CN114689763A - Method for determining and analyzing content of compound I in oxa-goril sodium - Google Patents
Method for determining and analyzing content of compound I in oxa-goril sodium Download PDFInfo
- Publication number
- CN114689763A CN114689763A CN202011564779.1A CN202011564779A CN114689763A CN 114689763 A CN114689763 A CN 114689763A CN 202011564779 A CN202011564779 A CN 202011564779A CN 114689763 A CN114689763 A CN 114689763A
- Authority
- CN
- China
- Prior art keywords
- solution
- compound
- sodium
- acid
- sample
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 title claims abstract description 30
- 229910052708 sodium Inorganic materials 0.000 title claims abstract description 30
- 239000011734 sodium Substances 0.000 title claims abstract description 30
- 238000000034 method Methods 0.000 title claims abstract description 18
- 150000001875 compounds Chemical class 0.000 title claims description 49
- XWSGEVNYFYKXCP-UHFFFAOYSA-N 2-[carboxymethyl(methyl)amino]acetic acid Chemical compound OC(=O)CN(C)CC(O)=O XWSGEVNYFYKXCP-UHFFFAOYSA-N 0.000 claims abstract description 11
- JCKZNMSBFBPDPM-UHFFFAOYSA-N (2-fluoro-3-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC(B(O)O)=C1F JCKZNMSBFBPDPM-UHFFFAOYSA-N 0.000 claims abstract description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 51
- 239000000523 sample Substances 0.000 claims description 35
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 32
- 239000000243 solution Substances 0.000 claims description 27
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 26
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 21
- 239000003795 chemical substances by application Substances 0.000 claims description 21
- 150000002500 ions Chemical class 0.000 claims description 21
- 239000003085 diluting agent Substances 0.000 claims description 19
- 239000011550 stock solution Substances 0.000 claims description 19
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 18
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 16
- 235000019253 formic acid Nutrition 0.000 claims description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 14
- 238000001819 mass spectrum Methods 0.000 claims description 13
- 238000001212 derivatisation Methods 0.000 claims description 11
- 239000007788 liquid Substances 0.000 claims description 11
- 238000002156 mixing Methods 0.000 claims description 11
- 238000010586 diagram Methods 0.000 claims description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 238000010438 heat treatment Methods 0.000 claims description 7
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 claims description 7
- 239000012488 sample solution Substances 0.000 claims description 7
- 239000000377 silicon dioxide Substances 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 4
- XXMFJKNOJSDQBM-UHFFFAOYSA-N 2,2,2-trifluoroacetic acid;hydrate Chemical compound [OH3+].[O-]C(=O)C(F)(F)F XXMFJKNOJSDQBM-UHFFFAOYSA-N 0.000 claims description 3
- 238000010828 elution Methods 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 239000002994 raw material Substances 0.000 claims description 2
- 238000005070 sampling Methods 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- 238000009795 derivation Methods 0.000 claims 1
- 231100000024 genotoxic Toxicity 0.000 claims 1
- 230000001738 genotoxic effect Effects 0.000 claims 1
- 239000012535 impurity Substances 0.000 claims 1
- 230000035945 sensitivity Effects 0.000 abstract description 4
- 238000004458 analytical method Methods 0.000 abstract description 2
- 238000004454 trace mineral analysis Methods 0.000 abstract description 2
- 239000012071 phase Substances 0.000 description 12
- 238000007865 diluting Methods 0.000 description 6
- 238000005303 weighing Methods 0.000 description 6
- 238000001816 cooling Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 239000012086 standard solution Substances 0.000 description 3
- 230000007547 defect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- HEAUOKZIVMZVQL-VWLOTQADSA-N Elagolix Chemical compound COC1=CC=CC(C=2C(N(C[C@H](NCCCC(O)=O)C=3C=CC=CC=3)C(=O)N(CC=3C(=CC=CC=3F)C(F)(F)F)C=2C)=O)=C1F HEAUOKZIVMZVQL-VWLOTQADSA-N 0.000 description 1
- 102000008238 LHRH Receptors Human genes 0.000 description 1
- 108010021290 LHRH Receptors Proteins 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012483 derivatization solution Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000000745 gonadal hormone Substances 0.000 description 1
- 239000002474 gonadorelin antagonist Substances 0.000 description 1
- 229940121381 gonadotrophin releasing hormone (gnrh) antagonists Drugs 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Images
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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
-
- 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
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
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)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
Abstract
The invention discloses a method for determining and analyzing the content of 2-fluoro-3-methoxyphenylboronic acid in oxa-gol sodium, which determines the content of 2-fluoro-3-methoxyphenylboronic acid derivatives in the oxa-gol sodium by deriving the derivatives with N-methyliminodiacetic acid. Compared with the prior art, the analysis method has the characteristics of good specificity, good reproducibility, extremely high sensitivity, suitability for trace analysis and the like.
Description
Technical Field
The invention relates to a method for determining the content of 2-fluoro-3-methoxyphenylboronic acid (hereinafter referred to as compound I derivative) in oxadegril sodium by using a high performance liquid chromatography-mass spectrometer to determine the content of the 2-fluoro-3-methoxyphenylboronic acid (hereinafter referred to as compound I derivative) after being derived from N-methyliminodiacetic acid (hereinafter referred to as a derivative). The method can well control the content of the trace compound I in the bulk drugs and preparations, provides guarantee for the healthy and safe medication of patients, and belongs to the technical field of medicines.
Technical Field
Sodium oxadegril having the chemical name R-4- ((2- (5- (2-fluoro-3-methoxyphenyl) -3- ((2-fluoro-6- (trifluoromethyl) benzyl) -4-methyl-2, 6-dioxo-2, 3-dihydropyrimidin-1 (6H) -yl) -1-phenylethyl) amino) butanoate.
Oxalagrol sodium (elagolix sodium) is an oral GnRH antagonist developed by aiberlite (Abbvie) and Neurocrine Biosciences, a partner, which ultimately reduces the level of gonadal hormones in the blood circulation by inhibiting pituitary gonadotropin-releasing hormone receptors. The structure is as follows:
the compound I containing reaction residues in the oxalagogrel sodium has the following structure:
accurate quantitative determination of trace amounts of compound I in oxalagril sodium is extremely challenging. It is difficult to directly measure the trace amount by gas chromatography, liquid chromatography and the like.
At present, only a method for measuring the content of a constant compound I adopts a classical chromatography, so that the specificity, the sensitivity, the method precision and the repeatability of the method have great defects, and a reliable trace analysis result cannot be provided. In order to overcome the defects of the original method, the content of the compound I in the oxagoril sodium is determined by adopting a high performance liquid chromatography-mass spectrometer and derivatization with a derivatization agent. The analysis method has the characteristics of simple operation, good specificity, extremely high sensitivity, good reproducibility and the like.
Disclosure of Invention
As mentioned above, there are various drawbacks to the direct and accurate quantitative determination of trace amounts of compound I. However, the high performance liquid chromatography-mass spectrometer can be used for determination by utilizing the characteristics that the compound I has high reaction activity with a derivative agent and mild reaction conditions, the derivative has the characteristics of strong stability and suitability for reversed phase liquid chromatography separation, and the derivative is easy to ionize in a mass spectrometer detector and has a stable molecular structure suitable for quantitative analysis. In addition, the characteristic that the compound I has sensitive response in a mass spectrum detector greatly improves the sensitivity and specificity of the method.
The derivatizing agent N-methyliminodiacetic acid has the following structure:
the reaction route of the compound I and the derivative N-methyliminodiacetic acid to generate the compound I derivative is as follows:
experiments show that the oxadegril sodium has very good solubility in the dimethyl sulfoxide, the reaction efficiency of the compound I and the derivatization agent in the acidic dimethyl sulfoxide is high, and the conditions are mild and easy to operate. The present invention will use dimethyl sulfoxide as a diluent.
The invention relates to a method for determining and analyzing the content of a compound I in oxa-gol sodium.
The above sample preparation uses 10% acetic acid in dimethylsulfoxide as a diluent.
The method adopts a high performance liquid chromatography-mass spectrometer and selects a positive ion mode.
The method comprises the following steps:
(1) taking the raw material medicine or preparation powder of the oxa-goril sodium, and taking a dimethyl sulfoxide or N, N-dimethylformamide solution of 5-30% formic acid or acetic acid or trifluoroacetic acid as a diluent to prepare a sample stock solution;
(2) preparing a derivatization agent solution by taking a derivatization agent N-methyliminodiacetic acid solid and taking dimethyl sulfoxide or N, N-dimethylformamide solution of 5-30% formic acid, acetic acid or trifluoroacetic acid as a diluent;
(3) uniformly mixing the sample stock solution and the derivative solution according to a certain volume ratio, heating the mixture in an oven to 50-150 ℃, and reacting for 20 minutes-10 hours to prepare a sample solution;
(4) octadecylsilane chemically bonded silica chromatographic column is adopted, and the mobile phase is 0.05-0.2% formic acid or acetic acid or trifluoroacetic acid water solution and acetonitrile or methanol for isocratic or gradient elution.
(5) Setting the flow rate of the mobile phase at 0.3-2.0mL/min, and controlling the column temperature at 25-45 ℃.
(6) And (3) selecting positive ions in an ion mode by adopting a mass spectrum detector, sampling the sample solution in the step (3), and recording a mass spectrum ion flow diagram of the derivative of the compound I.
The technical scheme adopted by the invention is as follows:
sample pretreatment:
diluting liquid: 5% to 30% formic acid or acetic acid or trifluoroacetic acid in dimethylsulfoxide or N, N-dimethylformamide.
Solution of derivatizing agent: 100mg of the derivatization agent N-methyliminodiacetic acid is weighed out in a 10ml volumetric flask, dissolved and diluted to the scale with the diluent, and shaken up.
Standard stock solutions of compound I: and precisely preparing 200ng/ml of compound I solution by using the diluent.
Sample stock solution: precisely weighing 400mg of sample in a 10ml volumetric flask, dissolving and diluting to the scale with diluent, and shaking up.
Standard solution of compound I: mixing 500 μ l of compound I standard stock solution and 500 μ l of derivative solution in 1.5ml sample vial, and heating at 100 deg.C for 1 hr.
Sample solution: the sample stock solution and 500. mu.l of the derivatizing agent solution were mixed in a 1.5ml sample vial and heated at 100 ℃ for 1 hour.
The chromatographic column used in the invention is as follows: octadecylsilane chemically bonded silica chromatographic column. The flow rate is 0.3-2.0 mL/min. The column temperature is 25-45 ℃. Mobile phase A: 0.05% -0.2% aqueous formic acid or acetic acid or trifluoroacetic acid, mobile phase B: acetonitrile or methanol, isocratic or gradient elution.
A mass spectrometry detector: positive ion mode, [ M ]+H]+:282
Description of the drawings:
FIG. 1: a mass spectrometric bar chart of a derivative of compound I obtained according to example 1 of the present invention;
FIG. 2 is a drawing: a mass spectrum total ion flow chart of the derivative of the compound I obtained in the embodiment 2 of the invention;
FIG. 3: the total ion flow diagram of the mass spectrum of the Oxagolide sodium sample obtained according to the embodiment 3 of the invention;
FIG. 4 is a drawing: recovering a mass spectrum total ion flow diagram from the obtained Oxagolide sodium sample according to the embodiment 4 of the invention;
Detailed Description
For better understanding of the technical solutions of the present invention, the following embodiments are further described, but not limited to, the present invention.
Example one
Instruments and conditions:
high performance liquid chromatography mass spectrometer: agilent 1260 definition, MS Detector.
A chromatographic column: octadecylsilane chemically bonded silica chromatographic column
Mobile phase: a: 0.05% -0.2% of formic acid or acetic acid or trifluoroacetic acid aqueous solution B and acetonitrile.
The isocratic degree is as follows: 0-8.0 min, 5% of organic phase.
Column temperature: at 40 ℃.
Flow rate: 0.6mL/min
Selecting positive ions: 282
Sample introduction volume: 3 ul.
The experimental steps are as follows:
1) preparing a mobile phase A: precisely measuring 1.0mL of formic acid, dissolving in 1000mL of water, and uniformly mixing.
2) Diluting liquid: 10% acetic acid in dimethyl sulfoxide
3) Solution of derivatizing agent: 100mg of the derivatization agent N-methyliminodiacetic acid is weighed out in a 10ml volumetric flask, dissolved and diluted to the scale with the diluent, and shaken up.
4) Compound I derivatization solution: precisely weighing about 20mg of the compound I in a 10ml volumetric flask, adding the diluent to dissolve and dilute the compound I to a scale, and shaking up to obtain a derivative stock solution of the compound I. Precisely transferring 0.5ml of derivative stock solution of the compound I into a sample injection vial, precisely transferring 0.5ml of derivative agent solution into the sample injection vial, fully mixing, heating in an oven at 100 ℃ for 1 hour, cooling to obtain derivative solution of the compound I, injecting, and recording a mass spectrum bar chart of the derivative of the compound I, which is shown in a typical chart 1.
Example two
Instruments and conditions:
high performance liquid chromatography mass spectrometer: agilent 1260 definition, MS Detector.
A chromatographic column: octadecylsilane chemically bonded silica chromatographic column
Mobile phase: a: 0.05% -0.2% of formic acid or acetic acid or trifluoroacetic acid aqueous solution B and acetonitrile.
The isocratic is as follows: 0-8.0 min, 5% of organic phase.
Column temperature: at 40 ℃.
Flow rate: 0.6mL/min
Selecting positive ions: 282
Sample introduction volume: 3 ul.
The experimental steps are as follows:
1) preparing a mobile phase A: precisely measuring 1.0mL of formic acid, dissolving in 1000mL of water, and uniformly mixing.
2) Diluting liquid: 10% acetic acid in dimethylsulfoxide.
3) Solution of derivatizing agent: 100mg of the derivatization agent N-methyliminodiacetic acid is weighed out in a 10ml volumetric flask, dissolved and diluted to the scale with the diluent, and shaken up.
4) Standard solution of compound I: precisely weighing about 20mg of the compound I in a 10ml volumetric flask, adding a diluent to dissolve and dilute the compound I to a scale, shaking up, precisely transferring 100 mu l of the compound I in another 10ml volumetric flask, adding the diluent to a constant volume, shaking up, precisely transferring 100 mu l of the compound I in another 10ml volumetric flask, and shaking up to obtain the standard stock solution of the compound I. Precisely transferring 0.5ml of the standard stock solution of the compound I into a 1.5ml sample vial, precisely transferring 0.5ml of the derivative solution into the sample vial, fully mixing, heating in an oven at 100 ℃ for 1 hour, cooling to obtain the standard solution of the compound I, injecting, and recording the total ion flow diagram of the derivative mass spectrum of the compound I, which is shown in a typical diagram 2.
EXAMPLE III
Instruments and conditions:
high performance liquid chromatography mass spectrometer: agilent 1260 definition, MS Detector.
A chromatographic column: octadecylsilane chemically bonded silica chromatographic column
Mobile phase: a: 0.05% -0.2% of formic acid or acetic acid or trifluoroacetic acid aqueous solution B and acetonitrile.
The isocratic degree is as follows: 0-8.0 min, 5% of organic phase.
Column temperature: at 40 ℃.
Flow rate: 0.6mL/min
Selecting positive ions: 282
Sample introduction volume: 3 ul.
The experimental steps are as follows:
1) preparing a mobile phase A: precisely measuring 1.0mL of formic acid, dissolving in 1000mL of water, and uniformly mixing.
2) Diluting liquid: 10% acetic acid in dimethylsulfoxide.
3) Solution of derivatizing agent: 100mg of the derivatization agent N-methyliminodiacetic acid is weighed out in a 10ml volumetric flask, dissolved and diluted to the scale with the diluent, and shaken up.
4) Sample solution of oxa-rogatide sodium: precisely weighing about 400 portions of oxapogril sodium into a 10ml volumetric flask, adding a diluent to dissolve and dilute the oxapogril sodium to a scale, and shaking up to obtain an oxapogril sodium sample stock solution. Precisely transferring 0.5ml of an oxagoril sodium sample stock solution into a 1.5ml sample vial, precisely transferring 0.5ml of a derivatizing agent solution into the sample vial, fully mixing, heating in an oven at 100 ℃ for 1 hour, cooling to obtain an oxagoril sodium sample solution, carrying out sample introduction, and recording a mass spectrum total ion flow diagram of the oxagoril sodium sample, wherein the mass spectrum total ion flow diagram is shown in a typical diagram 3.
Example four
Instruments and conditions:
high performance liquid chromatography mass spectrometer: agilent 1260 definition, MS Detector.
A chromatographic column: octadecylsilane chemically bonded silica chromatographic column
Mobile phase: a: 0.05% -0.2% formic acid or acetic acid or trifluoroacetic acid water solution B acetonitrile.
The isocratic degree is as follows: 0-8.0 min, 5% of organic phase.
Column temperature: at 40 ℃.
Flow rate: 0.6mL/min
Selecting positive ions: 282
Sample introduction volume: 3 ul.
The experimental steps are as follows:
1) preparing a mobile phase A: precisely measuring 1.0mL of formic acid, dissolving in 1000mL of water, and uniformly mixing.
2) Diluting liquid: 10% acetic acid in dimethylsulfoxide.
3) Solution of derivatizing agent: 100mg of derivative N-methyliminodiacetic acid is weighed into a 10ml volumetric flask, dissolved and diluted to the mark by the diluent, and shaken up.
4) Standard stock solutions of compound I: precisely weighing about 20mg of the compound I in a 10ml volumetric flask, adding a diluent to dissolve and dilute the compound I to a scale, shaking up, precisely transferring 100 mu l of the compound I in another 10ml volumetric flask, adding the diluent to a constant volume, shaking up, precisely transferring 100 mu l of the compound I in another 10ml volumetric flask, and shaking up to obtain the standard stock solution of the compound I.
5) Recovering a solution from a sample of oxagoril: precisely weighing about 400mg of oxa-rogue sodium into a 10ml volumetric flask, adding a standard stock solution of the compound I to dissolve to a constant volume, and shaking up to obtain a recycling stock solution of an oxa-rogue sodium sample. Precisely transferring 0.5ml of the recovery stock solution of the sodium oxogolate sample into a 1.5ml sample vial, precisely transferring 0.5ml of the solution of the derivatizing agent into the sample vial, fully mixing, heating in an oven at 100 ℃ for 1 hour, cooling to obtain the recovery solution of the sodium oxogolate sample, carrying out sample introduction, and recording the total ion flow diagram of the recovery mass spectrum of the sodium oxogolate sample, which is shown in a typical figure 4.
Claims (3)
1. A method for determining and analyzing the content of 2-fluoro-3-methoxyphenylboronic acid (hereinafter referred to as compound I) which is a suspected genotoxic impurity in oxagoril sodium is characterized in that the content of trace compound I in the oxagoril sodium is determined by a high performance liquid chromatography-mass spectrometer through a derivation method.
2. The method of claim 1, wherein the positive ion is selected for ion mode using a high performance liquid chromatography-mass spectrometer.
3. The method according to claim 1, characterized in that the method comprises the following steps:
(1) taking the oxagolide sodium raw material medicine or preparation powder, and taking a dimethyl sulfoxide or N, N-dimethylformamide solution of 5-30% formic acid or acetic acid or trifluoroacetic acid as a diluent to prepare a sample stock solution;
(2) preparing a derivatization agent solution by taking a derivatization agent N-methyliminodiacetic acid solid and taking dimethyl sulfoxide or N, N-dimethylformamide solution of 5-30% formic acid, acetic acid or trifluoroacetic acid as a diluent;
(3) uniformly mixing the sample stock solution and the derivative solution according to a certain volume ratio, heating the mixture in an oven to 50-150 ℃, and reacting for 20 minutes-10 hours to prepare a sample solution;
(4) octadecylsilane chemically bonded silica chromatographic column is adopted, and the mobile phase is 0.05-0.2% formic acid or acetic acid or trifluoroacetic acid water solution and acetonitrile or methanol for isocratic or gradient elution.
(5) Setting the flow rate of the mobile phase at 0.3-2.0mL/min, and controlling the column temperature at 25-45 ℃.
(6) And (4) selecting positive ions by adopting a mass spectrum detector in an ion mode, sampling the sample solution obtained in the step (3), and recording a mass spectrum ion flow diagram of the derivative of the compound I.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011564779.1A CN114689763A (en) | 2020-12-25 | 2020-12-25 | Method for determining and analyzing content of compound I in oxa-goril sodium |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011564779.1A CN114689763A (en) | 2020-12-25 | 2020-12-25 | Method for determining and analyzing content of compound I in oxa-goril sodium |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114689763A true CN114689763A (en) | 2022-07-01 |
Family
ID=82129067
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011564779.1A Pending CN114689763A (en) | 2020-12-25 | 2020-12-25 | Method for determining and analyzing content of compound I in oxa-goril sodium |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114689763A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116026966A (en) * | 2022-11-09 | 2023-04-28 | 哈药集团技术中心 | Detection method for determining related substances of oxaagole sodium by HPLC |
-
2020
- 2020-12-25 CN CN202011564779.1A patent/CN114689763A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116026966A (en) * | 2022-11-09 | 2023-04-28 | 哈药集团技术中心 | Detection method for determining related substances of oxaagole sodium by HPLC |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN113049719A (en) | Method and kit for detecting free testosterone | |
| Wang et al. | Simultaneous determination of creatine phosphate, creatine and 12 nucleotides in rat heart by LC–MS/MS | |
| CN114689763A (en) | Method for determining and analyzing content of compound I in oxa-goril sodium | |
| CN113295805B (en) | Method for detecting hydrazine hydrate in medicine | |
| CN106932502B (en) | Method for determining content of 4-chloro-2-picolinic acid methyl ester in sorafenib | |
| Thompson et al. | Carbon and nitrogen isotopic analysis of morphine from opium and heroin samples originating in the four major heroin producing regions | |
| CN109975435A (en) | The measuring method of isopropyl mesylate content in a kind of safinamide | |
| CN109307716B (en) | Detection method of brexpiprazole related substance | |
| CN106814144B (en) | Method for determining and analyzing content of dimethyl sulfate in dimethyl fumarate | |
| Yang et al. | Comparison of sector field-and quadrupole-ICP-MS for the determination of DBT and TBT in sediment following GC separation | |
| Gong et al. | Purity assessment of luteolin reference material candidates by coulometric titration method | |
| CN100480698C (en) | Method for inspecting hypotensive medicine | |
| CN114047279A (en) | Method for measuring residual quantity of N-methylpiperazine in drug intermediate and bulk drug by high performance liquid chromatography-mass spectrometry | |
| CN111366660A (en) | Method for measuring content of dimethyl sulfate in Etegravir | |
| Ganjali et al. | Terazosin potentiometric sensor for quantitative analysis of terazosin hydrochloride in pharmaceutical formulation based on computational study | |
| CN111624263A (en) | Determination and analysis method for IMP17 content in brexpiprazole | |
| CN113030352B (en) | Determination and analysis method for NMBA content in irbesartan | |
| CN116359362A (en) | Method for measuring and analyzing content of ethyl carbamate in reevaluables | |
| CN113624894B (en) | Method for detecting nitrosamine impurities in biapenem | |
| CN116465990B (en) | Detection method for impurities of 1, 5-hexanediol, 1, 6-hexanediol and 3-methyl-1, 5-pentanediol in atracurium besylate and cis atracurium besylate bulk drug | |
| CN108956809B (en) | Method for detecting 1- (1-chloroethyl) -2, 3-xylene related substances | |
| CN116359360A (en) | Determination analysis method for compound I content in HHT-109 raw material | |
| CN117269402B (en) | Liquid phase mass spectrum combination method for quantitatively detecting norcinnabar in human cerebrospinal fluid | |
| AU2021101493A4 (en) | Method for simultaneously measuring mb-x and azbc impurities in irbesartan raw materials and preparations | |
| CN114088843A (en) | Method for detecting nitrosamine genotoxic impurities in varenicline intermediate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| CB02 | Change of applicant information |
Address after: No. 538, Cailun Road, Zhangjiang High Tech Park, Pudong New Area, Shanghai, 201203 Applicant after: Shanghai Aobo biomedical Co.,Ltd. Applicant after: ZHEJIANG HUAHAI PHARMACEUTICAL Co.,Ltd. Address before: No. 538, Cailun Road, Zhangjiang High Tech Park, Pudong New Area, Shanghai, 201203 Applicant before: SHANGHAI AOBO PHARMTECH, Inc.,Ltd. Applicant before: ZHEJIANG HUAHAI PHARMACEUTICAL Co.,Ltd. |
|
| CB02 | Change of applicant information | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |