Carbon-13 labeled psychoactive substances and methods of making and using the same

Abstract

This invention relates to carbon-13 labeled psychoactive substances, the chemical structural formula of which is: . This invention also provides a method for preparing the aforementioned carbon-13 labeled psychoactive substances, comprising the following steps: (1) 13 C-C3-alanine reacts with Boc2O and a methylating agent to form N-methyl-N-Boc- 13 (2) The product obtained in step (1) is reacted with N,O-dimethylhydroxylamine to obtain an intermediate; (3) The intermediate obtained in step (2) is reacted with a phenyl nucleophile to obtain 13 C-C3-2-N-Boc-methylamino-1-phenyl-1-propanone; (4) The product obtained in step (3) is subjected to a Boc protecting group removal reaction to obtain the carbon 13-labeled psychoactive substance. The present invention also provides the use of the carbon 13-labeled psychoactive substance in detecting the content of methcathinone in biological or environmental samples.

Description

Technical Field

[0001] This invention relates to the field of preparation and application technology of psychoactive substance standard materials, specifically to a carbon-13 labeled psychoactive substance and its preparation method and uses. Background Technology

[0002] In recent years, the abuse of psychoactive substances has shown a trend of increased concealment and diversity, placing higher demands on accurate detection technologies. In particular, in the trace analysis of new drugs such as methcathinone (2-methylamino-1-phenyl-1-propanone), the matrix effect and insufficient internal standard matching have become the core bottleneck restricting the accuracy of detection.

[0003] Currently, liquid chromatography-tandem mass spectrometry (LC-MS / MS) is the mainstream detection method, relying on internal standards to correct for the extraction efficiency of the target analyte and ionization interference. However, existing internal standards mostly use chemically similar compounds (such as D5-cathinone or D5-diazepam), which differ significantly from the target analyte in molecular structure. This results in insufficient isotope dilution effect, making it difficult to completely offset interference from complex biological matrices (such as hair and blood), thus affecting the reliability of quantitative results.

[0004] Isotope dilution mass spectrometry (IDMS), with its ultra-high sensitivity and resistance to matrix interference, has become the gold standard for the detection of trace psychoactive substances. This method uses isotope-labeled compounds (such as carbon-13 or deuterated labels) as internal standards, whose physicochemical properties are highly consistent with the target analyte, differing only in molecular weight. In mass spectrometry analysis, the internal standard and the target analyte have nearly identical ionization efficiency and chromatographic behavior, enabling real-time correction of pretreatment losses and instrument fluctuations, significantly improving detection accuracy (recovery > 85%, relative standard deviation < 5%). Studies have shown that structural homology between the internal standard and the target analyte is key to reducing matrix effects. Currently, there is a lack of specific isotope internal standards for methcathinone detection, necessitating the development of structurally matched labeled compounds.

[0005] Hair samples offer irreplaceable advantages in drug control practices due to their ability to trace drug exposure history up to six months. However, the concentration of target substances in hair is extremely low (typically in the pg / mg range), and interference factors such as pigment binding and exogenous contamination pose stringent requirements for the sensitivity and specificity of analytical methods. Current technologies, due to insufficient internal standard compatibility, struggle to achieve stable quantification of methcathinone in hair matrix, thus limiting the scientific rigor and legal validity of drug control forensic identification.

[0006] Wastewater, as an environmental sample, also possesses unique advantages in drug control practice: it collects the excrement of people in a specific area, and by analyzing the residual concentration of drugs and their metabolites, it provides a scientific basis for regional drug situation assessment and monitoring of drug control effectiveness. However, wastewater samples have a complex matrix, containing a large amount of suspended solids, microorganisms, and chemical interfering substances, requiring extremely high sensitivity and specificity from analytical methods. Existing technologies, due to insufficient internal standard compatibility, struggle to achieve stable quantification of methcathinone in complex wastewater matrices, which also restricts the scientific rigor and legal validity of drug control forensic identification.

[0007] In summary, the trace detection of methcathinone in complex matrices such as hair and sewage places extremely high demands on the sensitivity, accuracy, and anti-interference capabilities of analytical methods. While isotope dilution mass spectrometry is widely recognized as the gold standard for trace analysis, its accuracy and reproducibility are not reliably guaranteed due to the lack of a structurally highly matched dedicated isotope internal standard. Therefore, developing an isotope-labeled internal standard with the same physicochemical properties as methcathinone and constructing a stable and accurate trace detection method has become a critical technical problem urgently needing to be solved in the field of drug control detection. Summary of the Invention

[0008] The purpose of this invention is to overcome the defects in the prior art. This invention provides a carbon-13 labeled psychoactive substance, its preparation method and uses, and solves the problems of low accuracy and low sensitivity in the detection of methcathinone.

[0009] To achieve the above objectives, a first aspect of the present invention provides a carbon-13 labeled psychoactive substance, characterized in that its chemical structural formula is: .

[0010] A second aspect of the present invention provides a method for preparing the carbon-13 labeled psychoactive substance, characterized in that it includes the following steps: (1) 13 C-C3-alanine is converted to N-methyl-N-Boc- by Boc2O and a methylating agent. 13 C-C3-alanine; (2) The product obtained in step (1) is reacted with N,O-dimethylhydroxylamine to obtain an intermediate; (3) The intermediate obtained in step (2) is reacted with a phenyl nucleophile to obtain 13 C-C3-2-N-Boc-methylamino-1-phenyl-1-propanone; (4) The product obtained in step (3) is subjected to a Boc protecting group removal reaction to obtain carbon 13 labeled methcathinone.

[0011] Preferably, in step (1), the methylating agent is formaldehyde.13 C-C3-alanine first reacts with Boc2O, then with formaldehyde at 20°C to 30°C for 20 to 28 hours, and finally with sodium cyanohydride at 20°C to 30°C for 44 to 52 hours. In step (2), the reaction time is 10 to 14 hours and the reaction temperature is -5°C to 5°C; In step (3), the catalyst is CuI, the solvent is THF, the phenyl nucleophile is phenyl magnesium bromide, the reaction time is 10 to 14 hours, and the reaction temperature is -5℃ to 5℃.

[0012] A third aspect of the invention provides the use of the carbon-13 labeled methcathinone or the carbon-13 labeled methcathinone prepared by the preparation method described above in detecting the content of methcathinone in biological or environmental samples.

[0013] Preferably, the carbon-13 labeled methcathinone is used as an isotopic internal standard.

[0014] Preferably, the biological sample is hair, and the environmental sample is sewage.

[0015] In the above-mentioned applications, the method for detecting the content of the psychoactive substance methcathinone in biological samples or sewage using the aforementioned isotope-labeled psychoactive substance compound includes the following steps: (1) Set the detection conditions for liquid chromatography-mass spectrometry; (2) Construction of the standard curve: Different proportions of methcathinone and methcathinone-... were added to the negative sample corresponding to the test sample. 13 C3 standard solution, after undergoing the same pretreatment steps as the test sample, was analyzed by LC-MS / MS to distinguish between methcathinone and methcathinone- 13 A standard curve was plotted using the peak area ratio and concentration of C3; wherein the internal standard is the isotopic drug-labeled compound.

[0016] (3) Pretreatment and determination of the test sample: The isotope psychoactive substance labeling compound is added to the test sample as an internal standard. After the same pretreatment steps as those used when plotting the standard curve, the sample is detected by LC-MS / MS to obtain the quantitative parameters of the test sample and the internal standard. The content of the test sample can be calculated by using the formula of the internal standard method standard curve.

[0017] Preferably, in step (1), the mobile phase for liquid chromatography-mass spectrometry detection is: A: acetonitrile, B: water (0.1% formic acid), gradient: 0 min 5% A, 7 min 90% A, 9 min 90% A, 9.1 min 5% A, 11 min 5% A; chromatographic column: Allure PFPP 2.1 x 100 mm 5 μm; column temperature: 40 ℃; flow rate: 0.4 mL / min; injection volume: 2 μL; ion source: electrospray ion source, positive mode (ESI+); spray voltage 4kV; ion source temperature: 300℃; collision gas: nitrogen.

[0018] Preferably, in step (2), the mass concentration of the internal standard in the mixed standard solution is 0.1%-99.9%.

[0019] Preferably, in step (3), the mass concentration of the internal standard in the sample to be tested is 0.1%-99.9%.

[0020] Preferably, in step (3), the formula for calculating the internal standard method is: X = (Y - b0) / b1; Where X is the concentration of the sample to be tested, Y is the peak area obtained by liquid chromatography-mass spectrometry, b0 is the intercept of the standard curve, and b1 is the slope of the standard curve.

[0021] Preferably, the mass content of the psychoactive substance methcathinone in the biological sample or the wastewater is 10. -9 %-10%.

[0022] The isotope-labeled psychoactive substance compound methcathinone provided by this invention 13 C3 can be used as an internal standard for determining the content of the psychoactive substance methcathinone in sewage samples. It can reduce the matrix effect of the samples and has good application prospects in forensic identification and other fields.

[0023] This invention proposes a carbon-13 labeled methcathinone standard, the technical breakthroughs of which include: Molecular structure consistency: The carbon-13 label is located at key sites on the benzene ring and alkyl chain, ensuring complete matching with the chemical properties, chromatographic retention time and fragment ion spectrum of natural methcathinone.

[0024] Isotope stability: Carbon-13 has no isotope exchange effect, which is superior to the hydrogen-deuterium exchange that may occur in deuterated internal standards during long-term storage or pretreatment; Application compatibility: It is compatible with multiple platforms such as LC-MS / MS and high-resolution mass spectrometry (HRMS), and can be used simultaneously as an internal standard for methcathinone, simplifying the analytical method development process.

[0025] When this labeled compound is used as an internal standard in IDMS, it can achieve the following: Improved sensitivity: Limit of detection (LOD) reaches 0.1 pg / mg (hair matrix), limit of quantitation (LOQ) ≤0.3 pg / mg; Accuracy optimization: Intra-batch / inter-batch coefficient of variation (CV) <3%, significantly better than existing alternative internal standards (CV 8–15%). Strengthening the validity of judicial evidence: Providing traceable data support that complies with ISO / IEC 17025 standards for drug enforcement and the construction of court evidence chains.

[0026] This invention fills the technological gap of methcathinone-specific isotope internal standards. Through the precise design and application of carbon-13 labeled standard substances, it promotes the development of psychoactive substance detection towards higher sensitivity, lower error, and stronger judicial credibility, which has significant social value for public safety and health management. Attached Figure Description

[0027] Figure 1 The methcathinone-1,2,3- protected by Boc in Example 1 13 EI mass spectrum of C-C3.

[0028] Figure 2 The methcathinone-1,2,3- in Example 1 13 C-C3 1 H-NMR spectrum.

[0029] Figure 3 The methcathinone-1,2,3- in Example 1 13 C3 13 C-NMR spectrum.

[0030] Figure 4 The methcathinone-1,2,3- in Example 1 13 High-resolution mass spectrum of C3.

[0031] Figure 5 This is a standard curve for detecting methcathinone content in wastewater in Example 2.

[0032] Figure 6 This is a standard curve for detecting the methcathinone content in hair samples in Example 3.

[0033] Figure 7A and Figure 7B The detection of methcathinone and methcathinone-1,2,3- in the wastewater sample in Example 2 are respectively. 13 Chromatogram for C3 detection.

[0034] Figure 8A and Figure 8BThe detection of methcathinone and methcathinone-1,2,3- in hair samples in Example 3 are respectively. 13 Chromatogram for C3 detection. Detailed Implementation

[0035] To better understand the technical content of this invention, the specific implementation method of this invention will be further described below.

[0036] In the description of this invention, "matrix effect" refers to the influence and interference of substances in the sample other than the analyte methcathinone on the analytical process and test results.

[0037] In the description of this invention, the mass concentration of methcathinone in hair is 10. -9 %-10%.

[0038] The present invention provides a carbon-13 labeled methcathinone isotope psychoactive substance labeling compound, 2-methylamino-1-phenyl-1-propanone-1,2,3- 13 C3, its structural formula is as follows, also denoted as methcathinone-1,2,3- 13 C3: .

[0039] The present invention will be further described below with reference to specific embodiments.

[0040] Example 1 Boc-protected methcathinone-1,2,3- 13 Preparation of C3 The carbon-13 labeled amino acid (DL-alanine-) was purified under nitrogen protection. 13C3 (CAS: 144476-54-0, 10 mmol), Boc2O, and sodium bicarbonate (20 mmol) were dissolved in 50 mL of anhydrous and oxygen-free THF and reacted at room temperature for 24 hours. After the reaction was complete, the mixture was extracted three times with diethyl ether, and the organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated. 35 mL of a 15% formaldehyde methanol solution was added to the concentrated solution, and the reaction was carried out at temperature T1 and time t1. Then, sodium cyanoborohydride (1.24 g, 20 mmol) was added at temperature T2 and time t2. The reaction was quenched with an aqueous ammonium chloride solution, and the mixture was extracted three times (40 mL each time) with ethyl acetate (EtOAc). The combined organic phases were washed with saturated sodium chloride solution, and the organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated to give the intermediate C13-labeled N-Boc-N-methylalanine. The obtained C13-labeled N-Boc-N-methylalanine was dissolved in dichloromethane (20 mL), and N,O-dimethylhydroxylamine hydrochloride (DMHH, 1.06 g, 10.9 mmol) and N-methylmorpholine (1.2 mL, 10.9 mmol) were added at -10 °C. 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI·HCl) (2.08 g, 10.9 mmol) was added in portions. The reaction was carried out at temperature T3 for time t3 hours. The reaction was quenched with 1 M hydrochloric acid (6.4 mL) at 0 °C. The organic phase was separated and extracted with dichloromethane (10 mL). The organic phase was washed with saturated sodium bicarbonate solution (6 mL). The saturated sodium bicarbonate aqueous phase was back-extracted with dichloromethane (10 mL). The combined dichloromethane phase was dried over anhydrous magnesium sulfate. The solvent was removed by filtration and vacuum distillation to obtain the intermediate C13-labeled N-methyl(S)-tert-butyl1-[(methoxymethyl)amino]-1-oxopropane-2-carboxamide.

[0041] Under nitrogen protection, 1 mmol of catalyst, 10 mmol of 1M phenyl magnesium bromide solution (10 mL), and 100 mL of solvent A were added to a two-necked flask. The reaction mixture was cooled to -35°C and stirred for about 30 minutes. 8.0 mmol of C13-labeled N-methyl-(S)-tert-butyl-1-[(methoxymethyl)amino]-1-oxopropane-2-carboxamide dissolved in 160 mL of solvent A was slowly added dropwise using a syringe. Stirring was continued at temperature T4 and reaction time t4, followed by standing at room temperature for 2 hours. The reaction was quenched with aqueous ammonium chloride solution and extracted three times with ethyl acetate (EtOAc) (40 mL each time). The combined organic phases were washed with saturated sodium chloride solution, the organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude product was purified by rapid column chromatography with basic alumina (n-hexane / ethyl acetate, 80:20) to obtain Boc-13C3-2-methylamino-1-phenyl-1-propanone, a pale yellow oil. The yields are shown in Table 1.

[0042] The product obtained under condition 11 above was characterized and confirmed structurally, as follows: EI-MS m / z: Calcd. for C 12 13 C3H 21 NO3[M]+ 266.2; Found: 266.2. Spectrum as shown. Figure 1 As shown.

[0043] Example 2 2-Methylamino-1-phenyl-1-propanone-1,2,3- 13 C3 preparation method.

[0044] Boc- 13 Crude C3-2-methylamino-1-phenyl-1-propanone (1 mmol) was dissolved in 25 mL of ethanol. The Boc protecting group was removed by treatment with hydrochloric acid-ethanol (10%) solution. After reacting at room temperature for 24 hours, TLC confirmed the disappearance of the starting material. The solution was adjusted to alkaline with potassium carbonate, and the mixture was extracted three times with diethyl ether. The combined organic phases were washed with saturated sodium chloride solution, and the organic layer was dried over anhydrous magnesium sulfate. The mixture was filtered and concentrated. The crude product was purified by rapid alkaline alumina column chromatography (n-hexane / ethyl acetate, 80:20) to give (2-methylamino-1-phenyl-1-propanone-1,2,3- 13 C3).

[0045] 1H NMR (600 MHz, DMSO-d6) δ 8.07 - 8.01 (m, 2H), 7.75 (t, J = 7.4 Hz,1H), 7.61 (t, J = 7.6 Hz, 2H), 5.35-5.25 (m, 0.5H), 5.10 - 5.01 (m, 0.5H), 2.59 (d, J = 3.9 Hz, 3H), 1.57 (dt, J = 7.2, 4.3 Hz, 1.5H), 1.35 (dt, J =7.2, 4.3 Hz, 1.5H). 13C NMR (151 MHz, dmso) δ 196.25(d), 134.59(s), 132.86(dd), 129.10(d), 128.72(d), 58.10(dd), 30.55(s), 15.31(d). HR-MS (ESI / TOF) m / z: Calcd. for C7 13C3H 14 NO [M+H] + 167.1176; Found: 167.1172. See spectrum. Figure 2 , 3, 4.

[0046] Example 3 With 2-methylamino-1-phenyl-1-propanone-1,2,3- 13 C3 is an isotopic internal standard used to detect the content of 2-methylamino-1-phenyl-1-propanone in wastewater.

[0047] (1) Liquid chromatography-mass spectrometry detection conditions: a) Instrument model: Shimadzu LCMS-8050; b) Column: Allure PFPP 2.1 x 100 mm 5 μm; c) Column temperature: 40 ℃; d) Mobile phase: A: acetonitrile, B: water (0.1% formic acid), gradient: 0 min 5% A, 7 min 90% A, 9 min 90% A, 9.1 min 5% A, 11 min 5% A; e) Flow rate: 0.4 mL / min; f) Injection volume: 2 μL; g) Ion source: Electrospray ion source, positive mode (ESI+); h) Spray voltage 4 kV; i) Ion source temperature: 300℃; j) Collision gas: Nitrogen.

[0048] The ion pairs and corresponding conditions are shown in Table 2: (2) Sample pretreatment The wastewater sample was filtered through filter paper. 100 mL of the sample was then added to 2 mL of methanol (containing 10 ng / mL of 2-methylamino-1-phenyl-1-propanone-1,2,3-methylpropanone). 13 C3), each 50 mL sample was loaded onto an SPE column at a rate of 5 mL / min. After loading, the sample was first eluted with 5 mL of methanol, and then eluted with 5 mL of 5% ammonia-acetonitrile solution. The eluent was evaporated to dryness under airflow in a 40°C water bath, redissolved with 80 μL of methanol, filtered through a 0.22 μL filter membrane, and 2 μL was injected into LC-MS / MS for analysis. Figure 7A and 7BThe spectrum shown is shown. The quantitative ion pair is 164.2 / 131.2, and the two detections of 2-methylamino-1-phenyl-1-propanone and the internal standard 2-methylamino-1-phenyl-1-propanone-1,2,3- 13 The peak area ratio of C3 is 24425 / 42712, 38914 / 56141.

[0049] (3) Plotting the standard curve Add 20 μL of methanol (containing 25 ng / ml 2-methylamino-1-phenyl-1-propanone-1,2,3-) to 50 mL of negative wastewater sample. 13 C3), 20 μL of 2-methylamino-1-phenyl-1-propanone standard reference was added to prepare wastewater spiking samples with concentrations of 0.5, 1.0, 2.0, 5.0, 10, and 100 ng / L. Three replicates were prepared for each concentration. The samples were vortexed for 3 min, allowed to stand at room temperature for 30 min, and then processed according to the sample pretreatment procedure before LC-MS / MS analysis. The analysis focused on the analysis of 2-methylamino-1-phenyl-1-propanone and 2-methylamino-1-phenyl-1-propanone-1,2,3- 13 A standard curve was plotted using the peak area ratio and concentration of C3 to obtain the following results: Figure 5 The diagram shown.

[0050] The standard curve formula is Y = (0.462642)X + (0.115575), where X is the concentration of the sample to be tested, Y is the peak area obtained by liquid chromatography-mass spectrometry, b0=0.115575 is the intercept of the standard curve, and b1=0.462642 is the slope of the standard curve.

[0051] Based on the quantitative relationship between peak area ratio and concentration in the standard curve, and according to the calculation formula: ; The content of 2-methylamino-1-phenyl-1-propanone in the sample was calculated to be 11.4 ng / L.

[0052] Example 4 With 2-methylamino-1-phenyl-1-propanone-1,2,3- 13 C3 is an internal standard for detecting the content of 2-methylamino-1-phenyl-1-propanone in hair.

[0053] (1) Liquid chromatography-mass spectrometry detection conditions: same as in Example 3.

[0054] (2) Sample pretreatment and detection Hair samples were washed with ultrapure water, detergent solution, and acetone, dried, and then shredded. Each shred was weighed 20.0 mg and mixed with 1 mL of methanol (containing 10 ng / mL 2-methylamino-1-phenyl-1-propanone-1,2,3-ethylhexylene). 13 C3), after grinding, was sonicated in a cryo-ultrasound machine for 30 min, centrifuged at 4000 r for 5 min, and 800 μL of the supernatant was collected and evaporated to dryness under airflow in a 60℃ water bath. The supernatant was then redissolved in 80 μL of methanol, filtered through a 0.22 μL filter membrane, and 5 μL was injected into LC-MS / MS for analysis, yielding the following results: Figure 8A and Figure 8B The spectrum shown is shown. The quantitative ion pair is 164.2 / 131.2, and the two detections of 2-methylamino-1-phenyl-1-propanone and the internal standard 2-methylamino-1-phenyl-1-propanone-1,2,3- 13 The peak area ratios of C3 are 1840895 / 1259356 and 1464049 / 1206492.

[0055] (3) Plotting the standard curve Blank negative hair samples were washed with ultrapure water, detergent solution, and acetone, dried, and then shredded. Each shred was weighed 20.0 mg and mixed with 1 mL of methanol (containing 10 ng / mL 2-methylamino-1-phenyl-1-propanone-1,2,3- ). 13 C3), add 20 μL of 2-methylamino-1-phenyl-1-propanone standard reference at concentrations of 0, 100, 200, 400, 1000, 2000, 10000, and 20000 ng / ml to prepare hair samples with concentrations of 0, 0.1, 0.2, 0.4, 1.0, 2.0, 10, and 20 ng / mg. Prepare three replicates for each concentration. Vortex for 3 min, allow to stand at room temperature for 30 min, and then process according to the sample pretreatment procedure. Analyze by LC-MS / MS to detect the 2-methylamino-1-phenyl-1-propanone and 2-methylamino-1-phenyl-1-propanone-1,2,3- 13 A standard curve was plotted using the peak area ratio and concentration of C3 to obtain the following results: Figure 6 The diagram shown.

[0056] The standard curve formula is Y = (1.33436)X + (-0.0647420), where X is the concentration of the sample to be tested, Y is the peak area obtained by liquid chromatography-mass spectrometry, b0 = -0.0647420 is the intercept of the standard curve, and b1 = 1.33436 is the slope of the standard curve.

[0057] Based on the quantitative relationship between peak area ratio and concentration in the standard curve, and according to the calculation formula: ; The content of 2-methylamino-1-phenyl-1-propanone in the sample was calculated to be 1.0 ng / mg.

[0058] The isotope-labeled psychoactive substance marker compound provided by this invention, when detecting the psychoactive substance 2-methylamino-1-phenyl-1-propanone in a sample, can be added to the sample in an appropriate amount of the isotope-labeled psychoactive substance marker compound 2-methylamino-1-phenyl-1-propanone-1,2,3- 13 C3, after appropriate pretreatment according to the detection requirements, is detected by liquid chromatography-mass spectrometry (LC-MS / MS). The isotope-labeled psychoactive substance compound is used as an internal standard. In multiple reaction monitoring (MRM) mode, the qualitative and quantitative detection of the analyte is achieved by comparing the peak area ratio of the target substance and the analyte. The detectable psychoactive substance is 2-methylamino-1-phenyl-1-propanone, which has high specificity and high sensitivity.

[0059] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the present invention as claimed. The scope of protection of this invention is defined by the appended claims and their equivalents.

[0060] In this specification, the invention has been described with reference to specific embodiments thereof. However, it will be apparent that various modifications and variations can be made without departing from the spirit and scope of the invention. Therefore, the specification and drawings should be considered illustrative rather than restrictive.

Claims

1. A carbon-13 labeled psychoactive substance, characterized in that, The chemical structural formula is: 。 2. A method for preparing a carbon-13 labeled psychoactive substance as described in claim 1, characterized in that, Including the following steps: (1) 13 C-C3-alanine is converted to N-methyl-N-Boc- by Boc2O and a methylating agent. 13 C-C3-alanine; (2) The product obtained in step (1) is reacted with N,O-dimethylhydroxylamine to obtain an intermediate; (3) The intermediate obtained in step (2) is reacted with a phenyl nucleophile to obtain 13 C-C3-2-N-Boc-methylamino-1-phenyl-1-propanone; (4) The product obtained in step (3) is subjected to a Boc protecting group removal reaction to obtain the carbon 13 labeled methcathinone.

3. The method for preparing carbon-13 labeled psychoactive substances according to claim 2, characterized in that, In step (1), the methylating agent is formaldehyde. 13 C-C3-alanine first reacts with Boc2O, then with formaldehyde at 20°C to 30°C for 20 to 28 hours, and finally with sodium cyanohydride at 20°C to 30°C for 44 to 52 hours. In step (2), the reaction time is 10 to 14 hours and the reaction temperature is -5°C to 5°C; In step (3), the catalyst is CuI, the solvent is THF, the phenyl nucleophile is phenyl magnesium bromide, the reaction time is 10 to 14 hours, and the reaction temperature is -5℃ to 5℃.

4. The use of the carbon-13 labeled psychoactive substance of claim 1 or the carbon-13 labeled psychoactive substance prepared by the preparation method of claim 2 in detecting the content of methcathinone in biological or environmental samples.

5. The use according to claim 4, characterized in that, The carbon-13 labeled psychoactive substance was used as an isotopic internal standard.

6. The use according to claim 4, characterized in that, The biological sample is hair, and the environmental sample is sewage.

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