.3g meclozine hydrochloride sample, in contrast product solution;
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. method for separating and analyzing as described in claim 1, is characterized in that step 2) and 3) described in solvent be methyl alcohol, ethanol, isopropyl alcohol, DMF, dimethyl sulfoxide (DMSO); Particular methanol, ethanol, isopropyl alcohol; Methyl alcohol most preferably.
3. method for separating and analyzing as described in claim 1, is characterized in that described column temperature is 45 ℃; Described column temperature maintains 15 minutes.
4. method for separating and analyzing as described in claim 1, is characterized in that 200 ℃ of described rear working procedure column temperatures, and described rear working procedure column temperature maintains 5 minutes.
5. method for separating and analyzing as described in claim 1, is characterized in that described head space equilibration time is 30 minutes.
6. method for separating and analyzing as described in claim 1, is characterized in that described injector temperature is 250 ℃.
7. method for separating and analyzing as described in claim 1, is characterized in that described detector temperature is 300 ℃.
8. method for separating and analyzing as described in claim 1, is characterized in that described flow rate of carrier gas is 3ml/min.
9. method for separating and analyzing as described in claim 1, is characterized in that step 2) described in the preparation method of need testing solution also comprise with inner mark solution and dissolve test sample,
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; Preferably get interior mark and add step 2) in test sample solvent be mixed with the solution of 0.1mg/ml; In described, be designated as ethanol, isopropyl alcohol, the tert-butyl alcohol, cyclohexane, heptane, and different from described test sample solvent; When described test sample solvent is methyl alcohol, described interior mark is preferably ethanol.
10. method for separating and analyzing as described in claim 1, is characterized in that the preparation method of the reference substance solution described in step 3) also comprises with inner mark solution and dissolves chloroform,
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; Preferably get interior mark and add step 2) in test sample solvent be mixed with the solution of 0.1mg/ml; In described, be designated as ethanol, isopropyl alcohol, the tert-butyl alcohol, cyclohexane, heptane, and different from described test sample solvent; When described test sample solvent is methyl alcohol, described interior mark is preferably ethanol.
11. method for separating and analyzing as described in claim 1, the capillary chromatographic column that it is characterized in that described nonpolar, low pole and middle polarity is for take following material as the fixing capillary chromatographic column of phase: 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 take 6%-cyanogen propylbenzene-94%-dimethyl polysiloxane as the fixing capillary chromatographic column of phase.
12. method for separating and analyzing as described in claim 1, is characterized in that described capillary chromatographic column is middle polarity chromatographic column.
13. 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 ℃; 250 ℃ of injector temperatures;
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 fixing capillary column of phase;
The column temperature of described capillary gas chromatographic column is 45 ℃, 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 set to 200 ℃ for 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 about 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, with described test sample solvent dilution, make every 1ml containing the solution of chloroform 0.001mg ~ 0.012mg, precision measures 1ml ~ 6ml and puts in advance precision weighing and add in the head space bottle of 0.05g ~ 0.3g meclozine hydrochloride sample, in contrast product solution;
4) determination step:
Get described need testing solution and described reference substance solution, headspace sampling, head space equilibration time 20 ~ 60 minutes; Record chromatogram.
14. 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 ℃; 250 ℃ of injector temperatures;
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 fixing capillary column of phase;
The column temperature of described capillary gas chromatographic column is 45 ℃, 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 set to 200 ℃ for 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, with methyl alcohol dilution, make every 1ml containing the solution of chloroform 0.003mg, precision measures 2ml and puts in advance precision weighing and add in the head space bottle of 0.1g meclozine hydrochloride sample, in contrast product solution;
4) determination step:
Get need testing solution and reference substance solution, headspace sampling, head space equilibration time 30 minutes; Record chromatogram.
15. method for separating and analyzing as claimed in claim 1, 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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| 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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