CN116465985A - Method for detecting residual solvent in alpha-ribose mesylate by gas chromatography - Google Patents
Method for detecting residual solvent in alpha-ribose mesylate by gas chromatography Download PDFInfo
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- CN116465985A CN116465985A CN202310195703.3A CN202310195703A CN116465985A CN 116465985 A CN116465985 A CN 116465985A CN 202310195703 A CN202310195703 A CN 202310195703A CN 116465985 A CN116465985 A CN 116465985A
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- -1 alpha-ribose mesylate Chemical compound 0.000 title claims abstract description 20
- 239000013557 residual solvent Substances 0.000 title claims abstract description 20
- 238000000034 method Methods 0.000 title claims abstract description 17
- 238000004817 gas chromatography Methods 0.000 title claims abstract description 15
- 238000001514 detection method Methods 0.000 claims abstract description 12
- 238000002347 injection Methods 0.000 claims abstract description 12
- 239000007924 injection Substances 0.000 claims abstract description 12
- 239000002904 solvent Substances 0.000 claims abstract description 11
- 239000012159 carrier gas Substances 0.000 claims abstract description 9
- 238000010438 heat treatment Methods 0.000 claims abstract description 9
- 239000007789 gas Substances 0.000 claims abstract description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 21
- 239000000523 sample Substances 0.000 claims description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 14
- 239000000243 solution Substances 0.000 claims description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- 239000003085 diluting agent Substances 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- IRSJDVYTJUCXRV-UHFFFAOYSA-N ethyl 2-bromo-2,2-difluoroacetate Chemical compound CCOC(=O)C(F)(F)Br IRSJDVYTJUCXRV-UHFFFAOYSA-N 0.000 claims description 6
- 239000011550 stock solution Substances 0.000 claims description 5
- 230000005540 biological transmission Effects 0.000 claims description 4
- 238000007865 diluting Methods 0.000 claims description 4
- 239000013558 reference substance Substances 0.000 claims description 4
- 238000007789 sealing Methods 0.000 claims description 4
- 239000012085 test solution Substances 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 239000012488 sample solution Substances 0.000 claims description 3
- 238000005303 weighing Methods 0.000 claims description 3
- 238000004458 analytical method Methods 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 claims description 2
- 238000010812 external standard method Methods 0.000 claims description 2
- 238000005070 sampling Methods 0.000 claims description 2
- 230000014759 maintenance of location Effects 0.000 claims 2
- 238000002360 preparation method Methods 0.000 claims 2
- 230000035945 sensitivity Effects 0.000 abstract description 4
- 239000000126 substance Substances 0.000 abstract description 2
- 239000010453 quartz Substances 0.000 abstract 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 abstract 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 5
- 239000012490 blank solution Substances 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 238000011084 recovery Methods 0.000 description 3
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 2
- 229960005144 gemcitabine hydrochloride Drugs 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000012088 reference solution Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- YGSFNCRAZOCNDJ-UHFFFAOYSA-N propan-2-one Chemical compound CC(C)=O.CC(C)=O YGSFNCRAZOCNDJ-UHFFFAOYSA-N 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/86—Signal analysis
- G01N30/8675—Evaluation, i.e. decoding of the signal into analytical information
- G01N30/8679—Target compound analysis, i.e. whereby a limited number of peaks is analysed
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Engineering & Computer Science (AREA)
- Library & Information Science (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
Abstract
The invention discloses a method for detecting residual solvent in alpha-ribose mesylate by using gas chromatography, which belongs to the technical field of chemical detection, wherein the residual solvent in the alpha-ribose mesylate is detected by using the gas chromatography, the instrument is a gas chromatograph, the detector is a FID detector, a chromatographic column adopts a DB-WAX quartz capillary chromatographic column, and carrier gas is N 2 The flow rate is 3.0mL/min, the split ratio is 20:1, and the column temperature is as follows: maintaining at 40deg.C for 10 min, heating to 80deg.C at 10deg.C per minute, heating to 250deg.C per minute for 3 min, introducing sample into the headspace, balancing temperature at 90deg.C, quantifying ring temperature at 100deg.C, and transmitting line temperature at 110deg.C for 30min; sample injection volume: 1.0ml, can effectively separate the residual solvent in the alpha-ribose mesylate and quantitatively detect the content of the residual solvent, and the method has the advantages of simple operation, strong specificity, high sensitivity, high accuracy, good linearity and durability, and can accurately and rapidly determine the alpha-room ratioResidual amount of 8 solvents in ribomethane sulfonate.
Description
Technical Field
The invention belongs to the technical field of chemical detection, and particularly relates to a method for detecting residual solvent in alpha-ribose mesylate by using a gas chromatography.
Background
The method has the advantages that alpha-ribose mesylate is an important starting material in the synthesis of gemcitabine hydrochloride bulk drug, gemcitabine hydrochloride is an anticancer drug with wide clinical application, the injection is marketed in a plurality of countries, the quality of the starting material is particularly important to control at the source, no report is made on the detection method of the residual solvent in the alpha-ribose mesylate at present, the organic solvent residue in the alpha-ribose mesylate has a certain influence on the product quality, therefore, the development of a detection method capable of effectively detecting the residual solvent in the alpha-ribose mesylate is necessary, and the method is researched and developed for a long time to detect the residual solvent in the alpha-ribose mesylate, and is convenient to operate and good in detection effect.
Disclosure of Invention
In view of the shortcomings of the prior art, the invention aims to provide a method for detecting residual solvent in alpha-ribose mesylate by gas chromatography, which comprises the following steps:
1) Selection of instrument and chromatographic conditions: a gas chromatograph; the chromatographic column is DB-WAX (30 m×0.53mm×1.0 μm) capillary chromatographic column; adopting an FID detector, wherein the initial temperature of the chromatographic column is 35-45 ℃, the holding time is 8-12min, then the temperature is increased to 80 ℃ at the heating rate of 8-12 ℃/min, and then the final temperature of the chromatographic column is 250 ℃ at the heating rate of 35-45 ℃/min, and the final temperature holding time of the chromatographic column is 2-5min; the carrier gas is nitrogen, the flow rate of the carrier gas is 2.5-3.5ml/min, and the split ratio is 20:1; the temperature of the sample inlet is 190-210 ℃ and the temperature of the detector is 240-260 ℃; the sample injection mode is headspace sample injection, the equilibrium temperature is 90 ℃, the quantitative loop temperature is 100 ℃, the transmission line temperature is 110 ℃, and the equilibrium time is 30min; the sample volume was 1.0mL.
2) Preparing a solution, and preparing the following solutions:
a. blank solution (diluent): dimethyl sulfoxide;
b. control solution: weighing 0.5g of acetone, 0.06g of dichloromethane, 0.072g of tetrahydrofuran, 0.5g of ethyl acetate, 0.089g of toluene, 0.5g of diethyl ether, 0.041g of acetonitrile and 0.1g of ethyl difluorobromoacetate, placing into a 50ml measuring flask, diluting to a scale with a diluent, and shaking uniformly to obtain a stock solution; transferring 2.0ml of stock solution, placing into a 100ml measuring flask, diluting to scale with diluent, shaking, precisely measuring 5.0ml, placing into a 20ml headspace bottle, and sealing with a cover. C. Test solution: taking 0.2g of alpha-ribose mesylate, placing the alpha-ribose mesylate into a 20ml headspace bottle, adding 5.0ml of diluent for dissolution, capping, sealing and shaking uniformly to obtain the finished product, and preparing 2 parts in parallel.
Sampling according to the following sequence table:
| name of the name | Number of sample injection needles |
| Blank solution | 1 or more needle |
| Reference substance solution | 6 needle |
| Test solution | Each needle is inserted into 1 needle |
The peak area of each solvent in the alpha-ribose mesylate test sample solution is calculated by an external standard method.
Preferably, the chromatographic conditions selected for the gas chromatographic analysis according to the invention are as follows:
using a FID detector;
chromatographic column: DB-WAX (30 m x 0.53mm x 1.0 μm) capillary chromatographic column;
programming temperature: the initial temperature was 40℃for 10 minutes, at 10℃per minute to 80℃and at 40℃per minute to 250℃for 3 minutes.
Carrier gas: nitrogen gas flow rate of 3.0mL/min, split ratio: 20:1;
sample inlet temperature: 200 ℃;
detector (FID) temperature: 250 ℃;
sample injection mode: feeding the sample in the headspace, balancing the temperature to 90 ℃, quantifying the ring temperature to 100 ℃, and balancing the transmission line temperature to 110 ℃ for 30min;
sample injection volume: 1.0ml.
The beneficial effects of the invention are as follows:
the method can effectively separate the residual solvent in the alpha-ribose mesylate and quantitatively detect the content of the residual solvent, wherein the residual solvent is one or more than two of diethyl ether, acetone, tetrahydrofuran, ethyl acetate, methylene dichloride, acetonitrile, toluene and ethyl difluorobromoacetate.
Drawings
FIG. 1 is a blank solution chromatogram;
FIG. 2 is a chromatogram of a control solution;
FIG. 3 is a chromatogram of a test solution;
FIG. 4 is a graph of the results of a linear test of each solvent;
FIG. 5 is a chromatogram of an accurate solution.
Detailed Description
The invention will be further illustrated with reference to the above examples (figures), but it should not be understood that the scope of the invention is limited to the following examples.
The instrumentation and chromatographic conditions used in the following examples are as follows:
the gas chromatograph is Agilent7890A, a FID detector is adopted, the initial temperature of the column is 35-45 ℃, the holding time is 8-12min, then the temperature is increased to 80 ℃ at the heating rate of 8-12 ℃/min, the final temperature of the column is 250 ℃ at the heating rate of 35-45 ℃/min, and the final temperature holding time of the column is 2-5min; the carrier gas is nitrogen, preferably, the flow rate of the carrier gas is 2.5-3.5ml/min, and the split ratio is 20:1; the temperature of the sample inlet is 190-210 ℃ and the temperature of the detector is 240-260 ℃; the sample injection mode is headspace sample injection, the equilibrium temperature is 90 ℃, the quantitative loop temperature is 100 ℃, the transmission line temperature is 110 ℃, and the equilibrium time is 30min; the sample volume was 1.0mL.
Example 1
The specificity was examined as shown in fig. 1 to 2 and fig. 5:
precisely measuring 1.0mL of blank solution, reference substance solution and impurity locating solution, injecting into gas chromatograph, and recording chromatogram. The experimental results of the positioning and the separation degree of each impurity show that the method has no interference to the measurement of the sample, the minimum separation degree between the adjacent solvents is 2.60, the specificity of the analysis condition is good, and the test result is as follows:
example 2
Sensitivity test investigation results:
the limit of quantitation (LOQ) results are as follows:
the limit of detection (LOD) results are as follows:
the quantitative limit and the detection limit of each solvent are shown as follows: the detection sensitivity of each solvent is high (far higher than the standard value of the limit), and the method sensitivity meets the requirements.
Example 3
Linearity investigation, as shown in fig. 4:
the peak area is plotted against the concentration, the diethyl ether is in the range of 40.664 μg/mL-304.980 μg/mL, the acetone is in the range of 40.120 μg/mL-300.900 μg/mL, the tetrahydrofuran is in the range of 5.928 μg/mL-44.460 μg/mL, the ethyl acetate is in the range of 40.160 μg/mL-301.200 μg/mL, the dichloromethane is in the range of 5.128 μg/mL-38.460 μg/mL, the acetonitrile is in the range of 3.232 μg/mL-24.240 μg/mL, the toluene is in the range of 7.016 μg/mL-52.620 μg/mL, the ethyl difluorobromoacetate is in the range of 8.792 μg/mL-65.940 μg/mL, the sample concentration is in a linear relationship with the peak area, the linearity is good, and the specific results are as follows:
| name of the name | Linear equation | R 2 |
| Diethyl ether | y＝0.2849x-1.0310 | 0.9993 |
| Acetone (acetone) | y＝0.0526x-0.2046 | 0.9996 |
| Tetrahydrofuran (THF) | y＝0.0698x-0.0407 | 0.9996 |
| Acetic acid ethyl ester | y＝0.0393x-0.1650 | 0.9996 |
| Dichloromethane (dichloromethane) | y＝0.0116x-0.0067 | 0.9995 |
| Acetonitrile | y＝0.0154x-0.0052 | 0.9987 |
| Toluene (toluene) | y＝0.0532x-0.0527 | 0.9994 |
| Difluoro bromoacetic acid ethyl ester | y＝0.0046x-0.0058 | 0.9993 |
Example 4
Accuracy inspection, chromatogram is shown in fig. 5:
preparing recovery rate solutions according to 50%, 100% and 150% of limit concentrations of diethyl ether, acetone, tetrahydrofuran, ethyl acetate, dichloromethane, acetonitrile, toluene and ethyl difluorobromoacetate, preparing 3 parts of each group of concentration in parallel, preparing a sample solution and a reference solution, and calculating recovery rate according to the chromatographic conditions. The recovery rate of each solvent is in the range of 90% -110%, and the results are shown in the following table:
example 5
Durability test, namely, the chromatographic column is replaced, the initial column temperature (40+/-1 ℃), the carrier gas flow rate (3.0+/-0.1 ml/min), the sample inlet temperature (200+/-2 ℃) and the heating rate (+/-1 ℃/min) are changed, RSD of the peak area of each solvent in the reference solution and the minimum separation degree result of each solvent peak are compared, and the durability is tested. Changing chromatographic condition parameters, wherein the maximum RSD of 6 needle peak areas of each solvent in the reference substance solution is 6.7% and less than 10%; the degree of separation of the system applicability solutions is greater than 1.5, which indicates that the method has good durability. The results are shown in the following table:
while the invention has been described with respect to the preferred embodiments thereof, it will be understood by those skilled in the art that various modifications may be made without departing from the principles of the invention, and such modifications should also be considered as being within the scope of the invention and not as being particularly limited thereto.
Claims (5)
1. A method for detecting residual solvent in alpha-ribose mesylate by gas chromatography, comprising the steps of:
1) Selection of instrument and chromatographic conditions: a gas chromatograph; the chromatographic column is DB-WAX (30 m×0.53mm×1.0 μm) capillary chromatographic column; using a FID detector;
1) Preparation of a control solution: weighing 0.5g of acetone, 0.06g of dichloromethane, 0.072g of tetrahydrofuran, 0.5g of ethyl acetate, 0.089g of toluene, 0.5g of diethyl ether, 0.041g of acetonitrile and 0.1g of difluorobromoacetic acid ethyl ester, placing into a 50ml measuring flask, diluting to a scale with a diluent, shaking uniformly to serve as a stock solution, transferring 2.0ml of the stock solution, placing into a 100ml measuring flask, diluting to the scale with the diluent, shaking uniformly, precisely weighing 5.0ml of the stock solution, placing into a 20ml overhead flask, and sealing by capping;
2) Preparation of test solution: taking 0.2g of alpha-ribose mesylate, placing the alpha-ribose mesylate into a 20ml headspace bottle, adding 5.0ml of diluent for dissolution, capping, sealing and shaking uniformly to obtain the finished product;
3) Determination of residual solvent: taking a reference substance solution and a sample solution, carrying out headspace sampling, carrying out gas chromatography analysis to obtain peak areas of all solvents, and calculating according to an external standard method by the peak areas to obtain the chromatographic column temperature change flow in gas phase detection, wherein the chromatographic column temperature change flow is as follows: the initial temperature of the chromatographic column is 35-45 ℃, the retention time is 8-12min, then the temperature is increased to 80 ℃ at the heating rate of 8-12 ℃/min, and the final temperature of the chromatographic column is 250 ℃ at the heating rate of 35-45 ℃/min, and the retention time of the final temperature of the chromatographic column is 2-5min.
2. The method for detecting residual solvent in α -ribose mesylate by gas chromatography according to claim 1, wherein the diluent is dimethyl sulfoxide solution.
3. The method for detecting residual solvent in α -ribosylate by gas chromatography according to claim 1, wherein: the carrier gas in the gas chromatography detection is nitrogen, the flow rate of the carrier gas is 2.5-3.5ml/min, and the split ratio is 20:1.
4. The method for detecting residual solvent in α -ribosylate by gas chromatography according to claim 1, wherein: the temperature of the sample inlet in the gas chromatography detection is 190-210 ℃, and the temperature of the detector is 240-260 ℃.
5. The method for detecting residual solvent in α -ribosylate by gas chromatography according to claim 1, wherein: the sample injection mode in the gas chromatography detection is headspace sample injection, the equilibrium temperature is 90 ℃, the quantitative loop temperature is 100 ℃, the transmission line temperature is 110 ℃, the equilibrium time is 30min, and the sample injection volume is 1.0mL.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106008340A (en) * | 2015-03-24 | 2016-10-12 | 上海璎黎药业有限公司 | Condensed ring derivative, preparation method, intermediate, pharmaceutical composition and application thereof |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106008340A (en) * | 2015-03-24 | 2016-10-12 | 上海璎黎药业有限公司 | Condensed ring derivative, preparation method, intermediate, pharmaceutical composition and application thereof |
Non-Patent Citations (5)
| Title |
|---|
| CHANDRAKANT SOJITRA 等: "Development and validation of residual solvent determination by headspace gas chromatography in Imatinib Mesylate API", SN APPLIED SCIENCES, vol. 01, no. 03, 14 February 2019 (2019-02-14), pages 1 - 9 * |
| 彭洁 等: "顶空气相色谱法测定卡维地洛中有机溶剂残留", 广东药学院学报, vol. 23, no. 05, 31 October 2007 (2007-10-31), pages 536 - 538 * |
| 杜薇 等: "静态顶空气相色谱法测定盐酸西那卡塞中的残留溶剂", 华西药学杂志, vol. 28, no. 03, 30 June 2013 (2013-06-30), pages 290 - 292 * |
| 由亚宁 等: "顶空气相色谱法测定丹参素冰片酯脂肪乳中溶剂残留量", 西北药学杂志, vol. 28, no. 04, 31 July 2013 (2013-07-31), pages 357 - 359 * |
| 范志先 等: "27种有机溶剂的气相色谱同时分析", 青岛科技大学学报(自然科学版), vol. 29, no. 06, 15 December 2008 (2008-12-15), pages 497 - 499 * |
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