Liquid chromatogram-mass spectrum detection method of drugs and mental disease resistant drugs in blood

A technology of mental illness and mass spectrometry, applied in measurement devices, instruments, scientific instruments, etc., can solve problems such as being unsuitable for large sample detection, complex operation, and affecting the efficiency of medical certificate issuance.

Active Publication Date: 2018-03-16
中国民用航空局民用航空医学中心
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AI Technical Summary

Problems solved by technology

[0005] At present, there are more than 30,000 active pilots in China, and there are also a large number of flight students, foreign pilots, and military-to-civilian pilots. Facing such a large-scale test object, aviation medical inspection needs to be based on the large number of test objects and the limited detection time (too long) The detection cycle will affect the efficiency of the issuance of medical certificates, and will also expand the potential risk of the blank period before the test results come out), the amount of biological samples is small, and there are many target compounds to be detected, so a fast, easy, sensitive and reliable detection method can be established
[0006] In 2010, the Judicial Authentication Administration of the Ministry of Justice of the People's Republic of China issued the judicial authentication technical specification of "Detection of 154 Poisons (Drugs) in Blood and Urine by Liquid Chromatography-Tandem Mass Spectrometry" (SF / Z JD0107005-2010), In this specification, the sample pretreatment adopts the organic solvent extraction method, which is complex in operation and requires a large amount of blood or urine. It is not suitable for large sample testing, and cannot meet the rapid and sensitive needs of civil aviation crew safety drug supervision and testing.
In 2011, Sun Yingying et al. (“Determination of 11 Opioid Alkaloids in Hair by Liquid Chromatography-Tandem Mass Spectrometry”, Acta Pharmaceutica Sinica, 2011, 46(12): 1501-1506) proposed a method that can simultaneously detect 11 opioid alkaloids in hair. Liquid chromatography-tandem mass spectrometry detection method for alkaloids, this method uses hair as a biological sample, the sample processing method is complicated, and the generalization is not high; and the detection method in this document does not involve the detection of antipsychotic drugs It is also difficult to use for rapid detection of large samples
This method has high sensitivity and strong specificity, but because the tested object does not contain antipsychotic drugs, and the biological samples are mainly hair, the sample processing method is complicated, and it is also not suitable for rapid detection of large samples, and cannot meet the needs of civil aviation personnel. The need for drug safety regulation
In 2010, Zhang Xiuyao et al. ("Ultra-high performance liquid chromatography-tandem mass spectrometry simultaneously and rapidly confirm the detection of 42 psychotropic drugs and their metabolites in plasma and urine", Chromatography, 2010, 28(1): 23-33) proposed An ultra-high performance liquid chromatography-tandem mass spectrometry method for the simultaneous rapid detection of 42 psychotropic drugs and their metabolites in plasma and urine, including antidepressants, antiepileptic drugs, antipyretic analgesics, etc. , but does not involve drugs, this method cannot meet the inspection needs of civil aviation crews for drugs and prohibited drugs
[0007] At present, there is no effective method reported in the literature that can quickly and sensitively detect a variety of common drugs and antipsychotic drugs at the same time, and there is even a lack of fast, easy, sensitive, reliable, reproducible and accurate methods that can be used in pilots' drug use. Method for detecting narcotics and antipsychotics in blood

Method used

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  • Liquid chromatogram-mass spectrum detection method of drugs and mental disease resistant drugs in blood
  • Liquid chromatogram-mass spectrum detection method of drugs and mental disease resistant drugs in blood
  • Liquid chromatogram-mass spectrum detection method of drugs and mental disease resistant drugs in blood

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Experimental program
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Effect test

Embodiment 1

[0201] Embodiment 1 Detection of the establishment of the target compound and the basic properties of the compound

[0202] According to the regulations on narcotics and prohibited drugs in the "Civil Aviation Personnel Physical Examination Certificate Management Rules" (CCAR‐67FS‐R2) and "Airline Crew and Air Traffic Controller Physical Examination Appraisal" (AP‐67FS‐002), and passed the approval of Peking University Consultation and research by clinicians of the Sixth Hospital and airline doctors, combined with the "Guidelines for the Prevention and Treatment of Psychiatric Diseases in China", finally screened 23 common drugs and antipsychotic drugs as target compounds. These 23 common drugs and antipsychotic drugs The drug classes and their associated chemical properties are shown in the table below.

[0203] Table 14 List of chemical properties of target compounds

[0204]

[0205]

[0206]

Embodiment 2

[0207] Example 2 Reagents and Instruments

[0208] 1. Reagents

[0209] Unless otherwise specified, the reagents are all analytically pure, and the water is the first-grade water specified in GB / T 6682. Morphine, codeine, 6-monoacetylmorphine, amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), ketamine , heroin, citalopram, paroxetine, clonazepam, sertraline, amitriptyline, venlaxine, chlorpromazine, fluoxetine, estazolam, diazepam, mianserin, Fluvoxamine, alprazolam, maprotiline reference substances, purity ≥ 97%. Methanol (GR); trichloroacetic acid (GR); formic acid (excellent grade); deionized water was prepared by an ultrapure water meter (Millipore pure water system).

[0210] 2. Instrument

[0211] Ultra-high performance liquid chromatography / triple quadrupole mass spectrometer (TQD UPLC‐MS, Waters Co., Ltd., USA); adjustable pipette (eppendorf); SIGMA 3‐18K desktop high-speed refrigerated centrifuge (Germany)...

Embodiment 3

[0214] Example 3 Blood sample pretreatment

[0215] Centrifuge the anticoagulated blood to be tested at 5000rpm for 3min, take 200μL of the supernatant into a 1.5mL centrifuge tube, add 5μL of sulfamethoxazole SMZ (internal standard) with a concentration of 0.1μg / mL, mix well, and then add 80μL of 10% trichloroacetic acid , vortexed for 1 min, centrifuged at 12,000 rpm for 15 min, and the supernatant was taken for inspection.

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Abstract

The invention provide a ultra-performance liquid chromatogram-mass spectrum detection method for 23 types of drugs and mental disease resistant drugs in blood. The method comprises the following steps: 1) sample processing: employing an organic solvent for processing a sample through protein sediment; 2) primary screening detection: employing a ultra-performance liquid chromatogram-tandem mass spectrum (UPLC-MS/MS) multi-reaction monitoring (MRM) mode for primary screening detection; and 3) employing the ultra-performance liquid chromatogram-tandem mass spectrum (UPLC-MS/MS) multi-reaction monitoring (MRM) mode for reinspection of the positive sample through the primary screening in the step 2). According to physical and chemical properties of 9 types of drugs and 14 types of mental disease resistant drugs, during reinspection, the UPLC-MS/MS detection condition which is different with the primary screening detection is employed, different sample pretreatment methods are employed, so that the detection method can satisfy the rapid, sensitive and accurate requirements of primary screening detection, and misjudgement of false positive results can be reduced.

Description

technical field [0001] The invention relates to a method for detecting drugs and antipsychotic drugs in blood by ultra-high performance liquid chromatography-mass spectrometry, and belongs to the technical field of medical testing. Background technique [0002] Flight safety is a major issue related to the national economy and the people's livelihood. Pilots belong to a special occupational group with high safety requirements in the industry. Their mental and psychological health is one of the important prerequisites to ensure the safety of civil aviation transportation. [0003] Drugs and prohibited drugs endanger the physical and mental health of personnel in civil aviation safety-sensitive positions and affect flight safety. In April 2015, the National Narcotics Control Office notified a case of cargo pilots taking drugs and requested the Civil Aviation Administration to carry out relevant anti-drug work to prevent major flight safety accidents. In March 2015, the crash ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02G01N30/72
CPCG01N30/02G01N30/72
Inventor 李清艳王伟刘国如许海山乔湜刘永锁丁仁奎于红燕郭丹名
Owner 中国民用航空局民用航空医学中心
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