Application of Deuterated Internal Standard in Toxicological Analysis in Court

At present, the quality control system of the Tribunal's Toxicology Analysis Laboratory is becoming more and more perfect and the requirements are getting higher and higher. At the same time, with the gradual improvement of the judicial system, the awareness of citizen evidence has increased, and more and more attention has been paid to the quality of case identification conclusions. Therefore, the quality control of toxicant analysis is very important and is increasingly valued by toxic analysts.

To monitor the reliability of toxicant analysis methods, the method of adding internal standards is commonly used internationally, that is, the internal standard method. In order to obtain rigorous and accurate analysis results when selecting internal standards, the best internal standard is the deuterated standard of each toxicant, and has broad application prospects in toxicant analysis. However, the internal standards sold in the domestic market are all foreign products of the agency, which are expensive, and are not sold for every analyte. Therefore, the development of the standard of deuterium used in the analysis of the toxicology of the court will fill the gap in the development of China's modern standard in the field, and further improve the quality control of toxicological analysis in China.

1 Quality control of the toxic analysis of the court and the internal standard of the deuterium

At present, the rapid development of toxicant analysis technology has evolved from qualitative analysis to quantitative analysis, from constant to micro and ultra-micro analysis. It is not only limited to the qualitative determination of gastric contents, but also determines whether the poisons in the body are negative or positive through the qualitative and quantitative determination of trace toxicants and metabolites in body fluids and tissues; if it is positive, it is necessary to further determine the amount of toxic or lethal dose. . There are many factors affecting the results of toxicological analysis, and the correct analysis or not plays a direct evidence role in poisoning cases. Shanghai Chuangsai provides: 氘代正辛-d18, 17252-77-6, D, 99%, commodity number: C16-O10200-1g, price 1198 yuan

As the quality control method of the poison analysis method, there are an external standard method and an internal standard method. The external standard method is to add standard monitoring and analysis process and results to blank samples. The external standard method requires strict control of the entire operation process, otherwise it will cause analysis errors. The internal standard method is to monitor the method of adding the internal standard to the sample to be tested, which reduces the influence of many objective factors. The addition of internal standards is commonly used internationally to ensure the reliability of analytical methods, which have higher accuracy and precision. This monitoring method can avoid the occurrence of false negatives in the toxicant analysis due to the difference in the addition of the matrix and the parallel operation. Qiu Jingying et al. compared the results of high performance capillary electrophoresis internal standard method and external standard method. The results show that the results of external standard method are lower than the internal standard method. The high performance capillary electrophoresis internal standard method is better than the external standard method. . Yang Xiaoyu used the finished beer as a sample. After distilling the beer, he used a gas chromatograph to quantitatively analyze the higher alcohol in the beer by external standard method and internal standard method to compare the advantages and disadvantages of the two quantitative methods. The results show that: Under normal circumstances, the internal standard method is more accurate than the external standard method. Wu Yan et al. pointed out how to choose the internal standard method or the external standard method. For the conditions that the precision requirements are relatively high and the accuracy of the results will have a significant impact, the internal standard method is first selected. In order to obtain the most rigorous and accurate analysis results when using the internal standard method, the best internal standard is the deuterated standard of each poison.

In China, the use of stable isotope 2H(D) labeled organic deuteration standards with the same molecular structure as the poison to be tested, as an internal standard analysis method, has become the development trend of strict quality control of poison analysis in the forensic science field. The use of the isotope 2H(D)-labeled compound as an internal standard avoids the effects of complex matrix effects, pretreatment and mass spectrometry detectors on the results of analytical methods, and effectively corrects errors in the method. Significantly improve the recovery rate of the target compound and the stability of the method, which can greatly improve the qualitative and quantitative accuracy of the analytical method.

2 Application of deuterated internal standard

In foreign countries, toxicant analysis workers generally use the deuterated internal standard added with the tested poison to control the quality of the analytical method. The maternal product is an internal standard, and the matrine is detected by liquid-liquid extraction and gas chromatography-mass spectrometry. The results show that the linear range of matrine is 10 to 500 ng / mL, and the daytime and intraday precision are 0.4. % ~4. 0%, 1. 0% ~ 3. 5%, the limit of quantification is 23 ng / mL. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the determination of lapatinib in human blood. When using the internal standard method for quantification, the authors performed non-isotopic and isotopically labeled internal standards. Comparison, the results show that: Deuterated lapatinib has the closest physical and chemical properties to lapatinib. Adding deuterated lapatinib before extracting blood samples can correct the lapatinib caused by sample purification. Loss; at the time of detection, since the effects of the eropabinib and lapatinib interfered with the components are almost identical, the inhibition or enhancement of the lapatinib ion by the interfering component during mass spectrometry ionization can be corrected, thereby More accurate measurement results were obtained. Shanghai Chuangsai provides: lapatinib base, 231277-92-2, >98.5%, can be used for cell culture, commodity number: C84-1463-100MG, price 380 yuan

As an isotope internal standard, the LC-MS/MS analysis method of carvedilol in human blood was established, and the use of deuterated internal standard can effectively reduce or eliminate the matrix effect in liquid chromatography-mass spectrometry. The isotope internal standard is the preferred internal standard for eliminating the matrix effect. The isotope internal standard has the same chemical properties and the same retention time as the target, so it can offset the matrix effect during mass spectrometry ionization and eliminate the difference in the pretreatment process. . Comparing the samples with the addition of triamcinolone acetonide to 20 tissues, the relative standard deviation of the signal intensity when using the fluorohydrocortisone as the internal standard was 32.6%, using the isotope internal standard acetamidine-D6. The relative standard deviation can be reduced to 5.7%.

At present, there are no commercial products in China that have been involved in the poisoning of internal standards, and the forensic science field is in urgent need of such substances for the quality control of poison analysis. However, due to the foreign technology monopoly, the internal standard reagents of the Sui Dynasty are all dependent on imports. The developed countries have formed a high-tech industry with significant economic benefits in the preparation of the internal standard reagents of the Sui Dynasty, with a relatively complete technology and industrial chain. Due to technical secrecy and product monopoly, the technical literature and patents on synthesis have hardly been reported. At the same time, unlike the poisons in developed countries, which are concentrated in drug abuse and therapeutic drugs, China also includes a large number of poisons with regional characteristics such as pesticides, rodenticides and Chinese herbal medicines, and the internal standards of such poisons are in foreign and domestic markets. blank. Therefore, the preparation of deuterated internal standard reagents with independent intellectual property rights, reducing the dependence on foreign reagents and breaking the foreign blockade can not only promote the rapid development of the toxic analysis in China, but also create considerable economic benefits and society. benefit.

3 Development of the internal standard of the Sui Dynasty in China

In recent years, the domestic development of the internal standard materials in the Sui Dynasty has made some progress, and has developed sulfamethoxazole-D4 and sulfaquinoxaline-D4 as the internal standard for the detection of sulfonamide residues and Sudan Red I-D5 As an internal standard reagent for the detection of food safety Sudan Red series of banned dyes. In the field of forensic science, the Ministry of Public Security's physical evidence appraisal center has successfully developed four kinds of benzodiazepine anti-sedative drugs, which have good stability in practical applications and laid a foundation for quality control of forensic toxic analysis. basis. However, the preparation of the above-mentioned deuterated internal standard is currently limited to the laboratory level, and it is urgent to expand the production scale to further improve the stability and output rate. At the same time, it is necessary to gradually expand the types and scope of the development of internal standards, and gradually realize the coverage of the whole field. And application. Shanghai Creations offers: Sudan Red III, 85-86-9, Solvent Red 23, item number: C84-1857-25G, price 48 yuan

The deuterated internal standard of the poisons involved in the case has a wide range of application value in the field of quality control of toxicant analysis, and the high price and incomplete variety of imported internal standard materials have become the bottleneck restricting the evaluation of toxicological methods, and the analysis of poisons in domestic cases. Quality control has brought about a very passive situation. Prepare the internal standard of detoxification of the poisons involved in the case, and establish national standards and industry standards for the analysis and testing using the internal standard of deuteration, and apply them to the toxicological analysis department of the judicial departments at all levels in China, and vigorously improve the energy level of the toxicological analysis technology and accelerate The pace of integration with the international advanced. The localization of the internal standard of the Sui Dynasty will fill the gap in the domestic professional field, break the situation of foreign reagents and its expensive price monopolizing the domestic market, and at the same time reduce the cost of scientific research and application, and carry out strict quality control on the toxicological analysis methods in the forensic science field. And lay a solid foundation for comprehensively improving the level of toxic analysis in China.

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