CN113698307A - Isotope compound and preparation method and application thereof - Google Patents
Isotope compound and preparation method and application thereof Download PDFInfo
- Publication number
- CN113698307A CN113698307A CN202111048945.7A CN202111048945A CN113698307A CN 113698307 A CN113698307 A CN 113698307A CN 202111048945 A CN202111048945 A CN 202111048945A CN 113698307 A CN113698307 A CN 113698307A
- Authority
- CN
- China
- Prior art keywords
- sample
- detection
- internal standard
- detected
- standard
- 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
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C225/00—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones
- C07C225/20—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of the carbon skeleton
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/62—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating the ionisation of gases, e.g. aerosols; by investigating electric discharges, e.g. emission of cathode
-
- 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
- G01N30/04—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
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/34—Control of physical parameters of the fluid carrier of fluid composition, e.g. gradient
-
- 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
- G01N30/62—Detectors specially adapted therefor
- G01N30/72—Mass spectrometers
- G01N30/7233—Mass spectrometers interfaced to liquid or supercritical fluid chromatograph
- G01N30/724—Nebulising, aerosol formation or ionisation
- G01N30/7266—Nebulising, aerosol formation or ionisation by electric field, e.g. electrospray
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Abstract
The isotope compound provided by the invention can be used for internal standard for measuring the content of the flunomide in detection materials such as sewage, hair and the like, and qualitative detection is carried out on the flunomide according to retention time and ion pair matching. The corresponding compound is quantitatively detected according to the chromatographic peak area, and the isotope compound is used as an internal standard substance to reduce the matrix effect of a detection material, so that the isotope compound has a good application prospect in aspects such as judicial identification and the like.
Description
Technical Field
The invention belongs to the technical field of preparation and application of psychoactive substances and narcotic standard substances, and particularly relates to an isotope psychoactive substance and narcotic labeled compound, and a preparation method and application thereof.
Background
Aiming at the detection of trace and trace substances in a detected material, an isotope dilution mass spectrometry method of a liquid chromatogram-mass spectrometer combined with an isotope labeling standard substance internal standard is the most common and efficient detection means. The isotope labeled standard substance is used as an internal standard, and the isotope labeled internal standard and a compound to be detected have completely consistent chemical properties except molecular weight, so that the isotope dilution mass spectrometry can achieve high detection precision and sensitivity, and is an indispensable tool for detecting psychoactive substances and narcotics in sewage.
The detection of psychoactive substances, narcotics and related metabolites in sewage can comprehensively and visually evaluate the situation of toxic condition inundation in a city, is one of important means for urban overall toxic condition evaluation and criminal investigation by combining with the contrast of related data of drug-arresting and drug-prohibiting works, and plays a key role in urban toxic condition evaluation and key striking. The content detection of the psychoactive substances, the narcotics and the related metabolites in the hair can reflect the condition that the detected object is contacted with the psychoactive substances and the narcotics for a long time, and is an essential detection means for drug addiction judgment, community drug rehabilitation and the like.
Fluorominoketone is one of psychoactive substances and narcotics. At present, the detection method of trace amount of flunomide in environmental or biological detection materials is generally a liquid phase mass spectrometry, and the content of the flunomide in the detection materials is determined by a standard curve method by selecting a compound with similar chemical properties with the flunomide as an internal standard. The selected internal standard is generally common methoxamine, D4-ketamine or D5-diazepam and has obvious matrix effect in sewage and biological detection materials, so that the internal standard is not suitable for detection under low concentration, and the detection sensitivity is generally only 10-5% of the total weight of the composition. The effect refers to interference of substances other than the target substance in the sample material with the detection of the target substance.
Therefore, how to improve the detection accuracy and sensitivity of the content of the fluoroamine ketone in the test material is one of the technical problems to be solved urgently in the field.
Disclosure of Invention
Aiming at the problems of low detection precision and low sensitivity of the flunomide in the prior art, the invention provides an isotope labeled compound, which has the following structural formula:
wherein R is1、R2、R3、R4Is H or D, and at least one is D.
Preferably, the isotopic compound has the structural formula:
in another aspect, the present invention provides a method for preparing the isotopic compound, comprising the steps of:
(1) adding N-benzyl norflurazone and deuterated iodomethane into a reaction vessel for reaction;
for example, the reaction process is:
(2) the reaction product obtained in the step (1) is subjected to reduction reaction under the deuterium gas condition to obtain the isotope compound;
for example, the reaction process is:
the invention further provides the application of the isotope compound in detecting the content of the flunomide in biological test materials or sewage.
In the above use, the detection comprises the steps of:
(1) setting the detection conditions of liquid chromatography-mass spectrometry;
(2) drawing a standard curve: adding fludrolone and internal standard substance standard solutions in different proportions into a negative detection material corresponding to a sample to be detected to obtain a mixed standard solution, performing LC-MS/MS detection after the same pretreatment step as the sample to be detected, and making a standard curve for the peak area ratio and the concentration of the fludrolone and the internal standard substance; wherein the internal standard substance is the isotopic compound;
(3) pretreatment and determination of a sample to be detected: and adding the internal standard substance into the sample to be detected as an internal standard, performing LC-MS/MS detection after the same pretreatment step as that used in drawing the standard curve to obtain quantitative parameters of the sample to be detected and the internal standard substance, and calculating by using a formula of the standard curve of an internal standard method to obtain the content of the sample to be detected.
In the step (1), the mobile phase detected by LC-MS/MS is as follows: a: acetonitrile containing 0.01% formic acid, B: aqueous solution containing 0.01% formic acid, 5% ammonium formate, gradient: 1min 80% A, 4min 95% A, 10min 95% A; a chromatographic column: poroshell120 PFP 3.0x100mm 1.9.9 μm; column temperature: 50 ℃; flow rate: 0.5 mL/min; sample introduction amount: 5 mu L of the solution; an ion source: electrospray ion source, positive mode ESI +; the spraying voltage is 3500V; ion source temperature: 340 ℃; collision gas: nitrogen gas.
In the step (2), the mass concentration of the internal standard substance in the mixed standard solution is 0.1-99.9%.
In the step (3), the mass concentration of the internal standard substance in the sample to be detected is 0.1-99.9%.
In the step (3), the formula of the standard curve of the internal standard method is calculated as,
wherein X is the concentration of a sample to be detected, Y is the peak area obtained by LC-MS/MS detection, b0Is the intercept of the standard curve, b1Is the slope of the standard curve.
The content of the fluoroamidone in the biological detection material or the sewage is 10-9Percent to 10 percent. Preferably, a concentration of 10 can be detected-5% of fluoroamidone content, e.g. 10-7％-10-5% and less than 10-5％。
The structural formula of the isotopic compound of the present invention is exemplified as follows:
the isotope labeled compound provided by the invention can be used for internal standard of mental active substances and narcotic flumazedone content determination in sewage and biological detection materials, can reduce the matrix effect of the detection materials, and has good application prospect in aspects such as judicial identification and the like.
The invention is further described below in conjunction with the appended drawings and the detailed description.
Drawings
FIG. 1 is a high resolution mass spectrum of D7-fluoroamidone from example 1.
FIG. 2 is a drawing showing the preparation of D7-fluoroamidone in example 11H-NMR spectrum.
FIG. 3 is a drawing showing the preparation of D7-fluoroamidone in example 113C-NMR spectrum.
FIG. 4 is an extracted ion chromatogram of D7-fluoroamidone in example 1; wherein, FIG. 4(a) is a single ion chromatogram of ion pair 229.0-167.0, and FIG. 4(b) is a single ion chromatogram of ion pair 229.0-195.0.
FIG. 5 is a chromatogram for detection of a sample of the fluorocarbon amine of example 2; fig. 5(a) is a quantitative ion chromatogram of the target in example 2, fig. 5(b) is a qualitative ion verification graph of the target in example 2, and fig. 5(c) is a three-ion mass chromatogram of the target in example 2.
FIG. 6 is a standard curve of the hair fluorenone of example 2.
FIG. 7 is a chromatogram for detecting a sample of fluazinam from wastewater obtained in example 3; fig. 7(a) is a quantitative ion chromatogram of the target in example 3, fig. 7(b) is a qualitative ion verification graph of the target in example 3, and fig. 7(c) is a three-ion mass chromatogram of the target in example 3.
FIG. 8 is a standard curve of the sewage flumazelon of example 3.
Detailed Description
In order to make the technical means, the creation characteristics, the achievement purposes and the effects of the invention easy to understand, the invention is further explained below by combining the specific drawings.
In the description of the present invention, the "biological sample" refers to a human tissue sample. Such as hair, blood, urine, etc.
In the present description, the term "matrix effect" refers to the influence and interference of substances other than the analyte flunomide on the analysis process and the detection result
The invention is further illustrated by the following specific examples.
Example 1
Preparation method of D7-flunomide
D4-N-benzylnorfluridone (140mg, 0.5mmol) and cesium carbonate (1mmol) were dissolved in DMF (10mL), deuterated iodomethane (0.6mmol) was added dropwise, heated to 50 ℃ and heated for 2 hours. After cooling, the solvent was removed by rotary evaporation, dissolved by adding 5mL of dichloromethane, and then 5% mmol of Pd/C (10%) was added, and the mixture was heated to reflux for 5 hours by reduction under 1atm of deuterium gas, and then cooled to 0 ℃ and water was added dropwise. The insoluble matter was removed by Celite filtration, and the Celite was washed with 10mL of methylene chloride, and the organic phases were combined, washed with a 5% aqueous solution of sodium hydroxide and dried over anhydrous magnesium sulfate. The drying agent was removed by filtration and the solvent removed by rotary evaporation. Purification by silica gel column chromatography (petroleum ether: ethyl acetate 1: 1) gave D7-fluoroamidone as a colorless liquid (50mg, 45%).
1H NMR(600MHz,Methanol-d4)δ3.30(td,J＝4.1,3.4,2.3Hz,1H),2.57–2.47(m,2H),2.12(dtd,J＝11.8,4.0,3.5,1.8Hz,1H),1.93(ddt,J＝13.5,9.5,3.6Hz,2H),1.83–1.65(m,2H).13C NMR(151MHz,Methanol-d4)δ205.25,162.03,160.38,133.25,130.11,117.64,117.57,69.33,38.42,38.40,34.23,28.47,21.33.HR-MS(ESI/TOF)m/z:Calcd.for C13H10D7FNO[M+H]+229.1734, respectively; 229.1724 is Found. The spectrogram is shown in figures 1-3.
Example 2
And D7-flunomide is used as an internal standard to detect the content of the flunomide in the hair.
(1) Liquid chromatography-mass spectrometry detection conditions:
a) the instrument model is as follows: agilent 1290 and 6470 QQQ;
b) a chromatographic column: poroshell120 PFP 3.0x100mm 1.9.9 um;
c) column temperature: 50 ℃;
d) mobile phase: a: acetonitrile (0.01% formic acid), B: water (0.01% formic acid, 5% ammonium formate), gradient: 1min 80% A, 4min 95% A, 10min 95% A;
e) flow rate: 0.5 mL/min;
f) sample introduction amount: 5 mu L of the solution;
g) an ion source: electrospray ion source, positive mode (ESI +);
h) the spraying voltage is 3500V;
i) ion source temperature: 340 ℃;
j) collision gas: nitrogen gas.
The ion pairs and corresponding conditions are shown in table 1:
TABLE 1
(2) Pretreatment and detection of samples
Cleaning a hair sample by ultrapure water, detergent water and acetone, airing, cutting into pieces, weighing 20.0mg, adding 1mL of methanol (containing 1ng/mL of D7-fluoroaminoketone), grinding, performing ultrasonic treatment in a frozen ultrasonic instrument for 30min, centrifuging for 5min at 4000r, taking 800 mu L of supernatant, filtering by a 0.22 mu L filter membrane, and performing LC-MS/MS analysis on 5 mu L of supernatant to obtain a map shown in the attached figure 4-5. Wherein the quantitative ion pair is 191.0/222.0, and the peak area ratio of the flunomide to the internal standard D7-flunomide is 11572533/14957351.
(3) Drawing of standard curve
Cleaning blank negative hair samples with ultrapure water, detergent water and acetone, air-drying, cutting into pieces, weighing 20.0mg of each part, adding 1mL of methanol (containing 1ng/mL of D7-fluoroamidone), adding a fluoroamidone standard reference substance to prepare hair addition samples with the concentrations of 0.005, 0.01, 0.05, 0.1, 0.2, 0.5, 1.0, 2.0 and 10.0ng/mg, preparing 3 parts of each hair addition sample in parallel, vortex for 3min, standing and soaking for 30min at room temperature, treating according to a sample pretreatment process, performing LC-MS/MS detection, and making a standard curve on the peak area ratio and the concentration of the fluoroamidone and D7-fluoroamidone to obtain a graph shown in figure 6.
The formula of the standard curve is 1.401593X-0.058102, wherein X is the concentration of the sample to be detected, Y is the peak area obtained by liquid chromatogram-mass spectrum detection, b0-0.058102 is the intercept of the standard curve, b11.401593 is the slope of the standard curve.
According to the quantitative relation between the peak area ratio and the concentration in the standard curve and a calculation formula:
and calculating the content of the fludrolone in the sample to be detected to be 0.59 ng/mg.
Example 3
And D7-flunomide is used as an internal standard to detect the content of the flunomide in the sewage.
(1) Liquid chromatography-mass spectrometry detection conditions
Same as in example 1.
(2) Pretreatment and detection of samples
Filtering the sewage sample by filter paper, taking 100mL, adding 2mL of methanol (containing 10ng/mL D7-fluoroaminoketone), enabling 50mL of each sample to pass through an SPE column at the speed of 5mL/min, eluting with 5mL of methanol after the sample loading is finished, finally eluting with 5mL of 5% ammonia-acetonitrile solution, volatilizing the eluent under water bath air flow at 60 ℃, redissolving with 80 mu L of methanol, passing through a 0.22 mu L filter membrane, and performing LC-MS/MS analysis on 15 mu L of the eluent to obtain the spectra shown in the attached figures 7 and 8. Wherein the quantitative ion pair is 191.0/222.0, and the peak area ratio of the flunomide to the internal standard D7-flunomide is 857682/4864812.
(3) Drawing of standard curve
Adding 1mL of methanol (containing 100ng/mL of D7-fluoroamidone) into 50mL of a negative sewage sample, adding a fluoroamidone standard reference substance, preparing 2 parts of sewage adding samples with the concentrations of 0.5, 1, 2, 5, 20, 100 and 200ng/L in parallel, treating the samples according to a sample pretreatment process, performing LC-MS/MS detection, and making a standard curve on the peak area ratio and the concentration of the fluoroamidone and the D7-fluoroamidone to obtain a graph shown in figure 8.
The formula of the standard curve is 0.015140X +0.145096, wherein X is the concentration of the sample to be detected, Y is the peak area obtained by liquid chromatogram-mass spectrum detection, b00.145096 is the intercept of the standard curve, b10.015140 is the slope of the standard curve. According to the quantitative relation between the peak area ratio and the concentration in the standard curve and a calculation formula:
and calculating the content of the fludrolone in the sample to be detected to be 2 ng/L.
When the content of the psychoactive substance and the narcotic flumazelon in the detection material is detected, an appropriate amount of the isotope compound, such as D7-flumazelon, is added into the detection material, appropriate pretreatment is carried out according to the detection requirement, then liquid chromatography-mass spectrometry (LC-MS/MS) detection is carried out, the isotope compound is used as an internal standard, and qualitative and quantitative detection of the substance to be detected is realized by comparing the ratio of peak areas of a target substance and the substance to be detected in a Multiple Reaction Monitoring (MRM) mode, and the flumazelon detection has strong specificity and high sensitivity.
The foregoing shows and describes the general principles, essential features, and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the specification for illustrating the principles of the present invention, but that various changes and modifications may be made without departing from the spirit and scope of the invention, and these changes and modifications are within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (10)
1. An isotopic compound, wherein the isotopic compound has the formula:
wherein R is1、R2、R3、R4Is H or D, and at least one is D.
2. An isotopic compound of claim 1, wherein the formula is:
3. a method for the preparation of an isotopic compound of claim 1 or 2, comprising the steps of:
(1) adding N-benzyl norflurazone and deuterated iodomethane into a reaction vessel for reaction;
(2) the reduction reaction of the reaction product obtained in step (1) under deuterium gas condition to obtain the isotopic compound of claim 1 or 2.
4. Use of the isotopic compound of claim 1 or 2 for detecting the content of fluoroamidone in a biological sample or in waste water.
5. Use according to claim 4, characterized in that said detection comprises the following steps:
(1) setting the detection conditions of liquid chromatography-mass spectrometry;
(2) drawing a standard curve: adding fludrolone and internal standard substance standard solutions in different proportions into a negative detection material corresponding to a sample to be detected to obtain a mixed standard solution, performing LC-MS/MS detection after the same pretreatment step as the sample to be detected, and making a standard curve for the peak area ratio and the concentration of the fludrolone and the internal standard substance; wherein the internal standard is an isotopic compound of claim 1 or 2;
(3) pretreatment and determination of a sample to be detected: and adding the internal standard substance into the sample to be detected as an internal standard, performing LC-MS/MS detection after the same pretreatment step as that used in drawing the standard curve to obtain quantitative parameters of the sample to be detected and the internal standard substance, and calculating by using a formula of the standard curve of an internal standard method to obtain the content of the sample to be detected.
6. The use according to claim 4, wherein in step (1), the mobile phase of LC-MS/MS detection is: a: acetonitrile containing 0.01% formic acid, B: aqueous solution containing 0.01% formic acid, 5% ammonium formate, gradient: 1min 80% A, 4min 95% A, 10min 95% A; a chromatographic column: poroshell120 PFP 3.0x100mm 1.9.9 μm; column temperature: 50 ℃; flow rate: 0.5 mL/min; sample introduction amount: 5 mu L of the solution; an ion source: electrospray ion source, positive mode ESI +; the spraying voltage is 3500V; ion source temperature: 340 ℃; collision gas: nitrogen gas.
7. The use according to claim 5, wherein in the step (2), the mass concentration of the internal standard substance in the mixed standard solution is 0.1-99.9%.
8. The use according to claim 5, wherein in the step (3), the mass concentration of the internal standard substance in the sample to be tested is 0.1-99.9%.
9. The use according to claim 5, wherein in step (3), the formula of the internal standard method standard curve is calculated as,
wherein X is the concentration of a sample to be detected, Y is the peak area obtained by LC-MS/MS detection, b0Is the intercept of the standard curve, b1Is the slope of the standard curve.
10. The use according to claim 4, wherein the content of the fluoroamidone in the biological sample or the wastewater is 10-7％-10％。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111048945.7A CN113698307A (en) | 2021-09-08 | 2021-09-08 | Isotope compound and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111048945.7A CN113698307A (en) | 2021-09-08 | 2021-09-08 | Isotope compound and preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113698307A true CN113698307A (en) | 2021-11-26 |
Family
ID=78659170
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111048945.7A Pending CN113698307A (en) | 2021-09-08 | 2021-09-08 | Isotope compound and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113698307A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115477591A (en) * | 2022-10-26 | 2022-12-16 | 公安部第三研究所 | Isotope drug labeled compound and preparation method and application thereof |
| CN115677444A (en) * | 2022-10-26 | 2023-02-03 | 公安部第三研究所 | Isotope drug metabolite marker compound, preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112174851A (en) * | 2020-11-09 | 2021-01-05 | 广州万孚生物技术股份有限公司 | Fluoroaminoketone hapten, fludrominoketone antigen and preparation method and application thereof |
| CN112608270A (en) * | 2020-12-16 | 2021-04-06 | 李道飞 | Isotope compound and preparation method and application thereof |
| CN113321611A (en) * | 2021-02-01 | 2021-08-31 | 无锡诺平医药科技有限公司 | Isotope mental active substance labeled compound and preparation method and application thereof |
-
2021
- 2021-09-08 CN CN202111048945.7A patent/CN113698307A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112174851A (en) * | 2020-11-09 | 2021-01-05 | 广州万孚生物技术股份有限公司 | Fluoroaminoketone hapten, fludrominoketone antigen and preparation method and application thereof |
| CN112608270A (en) * | 2020-12-16 | 2021-04-06 | 李道飞 | Isotope compound and preparation method and application thereof |
| CN113321611A (en) * | 2021-02-01 | 2021-08-31 | 无锡诺平医药科技有限公司 | Isotope mental active substance labeled compound and preparation method and application thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115477591A (en) * | 2022-10-26 | 2022-12-16 | 公安部第三研究所 | Isotope drug labeled compound and preparation method and application thereof |
| CN115677444A (en) * | 2022-10-26 | 2023-02-03 | 公安部第三研究所 | Isotope drug metabolite marker compound, preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN113717066A (en) | Isotope compound and preparation method and application thereof | |
| CN113698307A (en) | Isotope compound and preparation method and application thereof | |
| CN113321611A (en) | Isotope mental active substance labeled compound and preparation method and application thereof | |
| CN111825629B (en) | Benzoxazole fluorescent probe, preparation method and application | |
| CN104761549A (en) | Palladium ion probe and preparation and application thereof | |
| CN112608270B (en) | Isotope compound and preparation method and application thereof | |
| CN108484414B (en) | Tetraphenylethylene-based formaldehyde fluorescent probe, formaldehyde detection sheet, preparation method of formaldehyde fluorescent probe and formaldehyde detection sheet, and application method of formaldehyde detection sheet | |
| CN102980968A (en) | Liquid chromatogram tandem mass spectrum measuring method for creatinine in urine | |
| CN103389351B (en) | Method for simultaneously detecting 9 acetylene-terminated hormones by virtue of liquid phase-tandem mass spectrometry | |
| CN115784995A (en) | Isotopic psychoactive substance labeled compound, preparation method and application thereof | |
| Shima et al. | Direct determination of glucuronide and sulfate of 4-hydroxy-3-methoxymethamphetamine, the main metabolite of MDMA, in human urine | |
| CN109053626B (en) | Fluorescent probe, preparation method thereof and application thereof in divalent palladium detection | |
| CN115047093B (en) | Method for detecting dimethyl sulfate in anhydrous caffeine | |
| CN110423609A (en) | A kind of fluorescence probe identifying thiocyanate radical and its preparation and recognition methods | |
| CN110563609B (en) | Preparation method and application of near-infrared fluorescent probe for detecting selenious acid roots | |
| Zhao-Fu et al. | Flow injection-chemiluminescence method for determination of hydrocortisone in human serum by using trivalent silver complex | |
| KR20090027896A (en) | Method for analysis of polyamines in urine or plasma using liquid chromatography/electronspray ionization-tandem mass spectrometry along with amine carbamylated derivatization | |
| CN115677444A (en) | Isotope drug metabolite marker compound, preparation method and application thereof | |
| CN115477591A (en) | Isotope drug labeled compound and preparation method and application thereof | |
| CN113325088A (en) | Isotope mental active substance labeled compound and preparation method and application thereof | |
| CN114478389A (en) | Isotopic psychoactive substance labeled compound, preparation method, application and application thereof | |
| CN113325089A (en) | Isotope mental active substance labeled compound and preparation method and application thereof | |
| CN112159377A (en) | Near-infrared emission simultaneous recognition H2S、HSO3-Fluorescent probe and application thereof | |
| CN113321701A (en) | Isotope mental active substance labeled compound and preparation method and application thereof | |
| Song et al. | Capillary high performance liquid chromatography coupled with electrospray ionization mass spectrometry for rapid analysis of pinane monoterpene glycosides in Cortex Moutan |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |