CN104133019B - A kind of method detecting diazabicyclo nonane enantiomter - Google Patents
A kind of method detecting diazabicyclo nonane enantiomter Download PDFInfo
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- CN104133019B CN104133019B CN201410394709.4A CN201410394709A CN104133019B CN 104133019 B CN104133019 B CN 104133019B CN 201410394709 A CN201410394709 A CN 201410394709A CN 104133019 B CN104133019 B CN 104133019B
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Abstract
The invention belongs to medical art, the invention discloses one (S, S)-2,8-diazabicyclo [4.3.0] nonane and enantiomter Analyze & separate assay method thereof, the method utilizes column front derivation high performance liquid chromatography, adopts amylose-three (3,5-xylyl carbamate) silica gel is filling agent (AD-H, CHIRALPAK) chiral chromatographic column, with normal hexane-low-alcohol solution for mobile phase, can quantitative measurement (S, S) content of-2,8-diazabicyclos [4.3.0] nonane enantiomter.The inventive method specificity is strong, and accuracy is high.The HPLC figure that Fig. 1 is the content of mensuration (S, S)-2,8-diazabicyclo [4.3.0] nonane enantiomter.
Description
Technical field
The invention belongs to medical art, be specifically related to a kind of method of detection (S, S)-2,8-diazabicyclo [4.3.0] nonane enantiomter.
Background technology
(S, S)-2,8-diazabicyclo [4.3.0] nonane be the synthesis conventional intermediate of carbostyril family antibacterial drugs or initiation material, its molecular formula is C7H14N2, and structural formula is
Containing 2 chiral centers in this molecule, there are 4 optical isomers in theory, but what most possibly exist in conjunction with its synthetic method and reaction mechanism analysis only has enantiomter, i.e. (R, R)-2,8-diazabicyclos [4.3.0] nonane, this impurity is by subsequent reactions, remain in QNS, affect drug quality.Therefore control the content of (S, S)-2,8-enantiomter in diazabicyclo [4.3.0] nonane, to improve QNS quality, ensure that the security of extensive patients medication is significant.
For (S, S)-2,8-enantiomter impurity of diazabicyclo [4.3.0] nonane, need to carry out quality control in the middle of pharmaceutical synthesis process.Containing the difficult point that the separation of the optical isomer of asymmetric carbon atom is quality control in pharmaceutical synthesis and production process always, by literature search, (S, S)-2,8-report of diazabicyclo [4.3.0] nonane enantiomerism body detecting method is had no.
Summary of the invention
The object of the present invention is to provide a kind of Analyze & separate (S, S)-2, the column front derivation high performance liquid chromatography of 8-diazabicyclo [4.3.0] nonane and enantiomter impurity thereof, thus realize (S, S) separation determination of-2,8-diazabicyclos [4.3.0] nonane and enantiomter impurity thereof.
Inventor finds, with amylose-three (3,5-xylyl carbamate) silica gel is the chiral chromatographic column of filling agent, with normal hexane-lower alcohol-amine solvent mixed solution for mobile phase, can by (S, S)-2,8-diazabicyclo [4.3.0] nonane and enantiomter thereof are effectively separated, thus accurately can control (S, S)-2,8-quality of diazabicyclo [4.3.0] nonane.
Further, be first the chiral chromatographic column AD-H (CHIRALPAK, 250 × 4.6mm, 5 μm) of filling agent in order to amylose-three (3,5-xylyl carbamate) silica gel, better Analyze & separate effect can be obtained.
Further, normal hexane-lower alcohol-amine solvent mixed solution of the present invention is the mixed solution of normal hexane-absolute ethyl alcohol-triethylamine.
It is (55 ~ 75) ︰ (25 ~ 45) ︰ (0.05 ~ 1) that mobile phase in method of the present invention selects volume ratio to be the volume ratio of normal hexane-absolute ethyl alcohol-triethylamine.The volume ratio of preferred normal hexane-absolute ethyl alcohol-triethylamine is 65 ︰ 35 ︰ 0.1.
Analyze & separate method of the present invention, can realize in accordance with the following methods:
(1) get o-fluoronitrobenzene 0.84 ~ 1.26ml and be placed in 25ml measuring bottle, dissolve with 10ml methylene chloride, precision adds triethylamine 1.65 ~ 2.47ml, as solution A; Getting SS configuration sample 0.5 ~ 0.75g puts in 25ml measuring bottle, dissolves, as solution B with methylene chloride 10ml; Solution B added in solution A, and be settled to scale with methylene chloride, water-bath 25 ~ 35 DEG C heating 60 ~ 90min, as solution C; Precision measures solution C 0.2 ~ 0.4ml, is placed in 25ml measuring bottle, is diluted to scale with absolute ethyl alcohol, as need testing solution;
(2) arranging flow rate of mobile phase is 0.4 ~ 0.6ml/min, and determined wavelength is 246nm, and chromatographic column column oven is 25 ~ 35 DEG C;
(3) get sample solution 10 ~ 30 μ l injection liquid chromatography of step (1), complete (S, S)-2,8-diazabicyclo [4.3.0] nonane and enantiomter thereof analysis be separated.
Wherein:
Chromatographic column: the chiral chromatographic column AD-H (CHIRALPAK, 250 × 4.6mm, 5 μm) taking amylose-three (3,5-xylyl carbamate) silica gel as filling agent;
Mobile phase: normal hexane-absolute ethyl alcohol-triethylamine=65 ︰ 35 ︰ 0.1;
Column temperature: 30 DEG C;
Determined wavelength: 246nm;
Flow velocity: 0.5ml/min;
Sampling volume: 20 μ l.
The present invention adopts AD-H (CHIRALPAK, 250 × 4.6mm, 5 μm), with amylose-three (3,5-xylyl carbamate) silica gel is the chiral chromatographic column of filling agent, can effectively Analyze & separate (S, S)-2,8-diazabicyclo [4.3.0] nonane and enantiomter (impurity) thereof.The invention solves containing (S, S)-2, the analysis of the raw material of 8-diazabicyclo [4.3.0] nonane and enantiomter thereof and separation problem thus ensure that (S, S)-2,8-diazabicyclo [4.3.0] nonane quality controllable.
Accompanying drawing explanation
Fig. 1: normal hexane-absolute ethyl alcohol-triethylamine=65 ︰ 35 ︰ 0.1, the HPLC figure that column temperature is 30 DEG C:
In figure, chromatographic peak 1 is isomeride (R, R)-2,8-diazabicyclo [4.3.0] nonane, and chromatographic peak 2 is (S, S)-2,8-diazabicyclo [4.3.0] nonane.
Fig. 2: normal hexane-absolute ethyl alcohol-triethylamine=65 ︰ 35 ︰ 0.1, the HPLC figure that column temperature is 35 DEG C:
In figure, chromatographic peak 1 is isomeride (R, R)-2,8-diazabicyclo [4.3.0] nonane, and chromatographic peak 2 is (S, S)-2,8-diazabicyclo [4.3.0] nonane.
Fig. 3: normal hexane-absolute ethyl alcohol-triethylamine=65 ︰ 35 ︰ 0.1, the HPLC figure that column temperature is 25 DEG C:
In figure, chromatographic peak 1 is isomeride (R, R)-2,8-diazabicyclo [4.3.0] nonane, and chromatographic peak 2 is (S, S)-2,8-diazabicyclo [4.3.0] nonane.
Fig. 4: normal hexane-absolute ethyl alcohol-triethylamine=70 ︰ 30 ︰ 0.2, the HPLC figure that column temperature is 35 DEG C:
In figure, chromatographic peak 1 is isomeride (R, R)-2,8-diazabicyclo [4.3.0] nonane, and chromatographic peak 2 is (S, S)-2,8-diazabicyclo [4.3.0] nonane.
Fig. 5: normal hexane-absolute ethyl alcohol-triethylamine=60 ︰ 40 ︰ 0.2, the HPLC figure that column temperature is 35 DEG C:
In figure, chromatographic peak 1 is isomeride (R, R)-2,8-diazabicyclo [4.3.0] nonane, and chromatographic peak 2 is (S, S)-2,8-diazabicyclo [4.3.0] nonane.
Embodiment
Embodiment 1
Instrument and condition
Mobile phase: normal hexane-absolute ethyl alcohol-triethylamine=65 ︰ 35 ︰ 0.1;
Column temperature: 30 DEG C;
Determined wavelength: 246nm;
Flow velocity: 0.5ml/min;
Sampling volume: 20 μ l.
Test procedure:
Get o-fluoronitrobenzene 1.0ml and be placed in 25ml measuring bottle, dissolve with 10ml methylene chloride, precision adds triethylamine 1.65ml, as solution A; Getting SS configuration sample 0.5g puts in 25ml measuring bottle, dissolves, as solution B with methylene chloride 10ml; Solution B added in solution A, and be settled to scale with methylene chloride, water-bath 25 DEG C heating 60min, as solution C; Precision measures solution C 0.2ml, is placed in 25ml measuring bottle, is diluted to scale with ethanol, as need testing solution.Get RR configuration standard items 7.5mg, be made in the same way of reference substance solution.Precision measures above-mentioned need testing solution and each 20 μ l of reference substance solution, measures according to above-mentioned high-efficient liquid phase chromatogram condition, and record chromatogram, by external standard method with the calculated by peak area isomery scale of construction.
The results are shown in accompanying drawing 1, in figure, chromatographic peak 1 is isomeride (R, R)-2,8-diazabicyclo [4.3.0] nonane, chromatographic peak 2 is (S, S)-2,8-diazabicyclo [4.3.0] nonane, can find out (S, S)-2 under this condition, 8-diazabicyclo [4.3.0] nonane and isomeride (R, R)-2,8-diazabicyclos [4.3.0] nonane peak is separated completely, and (S, S)-2,8-diazabicyclos [4.3.0] nonane peak is at about 30.918min.
Embodiment 2
Instrument and condition
Mobile phase: normal hexane-absolute ethyl alcohol-triethylamine=65 ︰ 35 ︰ 0.1;
Column temperature: 35 DEG C;
Determined wavelength: 246nm;
Flow velocity: 0.5ml/min;
Sampling volume: 20 μ l.
Test procedure:
Get o-fluoronitrobenzene 1.0ml and be placed in 25ml measuring bottle, dissolve with 10ml methylene chloride, precision adds triethylamine 1.65ml, as solution A; Getting SS configuration sample 0.5g puts in 25ml measuring bottle, dissolves, as solution B with methylene chloride 10ml; Solution B added in solution A, and be settled to scale with methylene chloride, water-bath 25 DEG C heating 60min, as solution C; Precision measures solution C 0.2ml, is placed in 25ml measuring bottle, is diluted to scale with ethanol, as need testing solution.Get RR configuration standard items 7.5mg, be made in the same way of reference substance solution.Precision measures above-mentioned need testing solution and each 20 μ l of reference substance solution, measures according to above-mentioned high-efficient liquid phase chromatogram condition, and record chromatogram, by external standard method with the calculated by peak area isomery scale of construction.
The results are shown in accompanying drawing 2, in figure, chromatographic peak 1 is isomeride (R, R)-2,8-diazabicyclo [4.3.0] nonane, chromatographic peak 2 is (S, S)-2,8-diazabicyclo [4.3.0] nonane, can find out (S, S)-2 under this condition, 8-diazabicyclo [4.3.0] nonane and isomeride (R, R)-2,8-diazabicyclos [4.3.0] nonane peak is separated completely, and (S, S)-2,8-diazabicyclos [4.3.0] nonane peak is at about 30.302min.
Embodiment 3
Instrument and condition
Mobile phase: normal hexane-absolute ethyl alcohol-triethylamine=65 ︰ 35 ︰ 0.1;
Column temperature: 25 DEG C;
Determined wavelength: 246nm;
Flow velocity: 0.5ml/min;
Sampling volume: 20 μ l.
Test procedure:
Get o-fluoronitrobenzene 1.0ml and be placed in 25ml measuring bottle, dissolve with 10ml methylene chloride, precision adds triethylamine 1.65ml, as solution A; Getting SS configuration sample 0.5g puts in 25ml measuring bottle, dissolves, as solution B with methylene chloride 10ml; Solution B added in solution A, and be settled to scale with methylene chloride, water-bath 25 DEG C heating 60min, as solution C; Precision measures solution C 0.2ml, is placed in 25ml measuring bottle, is diluted to scale with ethanol, as need testing solution.Get RR configuration standard items 7.5mg, be made in the same way of reference substance solution.Precision measures above-mentioned need testing solution and each 20 μ l of reference substance solution, measures according to above-mentioned high-efficient liquid phase chromatogram condition, and record chromatogram, by external standard method with the calculated by peak area isomery scale of construction.
The results are shown in accompanying drawing 3, in figure, chromatographic peak 1 is isomeride (R, R)-2,8-diazabicyclo [4.3.0] nonane, chromatographic peak 2 is (S, S)-2,8-diazabicyclo [4.3.0] nonane, can find out (S, S)-2 under this condition, 8-diazabicyclo [4.3.0] nonane and isomeride (R, R)-2,8-diazabicyclos [4.3.0] nonane peak is separated completely, and (S, S)-2,8-diazabicyclos [4.3.0] nonane peak is at about 31.365min.
Embodiment 4
Instrument and condition
Mobile phase: normal hexane-absolute ethyl alcohol-triethylamine=70 ︰ 30 ︰ 0.2;
Column temperature: 30 DEG C;
Determined wavelength: 246nm;
Flow velocity: 0.5ml/min;
Sampling volume: 20 μ l.
Test procedure:
Get o-fluoronitrobenzene 0.84ml and be placed in 25ml measuring bottle, dissolve with 10ml methylene chloride, precision adds triethylamine 1.65ml, as solution A; Getting SS configuration sample 0.5g puts in 25ml measuring bottle, dissolves, as solution B with methylene chloride 10ml; Solution B added in solution A, and be settled to scale with methylene chloride, water-bath 25 DEG C heating 60min, as solution C; Precision measures solution C 0.2ml, is placed in 25ml measuring bottle, is diluted to scale with ethanol, as need testing solution.Get RR configuration standard items 7.5mg, be made in the same way of reference substance solution.Precision measures above-mentioned need testing solution and each 20 μ l of reference substance solution, measures according to above-mentioned high-efficient liquid phase chromatogram condition, and record chromatogram, by external standard method with the calculated by peak area isomery scale of construction.
The results are shown in accompanying drawing 4, in figure, chromatographic peak 1 is isomeride (R, R)-2,8-diazabicyclo [4.3.0] nonane, chromatographic peak 2 is (S, S)-2,8-diazabicyclo [4.3.0] nonane, can find out (S, S)-2 under this condition, 8-diazabicyclo [4.3.0] nonane and isomeride (R, R)-2,8-diazabicyclos [4.3.0] nonane peak is separated completely, and (S, S)-2,8-diazabicyclos [4.3.0] nonane peak is at about 29.883min.
Embodiment 5
Instrument and condition
Mobile phase: normal hexane-absolute ethyl alcohol-triethylamine=60 ︰ 40 ︰ 0.2;
Column temperature: 30 DEG C;
Determined wavelength: 246nm;
Flow velocity: 0.5ml/min;
Sampling volume: 20 μ l.
Test procedure:
Get o-fluoronitrobenzene 0.84ml and be placed in 25ml measuring bottle, dissolve with 10ml methylene chloride, precision adds triethylamine 1.65ml, as solution A; Getting SS configuration sample 0.5g puts in 25ml measuring bottle, dissolves, as solution B with methylene chloride 10ml; Solution B added in solution A, and be settled to scale with methylene chloride, water-bath 25 DEG C heating 60min, as solution C; Precision measures solution C 0.2ml, is placed in 25ml measuring bottle, is diluted to scale with ethanol, as need testing solution.Get RR configuration standard items 7.5mg, be made in the same way of reference substance solution.Precision measures above-mentioned need testing solution and each 20 μ l of reference substance solution, measures according to above-mentioned high-efficient liquid phase chromatogram condition, and record chromatogram, by external standard method with the calculated by peak area isomery scale of construction.
The results are shown in accompanying drawing 5, in figure, chromatographic peak 1 is isomeride (R, R)-2,8-diazabicyclo [4.3.0] nonane, chromatographic peak 2 is (S, S)-2,8-diazabicyclo [4.3.0] nonane, can find out (S, S)-2 under this condition, 8-diazabicyclo [4.3.0] nonane and isomeride (R, R)-2,8-diazabicyclos [4.3.0] nonane peak is separated completely, and (S, S)-2,8-diazabicyclos [4.3.0] nonane peak is at about 31.847min.
Claims (1)
1. a column front derivation high performance liquid chromatography is separated (S, S)-2, the method of 8-diazabicyclo [4.3.0] nonane enantiomter, it is characterized in that: adopt with amylose-three (3,5-xylyl carbamate) silica gel is the chiral chromatographic column of filling agent, with normal hexane-lower alcohol-amine solvent mixed solution for mobile phase; The mixed solution of described mixed solution to be normal hexane-absolute ethyl alcohol-triethylamine be by volume 65 ︰ 35 ︰ 0.1; Described chiral chromatographic column selects AD-H, CHIRALPAK, 250 × 4.6mm, 5 μm; Said method comprising the steps of:
(1) get o-fluoronitrobenzene 0.84 ~ 1.26ml and be placed in 25ml measuring bottle, dissolve with 10ml methylene chloride, precision adds triethylamine 1.65 ~ 2.47ml, as solution A; Getting SS configuration sample 0.5 ~ 0.75g puts in 25ml measuring bottle, dissolves, as solution B with methylene chloride 10ml; Solution B added in solution A, and be settled to scale with methylene chloride, water-bath 25 ~ 35 DEG C heating 60 ~ 90min, as solution C; Precision measures solution C 0.2 ~ 0.4ml, is placed in 25ml measuring bottle, is diluted to scale with absolute ethyl alcohol, as need testing solution;
(2) arranging flow rate of mobile phase is 0.4 ~ 0.6ml/min, and determined wavelength is 246nm, and chromatographic column column oven is 25 ~ 35 DEG C;
(3) sample solution 10 ~ 30 μ l injection liquid chromatography of step (1) is got, record chromatogram.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102952130A (en) * | 2011-08-24 | 2013-03-06 | 重庆华邦胜凯制药有限公司 | Method for chiral synthesis of (S,S)-2-8-diazabicyclononane |
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| US7741513B2 (en) * | 2008-01-16 | 2010-06-22 | Richman Jack E | Thioacids and thioacid salts for determining the enantiomeric excess of chiral compounds containing an electrophilic carbon center |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102952130A (en) * | 2011-08-24 | 2013-03-06 | 重庆华邦胜凯制药有限公司 | Method for chiral synthesis of (S,S)-2-8-diazabicyclononane |
Non-Patent Citations (4)
| Title |
|---|
| (．筇)．2,8．二氮杂双环[4．3．0]壬烷的合成;张明光等;《中国医药工业杂志》;20121231;第43卷(第8期);第658-661页 * |
| Enantiomeric separation of a moxifloxacin intermediate by chiral liquid chromatography using cellulose based stationary phases;T. Radhakrishna et al.;《Journal of Pharmaceutical and Biomedical Analysis》;20001231;第22卷;第691页右栏第3段至第692页左栏第1段、第693-696页第2.2、2.4-3部分 * |
| Structural identification and characterization of impurities in moxifloxacin;Y. Ravindra Kumar et al.;《Journal of Pharmaceutical and Biomedical Analysis》;20041231;第34卷;第1125-1129页 * |
| 柱前衍生高效液相色谱法分离分析1-氮杂双环[ 2 , 2 , 2] 辛-3-基胺对映异构体;邓婕等;《分析化学》;20061031;第34卷(第10期);第1475-1478页 * |
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