CN103487541B - A kind of method simultaneously detecting multiple residual solvent in Ceftriaxone Sodium - Google Patents
A kind of method simultaneously detecting multiple residual solvent in Ceftriaxone Sodium Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 23
- 229960000479 ceftriaxone sodium Drugs 0.000 title claims abstract description 17
- FDRNWTJTHBSPMW-GNXCPKRQSA-L disodium;(6r,7r)-7-[[(2e)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-[(2-methyl-6-oxido-5-oxo-1,2,4-triazin-3-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound [Na+].[Na+].S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)/C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C([O-])=NN1C FDRNWTJTHBSPMW-GNXCPKRQSA-L 0.000 title claims abstract description 17
- 239000013557 residual solvent Substances 0.000 title claims abstract description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 71
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 70
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 69
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 63
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 63
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 60
- 239000003960 organic solvent Substances 0.000 claims abstract description 19
- 239000003814 drug Substances 0.000 claims abstract description 10
- 238000001514 detection method Methods 0.000 claims abstract description 6
- 238000004817 gas chromatography Methods 0.000 claims abstract description 6
- 238000004458 analytical method Methods 0.000 claims abstract description 5
- 229940079593 drug Drugs 0.000 claims abstract description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 49
- 238000012360 testing method Methods 0.000 claims description 44
- 239000013558 reference substance Substances 0.000 claims description 38
- 239000000523 sample Substances 0.000 claims description 24
- 238000002360 preparation method Methods 0.000 claims description 21
- 238000007789 sealing Methods 0.000 claims description 17
- 238000005070 sampling Methods 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 10
- 238000012417 linear regression Methods 0.000 claims description 8
- 239000012488 sample solution Substances 0.000 claims description 8
- 230000001174 ascending effect Effects 0.000 claims description 3
- 238000004364 calculation method Methods 0.000 claims description 3
- 239000012159 carrier gas Substances 0.000 claims description 3
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 238000011067 equilibration Methods 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 238000011084 recovery Methods 0.000 claims description 3
- 229920005573 silicon-containing polymer Polymers 0.000 claims description 3
- 239000000243 solution Substances 0.000 abstract description 62
- 238000009835 boiling Methods 0.000 abstract description 4
- 239000000463 material Substances 0.000 abstract description 4
- 238000002347 injection Methods 0.000 abstract description 3
- 239000007924 injection Substances 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 239000011159 matrix material Substances 0.000 abstract description 2
- 238000003822 preparative gas chromatography Methods 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 229960002727 cefotaxime sodium Drugs 0.000 description 6
- AZZMGZXNTDTSME-JUZDKLSSSA-M cefotaxime sodium Chemical compound [Na+].N([C@@H]1C(N2C(=C(COC(C)=O)CS[C@@H]21)C([O-])=O)=O)C(=O)\C(=N/OC)C1=CSC(N)=N1 AZZMGZXNTDTSME-JUZDKLSSSA-M 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000003988 headspace gas chromatography Methods 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 3
- NCFTXMQPRQZFMZ-WERGMSTESA-M Cefoperazone sodium Chemical compound [Na+].O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC(O)=CC=1)C(=O)N[C@@H]1C(=O)N2C(C([O-])=O)=C(CSC=3N(N=NN=3)C)CS[C@@H]21 NCFTXMQPRQZFMZ-WERGMSTESA-M 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- NKZMPZCWBSWAOX-IBTYICNHSA-M Sulbactam sodium Chemical compound [Na+].O=S1(=O)C(C)(C)[C@H](C([O-])=O)N2C(=O)C[C@H]21 NKZMPZCWBSWAOX-IBTYICNHSA-M 0.000 description 2
- 238000003965 capillary gas chromatography Methods 0.000 description 2
- 229960002417 cefoperazone sodium Drugs 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 229960000614 sulbactam sodium Drugs 0.000 description 2
- 206010007269 Carcinogenicity Diseases 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000007670 carcinogenicity Effects 0.000 description 1
- 231100000260 carcinogenicity Toxicity 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229940113088 dimethylacetamide Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- BCDGQXUMWHRQCB-UHFFFAOYSA-N glycine methyl ketone Natural products CC(=O)CN BCDGQXUMWHRQCB-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229940035429 isobutyl alcohol Drugs 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- BUTPBERGMJVRBM-UHFFFAOYSA-N methanol;methylsulfinylmethane Chemical compound OC.CS(C)=O BUTPBERGMJVRBM-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
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- Investigating Or Analysing Biological Materials (AREA)
- Sampling And Sample Adjustment (AREA)
Abstract
The present invention relates to a kind of method simultaneously detecting multiple residual solvent in Ceftriaxone Sodium, adopt gas chromatography analysis method, simultaneously methyl alcohol, ethanol, acetonitrile, acetone, ethyl acetate and triethylamine six kinds of organic solvents in detection of drugs.The present invention adopts vapor-phase chromatography to detect the content of 6 kinds of organic solvents simultaneously, and highly sensitive, reproducible, degree of accuracy is high; Use standard addition method, do not need other standard substance to make internal standard compound, only need predict the pure material of component, can matrix effect be offset, simple to operate; Adopt headspace injection method, avoid direct solution example to the interference detected and the pollution come chromatogram cornice; Adopt temperature programme method, can effectively be separated low boiling and high boiling organic solvent.
Description
Technical field
The present invention relates to a kind of detection method of gas chromatography, especially relate to the method simultaneously detecting multiple residual solvent in Ceftriaxone Sodium.
Background technology
Medicament residue solvent refers to the volatile organic chemistry material matter of use or generation in raw material, auxiliary material or formulation manufacturing processes.These fail the solvent be completely removed in process of production, and not only causing the stability of medicine to reduce affects quality, and clothes for patients with after can increase toxicity and carcinogenicity.International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human use view (InternationalConferenceonHarmonizationofTechnicalRequire mentsforRegistrationofPharmaceuticalsforHumanUse(ICH)) 69 kinds of conventional organic solvents in medicine production, purge process are divided into 4 classes according to the extent of injury of human body and environment.For first, second and third class solvent, within the residual quantity in pharmaceutical end product must control the limit required at ICH.
Because organic solvent is of a great variety, therefore, people are necessary to provide a kind of method that simultaneously can detect multiple organic solvent to monitor its content.
Wear the people such as Shou Feng and measure residual solvent in cefoperazone sodium and sulbactam sodium for injection at headspace capillary GC, straits medicine company 2012,24(2), report in 53-54, utilize methyl alcohol, ethanol, ether, acetone, isopropyl alcohol, acetonitrile, methylene chloride, normal hexane, n-propanol, ethyl acetate, tetrahydrofuran, cyclohexane, normal butyl alcohol and the methyl isobutyl ketone 14 kinds of organic solvents in headspace capillary GC Simultaneously test cefoperazone sodium sulbactam sodium.The people such as Huang Niantao measure multiple Determination of Residual Organic Solvents in Cefotaxime Sodium in HS-SPME-GC method, Chinese Medicine guide 2012,10 (16), provide in 77-79 and utilize Headspace SPME-GC, methyl alcohol, ethanol, acetone, isobutyl alcohol, methylene chloride, tetrahydrofuran, ethyl acetate and dimethyl acetamide these 8 kinds of solvents in Simultaneously test Cefotaxime Sodium.Residual solvent-methyl alcohol, ethanol, acetone, methylene chloride, the tetrahydrofuran of the people such as Zhang Hongmei in Headspace Gas Chromatography Cefotaxime Sodium, Heilungkiang scientific and technical information, 2008,14, mention in 203-203, utilize these 5 kinds of Determination of Residual Organic Solvents of the methyl alcohol in headspace gas chromatography Simultaneously test Cefotaxime Sodium, ethanol, acetone, methylene chloride, tetrahydrofuran.The people such as Chen Fei organic solvent residual in Headspace Gas Chromatography Ceftriaxone Sodium, Fujian analytical test, 2010, Vol19(3), report in 49-52, by setting up headspace gas chromatography, measure these 7 kinds of organic solvents of methyl alcohol, ethanol, acetonitrile, acetone, isopropyl alcohol, methylene chloride and ethyl acetate residual in ceftriaxone sodium sample.The mensuration of the people such as Zhang Hongmei triethylamine in Cefotaxime Sodium, Heilungkiang medicine, 2003,16(5) in mention, the triethylamine content in Cefotaxime Sodium with gas chromatography determination.
The method detecting organic solvent residual due to gas chromatographic analysis has specificity, and the organic solvent detection method described in above-mentioned document can only detect the solvent mentioned in its document and remain, and cannot detect the organic solvent do not mentioned in other documents simultaneously.
Summary of the invention
The object of the invention is to: provide a kind of method simultaneously detecting multiple residual solvent in Ceftriaxone Sodium, to overcome the defect that existing organic solvent detection method cannot satisfy the demands.
The invention provides a kind of method simultaneously detecting multiple residual solvent in Ceftriaxone Sodium, adopt gas chromatography analysis method, it is characterized in that: methyl alcohol, ethanol, acetonitrile, acetone, ethyl acetate and triethylamine six kinds of organic solvents in detection of drugs simultaneously, in the steps below sequentially:
One, chromatographic condition
Chromatographic column: the capillary column that 100% dimethyl silicone polymer (or polarity is similar) is immobile liquid;
Carrier gas: N
2;
Ascending order heats up: 40 DEG C keep 4-7min, with the ramp to 150 DEG C of 20 DEG C/min, keeps 5-8min;
Injector temperature is 200 DEG C;
Split ratio: 1:1;
Detecting device: flame ionization ditector;
Detector temperature is 250 DEG C;
Head space equilibrium temperature: 60 ~ 70 DEG C;
Head space equilibration time: 30min.
Step 2, reference substance solution and need testing solution to be measured:
1), the preparation of reference substance storing solution:
Precision takes methyl alcohol, ethanol, acetonitrile, acetone, ethyl acetate and triethylamine, puts in volumetric flask, adds dimethyl sulfoxide (DMSO) (DMSO) and dissolves and be diluted to scale, shake up, in contrast product storing solution A;
Precision measures appropriate reference substance storing solution A, puts in measuring bottle, is diluted to scale with DMSO, shake up, in contrast product storing solution B;
2), the preparation of reference substance solution
Get testing sample, accurately weighed, put in 10mL ml headspace bottle, add reference substance storing solution B2mL, sealing, product solution in contrast;
3), the preparation of need testing solution to be measured:
Get testing sample Ceftriaxone Sodium, accurately weighed, put in 10mL ml headspace bottle, add DMSO2mL, sealing, as need testing solution to be measured;
Step 3, carry out system suitability:
Precision measures reference substance storing solution B2mL, put in 10mL ml headspace bottle, sealing, as system suitability solution, get this solution headspace sampling, measure by above-mentioned steps one chromatographic condition, record chromatogram, under showing described chromatographic condition, each component is all separated, and blank solvent is noiseless, goes out peak order and is followed successively by: methyl alcohol, ethanol, acetonitrile, acetone, ethyl acetate, triethylamine;
Step 4, quantitative limit:
Get proper amount of methanol, ethanol, acetonitrile, acetone, ethyl acetate, triethylamine respectively, accurately weighed, dissolve with DMSO and make the suitable solution of concentration, measuring under described chromatographic condition, limit with S/N=10 calculation in quantity;
Step 5, linearity and range:
Get within the scope of reference substance storing solution A0.1 ~ 1.0mL, by volume gradient precision measures many parts, is placed in the equal-volume volumetric flask with storing solution A equal parts respectively, is diluted to scale, shakes up with DMSO, for subsequent use; Precision measures above-mentioned each solution 2mL, is placed in the 10mL ml headspace bottle that appropriate testing sample is housed, and sealing obtains the application of sample solution of multiple concentration; The parallel preparation of each concentration 2 parts; Get above-mentioned solution headspace sampling respectively, measure by described chromatographic condition, record chromatogram, does linear regression with peak area A to concentration C (mg/mL), obtains equation of linear regression and the related coefficient of each component;
Step 6, the recovery:
In the variable concentrations application of sample solution obtained in step 5, by volume gradient is appointed and is taken to few three variable concentrations application of sample solution, the parallel preparation of each concentration 3 parts, gets described solution and need testing solution headspace sampling respectively, measure by described chromatographic condition, record chromatogram;
Step 7, residual solvent measure:
Precision measures need testing solution and reference substance solution headspace sampling respectively, and record chromatogram, by standard addition method with methyl alcohol, ethanol, acetonitrile, acetone, ethyl acetate, triethylamine content in calculated by peak area test article.
The invention has the advantages that, one, adopt vapor-phase chromatography to detect the content of methyl alcohol, ethanol, acetonitrile, acetone, ethyl acetate, triethylamine 6 kinds of organic solvents, highly sensitive, reproducible, degree of accuracy is high simultaneously.
Two, use standard addition method, do not need other standard substance to make internal standard compound, only need predict the pure material of component, can matrix effect be offset, simple to operate.
Three, the present invention adopts headspace injection method, avoids direct solution example to the interference detected and the pollution come chromatogram cornice.
Four, adopt temperature programme method, can effectively be separated low boiling and high boiling organic solvent.
Accompanying drawing explanation
Fig. 1 reference substance storing solution B spectrogram, carry out system suitability, precision measures reference substance storing solution B2mL, puts in 10mL ml headspace bottle, sealing, as system suitability solution, get this solution headspace sampling, measure by described chromatographic condition, record chromatogram, under described chromatographic condition, each component is all separated, and blank solvent is noiseless, goes out peak and is followed successively by according to time sequencing: methyl alcohol, ethanol, acetonitrile, acetone, ethyl acetate, triethylamine;
Fig. 2 is methyl alcohol quantitative limit spectrogram, gets proper amount of methanol DMSO and dissolves and make the suitable solution of concentration, measure, calculate methyl alcohol quantitative limit with S/N=10 under described chromatographic condition;
Fig. 3 is ethanol quantitative limit spectrogram;
Fig. 4 is acetonitrile quantitative limit spectrogram;
Fig. 5 is acetone quantitative limit spectrogram;
Fig. 6 is ethyl acetate quantitative limit spectrogram;
Fig. 7 is triethylamine spectrogram;
Fig. 8 is linear 1 spectrogram, is reference substance storing solution A0.1mL/0.1g testing sample;
Linearity and range: by volume gradient precision measure reference substance storing solution A0.1,0.2,0.4,0.5,0.6,0.8,1.0mL, be placed in 10mL measuring bottle respectively, be diluted to 10mL scale with DMSO, shake up, for subsequent use; Precision measures above-mentioned each solution 2mL, is placed in the 10mL ml headspace bottle that 0.1g testing sample is housed, sealing, the parallel preparation of each concentration 2 parts; Get above-mentioned solution headspace sampling respectively, measure by described chromatographic condition, record chromatogram, does linear regression with peak area A to concentration C (mg/mL), obtains equation of linear regression and the related coefficient of each component;
Fig. 9 is linear 2 spectrograms, is reference substance storing solution A0.2mL/0.1g testing sample;
Figure 10 is linear 3 spectrograms, is reference substance storing solution A0.4mL/0.1g testing sample;
Figure 11 is linear 4 spectrograms, is reference substance storing solution A0.5mL/0.1g testing sample;
Figure 12 is linear 5 spectrograms, is reference substance storing solution A0.6mL/0.1g testing sample;
Figure 13 is linear 6 spectrograms, is reference substance storing solution A0.8mL/0.1g testing sample;
Figure 14 is linear 7 spectrograms, is reference substance storing solution A1.0mL/0.1g testing sample;
Figure 15 is residual solvent spectrogram in ceftriaxone sodium sample.
Embodiment
1 instrument and reagent
Agilent6890N gas chromatograph; Agilent7694E head-space sampler; Ceftriaxone Sodium (lot number: TQ0043); DMSO is HPLC level, and it is pure that all the other reagent are analysis.
2 chromatographic conditions
Chromatographic column: 100% dimethyl silicone polymer is the capillary column (HP-160m × 530 μm × 5.00 μm) of immobile liquid;
Carrier gas: N
2;
Ascending order heats up: 40 DEG C keep 4min, with 20 DEG C ˙ min
-1ramp to 150 DEG C, keep 6min;
Injector temperature is 200 DEG C (split ratio: 1:1, column cap pressure 7.70psi);
Detecting device: flame ionization ditector (FID);
Detector temperature: 250 DEG C;
Head space equilibrium temperature: 60 DEG C;
Head space equilibration time: 30min;
Take DMSO as solvent.
The preparation of 3 solution
The preparation of 3.1 reference substance storing solutions
Precision takes methyl alcohol 0.15g, ethanol 0.25g, acetonitrile 0.0205g, acetone 0.25g, ethyl acetate 0.25g, triethylamine 0.016g, puts in 50mL volumetric flask, adds DMSO and dissolves and be diluted to scale, shake up, in contrast product storing solution A.
Precision measures reference substance storing solution A5mL, puts in 100mL volumetric flask, is diluted to scale with DMSO, shake up, in contrast product storing solution B.
The preparation of 3.2 reference substance solution
Get testing sample 0.1g, accurately weighed, put in 10mL ml headspace bottle, add reference substance storing solution B2mL, sealing, product solution in contrast.
The preparation of 3.3 need testing solutions
Get testing sample 0.1g, accurately weighed, put in 10mL ml headspace bottle, add DMSO2mL, sealing, as need testing solution.
4 system suitabilities
Precision measures reference substance storing solution B2mL, puts in 10mL ml headspace bottle, and sealing, as system suitability solution.Get this solution headspace sampling, measure by above-mentioned chromatographic condition, record chromatogram, goes out peak order and is followed successively by: methyl alcohol, ethanol, acetonitrile, acetone, ethyl acetate, triethylamine.Under above-mentioned chromatographic condition, each component all can be separated preferably, and blank solvent is noiseless, and each component retention time and degree of separation are in table 1, and chromatogram is shown in Fig. 1.
5 quantitative limit
Get methyl alcohol, ethanol, acetonitrile, acetone, ethyl acetate and triethylamine respectively appropriate, accurately weighed, dissolve with DMSO and make the suitable solution of concentration, measuring under above-mentioned chromatographic condition, with S/N=10 calculation in quantity limit, the results are shown in Table 2, chromatogram is shown in Fig. 2-7.
6 linearity and ranges
Precision measure reference substance storing solution A0.1,0.2,0.4,0.5,0.6,0.8,1.0mL, be placed in 10mL measuring bottle respectively, be diluted to scale with DMSO, shake up, for subsequent use.Precision measures above-mentioned each solution 2mL, is placed in the 10mL ml headspace bottle that 0.1g testing sample is housed, sealing, the parallel preparation of each concentration 2 parts.Get above-mentioned solution headspace sampling, measure by above-mentioned chromatographic condition, record chromatogram, chromatogram is shown in accompanying drawing 8-14.Do linear regression with peak area A to concentration C (mg/mL), the data of the equation of linear regression and related coefficient that obtain each component are in table 3.Test findings shows in corresponding concentration range, the peak area of each component and the good linear relationship of its concentration journey.
7 recovery
Precision measure reference substance storing solution A0.4,0.5,0.6mL, be placed in 10mL measuring bottle respectively, be diluted to scale with DMSO, shake up, for subsequent use.Precision measures above-mentioned each solution 2mL, is placed in the 10mL ml headspace bottle that 0.1g testing sample is housed, and sealing, obtains the application of sample solution of 3 concentration.The parallel preparation of each concentration 3 parts.Get above-mentioned application of sample solution and need testing solution headspace sampling, measure by above-mentioned chromatographic condition, record chromatogram, the results are shown in Table 4-9.Result shows that the accuracy of the method is good.
8 residual solvent measurement results
Precision measures ceftriaxone sodium need testing solution and reference substance solution headspace sampling respectively, and record chromatogram, chromatogram is shown in accompanying drawing 15.Be respectively by appearance time and order: acetone and triethylamine.By standard addition method with calculated by peak area, Ceftriaxone Sodium residual solvent measurement result is in table 10:
。
Claims (3)
1. one kind is detected the method for multiple residual solvent in Ceftriaxone Sodium simultaneously, adopt gas chromatography analysis method, it is characterized in that: methyl alcohol, ethanol, acetonitrile, acetone, ethyl acetate and triethylamine six kinds of organic solvents in detection of drugs simultaneously, in the steps below sequentially:
Step one, selected chromatographic condition,
Chromatographic column: 100% dimethyl silicone polymer is the capillary column of immobile liquid;
Carrier gas: N
2;
Ascending order heats up: 40 DEG C keep 4-7min, with the ramp to 150 DEG C of 20 DEG C/min, keeps 5-8min;
Injector temperature is 200 DEG C;
Split ratio: 1:1;
Detecting device: flame ionization ditector;
Detector temperature is 250 DEG C;
Head space equilibrium temperature: 60 ~ 70 DEG C;
Head space equilibration time: 30min;
Step 2, preparation reference substance solution and need testing solution to be measured,
1), the preparation of reference substance storing solution:
Precision takes methyl alcohol, ethanol, acetonitrile, acetone, ethyl acetate and triethylamine, puts in volumetric flask, adds dmso solution and is diluted to scale, shaking up, in contrast product storing solution A;
Precision measures appropriate reference substance storing solution A, puts in measuring bottle, is diluted to scale with dimethyl sulfoxide (DMSO), shake up, in contrast product storing solution B;
2), the preparation of reference substance solution
Get testing sample, accurately weighed, put in 10mL ml headspace bottle, add reference substance storing solution B2mL, sealing, product solution in contrast;
3), the preparation of need testing solution to be measured:
Get testing sample Ceftriaxone Sodium, accurately weighed, put in 10mL ml headspace bottle, add dimethyl sulfoxide (DMSO) 2mL, sealing, as need testing solution;
Step 3, carry out system suitability:
Precision measures reference substance storing solution B2mL, put in 10mL ml headspace bottle, sealing, as system suitability solution, get this solution headspace sampling, measure by the chromatographic condition of described step one, record chromatogram, show each component to be all separated, blank solvent is noiseless, goes out peak order and is followed successively by: methyl alcohol, ethanol, acetonitrile, acetone, ethyl acetate, triethylamine;
Step 4, quantitative limit:
Get proper amount of methanol, ethanol, acetonitrile, acetone, ethyl acetate, triethylamine respectively, accurately weighed, make the suitable solution of concentration with dmso solution, measure under described chromatographic condition, limit with S/N=10 calculation in quantity;
Step 5, linearity and range:
Get within the scope of reference substance storing solution A0.1 ~ 1.0mL, by volume gradient precision measures many parts, is placed in the equal-volume volumetric flask with storing solution A equal parts respectively, is diluted to volume scale, shakes up with DMSO, for subsequent use; Precision measures above-mentioned each solution 2mL, is placed in the 10mL ml headspace bottle that appropriate testing sample is housed, and sealing obtains the application of sample solution of multiple concentration; The parallel preparation of each concentration 2 parts; Get above-mentioned solution headspace sampling respectively, measure by described chromatographic condition, record chromatogram, does linear regression with peak area A to concentration C mg/mL, obtains equation of linear regression and the related coefficient of each component;
Step 6, the recovery:
In the variable concentrations application of sample solution obtained in step 5, appoint and be taken to few three variable concentrations application of sample solution, the parallel preparation of each concentration 3 parts, get described solution and need testing solution headspace sampling respectively, measure by described chromatographic condition, record chromatogram;
Step 7, residual solvent measure:
Precision measures need testing solution and reference substance solution headspace sampling respectively, and record chromatogram, by standard addition method with methyl alcohol, ethanol, acetonitrile, acetone, ethyl acetate, triethylamine content in calculated by peak area test article.
2. a kind of method simultaneously detecting multiple residual solvent in Ceftriaxone Sodium according to claim 1, is characterized in that: in described step 2:
1) preparation of reference substance storing solution:
Precision takes methyl alcohol 0.15g, ethanol 0.25g, acetonitrile 0.0205g, acetone 0.25g, ethyl acetate 0.25g, triethylamine 0.016g, puts in 50mL volumetric flask, adds dmso solution and is diluted to scale, shaking up, in contrast product storing solution A;
Precision measures reference substance storing solution A5mL, puts in 100mL volumetric flask, is diluted to scale with dimethyl sulfoxide (DMSO), shake up, in contrast product storing solution B;
2) preparation of reference substance solution:
Get testing sample 0.1g, accurately weighed, put in 10mL ml headspace bottle, add reference substance storing solution B2mL, sealing, product solution in contrast;
3) preparation of need testing solution:
Get testing sample 0.1g, accurately weighed, put in 10mL ml headspace bottle, add dimethyl sulfoxide (DMSO) 2mL, sealing, as need testing solution.
3. a kind of method simultaneously detecting multiple residual solvent in Ceftriaxone Sodium according to claim 1, it is characterized in that: in described step 5: the 10mL ml headspace bottle of appropriate testing sample is equipped with in described being placed in, for being placed in the 10mL ml headspace bottle that 0.1g testing sample is housed.
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