CN104515815A - Analysis and detection method of L-diethyl glutamate - Google Patents
Analysis and detection method of L-diethyl glutamate Download PDFInfo
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- CN104515815A CN104515815A CN201310464383.3A CN201310464383A CN104515815A CN 104515815 A CN104515815 A CN 104515815A CN 201310464383 A CN201310464383 A CN 201310464383A CN 104515815 A CN104515815 A CN 104515815A
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- mobile phase
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- pidolidone diethylester
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Abstract
The invention relates to an analysis and detection method of L-diethyl glutamate and is used in quality control of the L-diethyl glutamate. Analysis and detection are carried out through HPLC, of which chromatographic conditions are described as follows: a chromatographic column (C18, 4.6*150mm, 5[mu]m) is filled with octadecylsilane chemically bonded silica as a filling material; a mobile phase is a solution system prepared by mixing a buffer salt solution and acetonitrile and regulating a pH value to 7.0 with NaOH; a detection wavelength is 210 nm; and a column temperature is 22-32 DEG C. By means of the analysis and detection method, the L-diethyl glutamate can be effectively separated out from impurities thereof. The method is high in separation degree, is simple in operations, is good in repeatability and durability, and is stable and reliable in results.
Description
Technical field
The present invention relates to a kind of HPLC analytical method, especially the analyzing detecting method of Pidolidone diethylester.
Background technology
Pemetrexed disodium is developed by Eli Lilly company of the U.S., it is a kind of novel many target position folic acid retarding agent, multiple enzyme required in cancer cell division and hyperplastic process can be blocked, even T suppression cell thymidine and purine nucleotides biosynthesizing comprise the activity of all folate-dependant enzymes, are used for the treatment of malignant pleural mesothelioma and lung cancer in non-cellule type.
Pidolidone diethylester is the important intermediate of synthesis pemetrexed disodium, and its chemical formula is C
9h
17nO
4, structural formula is as follows:
Up to the present, the analyzing detecting method of Pidolidone diethylester is not yet recorded in document, but the analysis of Pidolidone diethylester detects has important effect to reaction controlling and yield raising, also directly affect the quality of finished product simultaneously, stablize effective analyzing detecting method so set up one quality control is carried out to Pidolidone diethylester be very important.
Summary of the invention
The object of the present invention is to provide a kind of efficient liquid phase chromatographic analysis detection method of Pidolidone diethylester, for the quality control of Pidolidone diethylester.
In order to realize object of the present invention, inventor, by lot of experiments, finally obtains following technical scheme:
The analyzing detecting method of Pidolidone diethylester, take octadecylsilane chemically bonded silica as the chromatographic column (C18 of filler, 4.6 × 150mm, 5 μm), to use the solution system of NaOH adjust pH to 7.0 for mobile phase after buffer salt solution and acetonitrile mixing, take determined wavelength as 210nm, column temperature is 22 ~ 32 DEG C, carries out high-efficient liquid phase chromatogram technique analysis detection.
Buffer salt solution in described mobile phase: the volume ratio of acetonitrile is 75 ~ 90:25 ~ 10, buffer salt solution by the sodium dihydrogen phosphate of 0.05mol/L and 0.05mol/L disodium phosphate soln by volume 94:6 form.
Further, buffer salt solution in mobile phase: the volume ratio of acetonitrile is preferably 85:15.
Described column temperature is preferably 27 DEG C.
Analyzing detecting method of the present invention, realizes by following steps:
A, to get Pidolidone diethylester sample appropriate, dissolves, be mixed with the sample solution of every 1mL containing Pidolidone diethylester 15 ~ 25mg with mobile phase;
B, to arrange flow rate of mobile phase be 0.7 ~ 1.2mL/min, determined wavelength 210nm, and column temperature is 22 ~ 32 DEG C;
C, get the sample solution 20 μ L injection liquid chromatography of A, the analysis completing Pidolidone diethylester detects;
Wherein:
High performance liquid chromatograph: Agilent1200 liquid chromatographic system;
Chromatographic column: moon rising sun XB-C18(4.6 × 150mm, 5 μm);
The disodium phosphate soln of the sodium dihydrogen phosphate of mobile phase: 0.05mol/L: 0.05mol/L: acetonitrile by volume 80:5:15 forms mobile phase (pH value is 7.0);
Determined wavelength: 210nm;
Column temperature: 27 DEG C;
Flow velocity: 1.0mL/min.
The analyzing detecting method that the present invention relates to, effectively Pidolidone diethylester and impurity thereof can be separated, and the method degree of separation is high, simple to operate, repeatability and durability good, result is reliable and stable, thus can be used for the quality control of Pidolidone diethylester, for the quality of final finished provides effective guarantee.
Accompanying drawing explanation
The Pidolidone diethylester HPLC collection of illustrative plates of Fig. 1 embodiment 1.
The Pidolidone diethylester HPLC collection of illustrative plates of Fig. 2 embodiment 2.
The Pidolidone diethylester HPLC collection of illustrative plates of Fig. 3 embodiment 3.
Embodiment
Be below specific embodiments of the invention, technical scheme of the present invention is done to describing further, but protection scope of the present invention be not limited to these embodiments.Every do not deviate from the present invention's design change or equivalent substituting include within protection scope of the present invention.
Embodiment 1
Instrument and condition: Agilent1200 liquid chromatographic system, VWD detecting device, chromatographic column: moon rising sun XB-C18(4.6 × 150mm, 5 μm), determined wavelength 210nm, column temperature 27 DEG C, the disodium phosphate soln of the sodium dihydrogen phosphate of flow velocity 1.0mL/min, 0.05mol/L: 0.05mol/L: acetonitrile by volume 80:5:15 forms mobile phase (pH value is 7.0).
Experimental procedure: Pidolidone diethylester mobile phase is dissolved and quantitatively dilutes the solution made containing Pidolidone diethylester 20mg in every 1mL, as need testing solution, precision measures need testing solution 20 μ L injection liquid chromatography, efficient liquid phase chromatographic analysis is carried out by above-mentioned condition, record chromatogram, the results are shown in accompanying drawing 1.
Accompanying drawing 1 shows, under this chromatographic condition, Pidolidone diethylester peak can be separated completely with impurity peaks, and the retention time at Pidolidone diethylester peak is at about 10.957min.
Embodiment 2
Instrument and condition: Agilent1200 liquid chromatographic system, VWD detecting device, chromatographic column: moon rising sun XB-C18(4.6 × 150mm, 5 μm), determined wavelength 210nm, column temperature 27 DEG C, the disodium phosphate soln of the sodium dihydrogen phosphate of flow velocity 0.7mL/min, 0.05mol/L: 0.05mol/L: acetonitrile by volume 70.5:4.5:25 forms mobile phase (pH value is 7.0).
Experimental procedure: Pidolidone diethylester mobile phase is dissolved and quantitatively dilutes the solution made containing Pidolidone diethylester 20mg in every 1mL, as need testing solution, precision measures need testing solution 20 μ L injection liquid chromatography, efficient liquid phase chromatographic analysis is carried out by above-mentioned condition, record chromatogram, the results are shown in accompanying drawing 2.
Accompanying drawing 2 shows, under this chromatographic condition, Pidolidone diethylester peak can be separated completely with impurity peaks, and the retention time at Pidolidone diethylester peak is at about 12.250min.
Embodiment 3
Instrument and condition: Agilent1200 liquid chromatographic system, VWD detecting device, chromatographic column: moon rising sun XB-C18(4.6 × 150mm, 5 μm), determined wavelength 210nm, column temperature 27 DEG C, the disodium phosphate soln of the sodium dihydrogen phosphate of flow velocity 1.2mL/min, 0.05mol/L: 0.05mol/L: acetonitrile by volume 84.6:5.4:10 forms mobile phase (pH value is 7.0).
Experimental procedure: Pidolidone diethylester mobile phase is dissolved and quantitatively dilutes the solution made containing Pidolidone diethylester 20mg in every 1mL, as need testing solution, precision measures need testing solution 20 μ L injection liquid chromatography, efficient liquid phase chromatographic analysis is carried out by above-mentioned condition, record chromatogram, the results are shown in accompanying drawing 3.
Accompanying drawing 3 shows, under this chromatographic condition, Pidolidone diethylester peak can be separated completely with impurity peaks, and the retention time at Pidolidone diethylester peak is at about 9.966min.
Embodiment 4
System flexibility is tested
Instrument and condition: Agilent1200 liquid chromatographic system, VWD detecting device, chromatographic column: moon rising sun XB-C18(4.6 × 150mm, 5 μm), determined wavelength 210nm, column temperature 27 DEG C, the disodium phosphate soln of the sodium dihydrogen phosphate of flow velocity 1.0mL/min, 0.05mol/L: 0.05mol/L: acetonitrile by volume 80:5:15 forms mobile phase (pH value is 7.0).
Experimental procedure: get this product in right amount, accurately weighed, add mobile phase and dissolve and dilute the solution made containing 20mg in every 1mL, as need testing solution.Get need testing solution, continuous sample introduction six times, calculate the relative standard deviation of Pidolidone diethylester peak-to-peak area and retention time respectively, experimental result is in table 1.
Table 1L-glutamate diethyl ester system suitability experimental result
As shown in Table 1, the degree of separation at Pidolidone diethylester peak and other impurities peak is all greater than 1.5, and number of theoretical plate is higher, and the relative standard deviation of peak area is 3.60%, and the relative standard deviation of retention time is 0.53%.Visible, under this chromatographic condition, Pidolidone diethylester and impurity thereof can be separated completely, and relative standard deviation is less, and acquired results is reliable and stable.
Embodiment 5
Repeated experiment
Instrument and condition: Agilent1200 liquid chromatographic system, VWD detecting device, chromatographic column: moon rising sun XB-C18(4.6 × 150mm, 5 μm), determined wavelength 210nm, column temperature 27 DEG C, the disodium phosphate soln of the sodium dihydrogen phosphate of flow velocity 1.0mL/min, 0.05mol/L: 0.05mol/L: acetonitrile by volume 80:5:15 forms mobile phase (pH value is 7.0).
Experimental procedure: get this product in right amount, accurately weighed, add mobile phase and dissolve and dilute the solution made containing 20mg in every 1mL, as need testing solution, prepare 6 parts of need testing solutions with method.Get need testing solution, continuous sample introduction six times, calculate Pidolidone diethylester content by area normalization method, and calculate its relative standard deviation, experimental result is in table 2.
Table 2L-glutamate diethyl ester repeated experiment result
As shown in Table 2, in each need testing solution, the content of Pidolidone diethylester does not have notable difference, and relative standard deviation is 0.19%, and the repeatability of visible this analysis detection method is good.
Embodiment 6
Durability is tested
Instrument and condition: Agilent1200 liquid chromatographic system, VWD detecting device, the disodium phosphate soln of the sodium dihydrogen phosphate of determined wavelength 210nm, 0.05mol/L: 0.05mol/L: acetonitrile by volume 80:5:15 forms mobile phase (pH value is 7.0).
Experimental procedure: get this product in right amount, accurately weighed, add mobile phase and dissolve and dilute the solution made containing 20mg in every 1mL, as need testing solution.Respectively by change column temperature, flow velocity and chromatographic column type, the situation of change (calculating by area normalization method) of record Pidolidone diethylester content, experimental result is in table 3.
Table 3L-glutamate diethyl ester durability experimental result
As shown in Table 3, after changing column temperature, flow velocity and determined wavelength, the measurement result of Pidolidone diethylester content does not have notable difference, the good tolerance of visible analyzing detecting method of the present invention.
Claims (5)
- The analyzing detecting method of 1.L-glutamate diethyl ester, adopts high performance liquid chromatography to carry out analysis and detects, it is characterized in that comprising the following steps:A, to get Pidolidone diethylester sample appropriate, dissolves, be mixed with the sample solution of every 1mL containing Pidolidone diethylester 15 ~ 25mg with mobile phase;B, to arrange flow rate of mobile phase be 0.7 ~ 1.2mL/min, determined wavelength 210nm, and column temperature is 22 ~ 32 DEG C;C, get the sample solution 20 μ L injection liquid chromatography of A, the analysis completing Pidolidone diethylester detects;Wherein, chromatographic column: C18,4.6 × 150mm, 5 μm;Described mobile phase after buffer salt solution mixes with acetonitrile is the solution system of 7.0 with NaOH adjust pH, counts by volume, buffer salt solution: acetonitrile is 75 ~ 90:25 ~ 10.
- 2. analyzing detecting method as claimed in claim 1, is characterized in that: described sample solution concentration is 20mg/mL.
- 3. analyzing detecting method as claimed in claim 1, it is characterized in that: described flow rate of mobile phase is 1.0mL/min, column temperature is 27 DEG C.
- 4. analyzing detecting method as claimed in claim 1, is characterized in that: described buffer salt solution by the sodium dihydrogen phosphate of 0.05mol/L and 0.05mol/L disodium phosphate soln by volume 94:6 form.
- 5. analyzing detecting method as claimed in claim 1, is characterized in that: buffer salt solution in described mobile phase: the volume ratio of acetonitrile is 85:15.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110749692A (en) * | 2019-10-15 | 2020-02-04 | 扬子江药业集团有限公司 | Separation and detection method of L-glutamic acid diethyl ester hydrochloride and optical isomer thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101411710A (en) * | 2008-11-25 | 2009-04-22 | 江苏奥赛康药业有限公司 | Pemetrexed disodium freeze-dried injection and preparation method thereof |
| WO2011019986A2 (en) * | 2009-08-13 | 2011-02-17 | Dr. Reddy's Laboratories Ltd. | Processes for preparing pemetrexed |
| CN102911176A (en) * | 2012-10-10 | 2013-02-06 | 德州德药制药有限公司 | Preparation method of pemetrexed disodium |
-
2013
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101411710A (en) * | 2008-11-25 | 2009-04-22 | 江苏奥赛康药业有限公司 | Pemetrexed disodium freeze-dried injection and preparation method thereof |
| WO2011019986A2 (en) * | 2009-08-13 | 2011-02-17 | Dr. Reddy's Laboratories Ltd. | Processes for preparing pemetrexed |
| CN102911176A (en) * | 2012-10-10 | 2013-02-06 | 德州德药制药有限公司 | Preparation method of pemetrexed disodium |
Non-Patent Citations (3)
| Title |
|---|
| G. SARAVANAN ET AL.: "A Stability-Indicating LC Assay Method for Pemetrexed Disodium", 《CHROMATOGRAPHIA》 * |
| 张静 等: "培美曲塞二钠的合成研究进展", 《河北化工》 * |
| 林斌: "高效液相色谱法测定培美曲塞二钠有关物质的方法学研究", 《第六届海南省科技论坛"医药科技创新与药品质量安全"专题论坛、海南省药学会2012年学术年会论文集》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110749692A (en) * | 2019-10-15 | 2020-02-04 | 扬子江药业集团有限公司 | Separation and detection method of L-glutamic acid diethyl ester hydrochloride and optical isomer thereof |
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Application publication date: 20150415 |