CN105572241B - The method for determining amphetamine in blood and urine, ketamine, pethidine and methadone - Google Patents
The method for determining amphetamine in blood and urine, ketamine, pethidine and methadone Download PDFInfo
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- CN105572241B CN105572241B CN201410619166.1A CN201410619166A CN105572241B CN 105572241 B CN105572241 B CN 105572241B CN 201410619166 A CN201410619166 A CN 201410619166A CN 105572241 B CN105572241 B CN 105572241B
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Abstract
The invention belongs to technical field of analytical chemistry, is related to a kind of for detecting 4 kinds of amphetamines (amphetamine, crystal methamphetamine, methylene dioxamphetamine, methylene benzylene chloride propylamine), ketamine, pethidine, methods of methadone in quick measure blood and urine.This method high sensitivity, high specificity, the range of linearity are wide, available for unknown concentration determinand qualitative in blood and urine and quantitative, and it is simple to operate, quick, the process volatilized need not be extracted, disclosure satisfy that judicial expertise task it is urgent, to detection time require it is high the characteristics of.The detection architecture of the present invention provides new technology platform, application easy to spread for illicit drugs inspection.
Description
Technical field
The invention belongs to analytical chemistry field, and in particular to amphetamine, ketamine, piperazine replace in one kind measure blood and urine
Pyridine and the method for methadone.This method easy can quickly determine 4 kinds of amphetamines (amphetamine, methylbenzenes third in blood and urine
Amine, methylene dioxamphetamine, methylene benzylene chloride propylamine) compound such as ketamine, pethidine and methadone, it is especially suitable
For judicial expertise field.
Background technology
According to data, the drugs abused extensively at present include 4 kinds of amphetamine compound (amphetamines
(amphetamine, AMP), crystal methamphetamine (methamphetamine, MAMP), methylene dioxamphetamine
(methylenedioxyamphetamine, MDA), methylene benzylene chloride propylamine
(methylenedioxymethamphetamine, MDMA), and ketamine and pethidine.
Based on studies have shown that AMP and MAMP its toxicity is mainly acted on central nervous system stimulant；MDA, MDMA have concurrently emerging
Put forth energy and hallucinogenic action, be known as the main component of dancing outreach drugs.Ketamine has hallucinogenic action, length also referred to as " KET "
Phase, which uses or is excessively used, to cause permanent damage to brain；Pethidine also known as meperidine, it is clinical conventional analgestic, for a long time
Using dependence can be produced, the drugs of strict supervision are listed in China；Methadone is given up because its pharmacological action is similar to morphine
Symptom is lighter, relies on the choice drug for carrying out substituting diminishing method drug addiction treatment for opium drugs such as heroin, therefore be involved in drug traffic
There is higher recall rate in the identification of case.
Judicial expertise practice display, blood and urine are biological materials mostly important in drugs identification；Wherein, in urine
The concentration of drugs is high, and therefore, urine is that sample is often used in drugs qualitative analysis；Blood is the conventional sample of drugs quantitative analysis, institute
The quantitative value obtained can be compared with the poisoning concentration of document report or lethasl concentration.
Amphetamine, ketamine, pethidine, the method for methadone are usual in the disclosed measure blood of prior art and urine
There are ELISA, gas chromatography-mass spectrometry, Liquid Chromatography-Mass Spectrometry etc..Practice display, described is enzyme-linked
Immunization specificity is poor, it is difficult to specification configuration analog, often there is the situation of false positive, thus, a kind of primary dcreening operation can only be used as
Means, it is necessary to further confirmed using gas chromatography-mass spectrometry or Liquid Chromatography-Mass Spectrometry, and
Biological sample is carried out before gas chromatography-mass spectrometry or Liquid Chromatography-Mass Spectrometry analyzed, is required to pair
Sample is extracted and purified, and the step is related to the process for volatilizing extract solution, thus often produce and research has shown that, AMP
Quickly volatilized with volatilizing for extract solution with MAMP, the reappearance of impact analysis and standard curve it is linear, cause biological inspection
Analyte is difficult to the defects of accurate quantitative analysis described in material.There is researcher to enter by acid adding or using under cryogenic conditions to sample
Row is volatilized or operated by derivatization to avoid AMP and MAMP volatilization, but used method is cumbersome and time-consuming, is still difficult to
Meet judicial expertise for the quick requirement of drugs of abuse.
Present inventor is directed to current present situation, intends providing a kind of easy, quick and accurately determining blood simultaneously
With 4 kinds of amphetamines (amphetamine, crystal methamphetamine, methylene dioxamphetamine, methylene benzylene chloride propylamine) in urine,
Ketamine, pethidine, the method for methadone content.
The content of the invention
The purpose of the present invention is the defects of overcoming prior art, there is provided amphetamine, chlorine in one kind measure blood and urine
The method of amine ketone, pethidine and methadone；It is especially a kind of easy, quick and can accurately determine simultaneously 4 in blood and urine
Kind amphetamine (amphetamine, crystal methamphetamine, methylene dioxamphetamine, methylene benzylene chloride propylamine), ketamine, piperazine
For pyridine, the method for methadone content.This method can meet judicial expertise for the quick requirement of drugs of abuse.
Specifically, the inventive method uses gas chromatography-mass spectrometry to 4 kinds of amphetamines, chlorine in blood and urine
Amine ketone, pethidine, methadone carry out qualitative and quantitative analysis.In this method, alkali is passed through to a small amount of blood and urine (0.2-1mL)
After change processing, add a small amount of organic solvent (1-chlorobutane, 100-300 μ L) and carry out liquid-liquid extraction, transfer upper layer of extraction liquid is direct
It is measured (the μ L of sample size 2) using gas chromatography-mass spectrometry, you can determine the content of analyte.
The pretreatment process of the inventive method sample is easy, quick, easy to spread；The present invention uses HP-5MS capillary gas phases
Chromatographic column and mass detector, 4 kinds of amphetamines, ketamine, pethidine, the content of methadone in blood and urine are determined,
The high sensitivity of detection, the degree of accuracy are good.
More specifically, the side for determining amphetamine in blood and urine, ketamine, pethidine and methadone of the invention
Method, it is characterised in that extract solution is directly measured using gas chromatography-mass spectrometry, is comprised the steps：
(1) blood or urine sample are pre-processed
Blood or urine sample are taken, adds internal standard, 10%NaOH solution is added and sample is adjusted to strong basicity, add 1- chlorine
Butane, vortex mixed 2min, 10000rpm centrifugation 5min, shifts upper organic phase；
(2) using 4 kinds of amphetamines, ketamine, piperazines in gas chromatography/mass spectrometry blood or urine sample
For pyridine and the concentration of methadone；Chromatographic column is HP-5MS capillary columns.
In the present invention, only a small amount of blood or urine sample sample need to be taken to be pre-processed, be taken in embodiments of the invention
0.2-1mL blood or urine sample sample is pre-processed；
In the present invention, internal standard MAMP-D5 is added in blood or urine sample sample, in blood in embodiments of the invention
Or internal standard MAMP-D5 0.2-1 μ g are added in urine sample sample, add 10%NaOH solution and sample is adjusted to strong basicity；
In the present invention, 1-chlorobutane is used not to be related to and carry as Extraction solvent in blood and urine sample pretreatment operation
Take the process that volatilizes of liquid, added in embodiments of the invention 1-chlorobutane 100-300 μ L, vortex mixed 2min, 10000rpm from
Heart 5min, shift upper organic phase；
In the present invention, after adding 1-chlorobutane, be not related to extract solution volatilizes process, by extract solution direct injected gas phase color
Spectrum-GC-MS is detected；
In the present invention, the chromatographic column used is HP-5MS capillary columns (30m × 0.25mm × 0.25 μm), the μ L of sample size 2.
The present invention has carried out qualitative and quantitative to 4 kinds of amphetamines, ketamine, pethidine, methadone in blood and urine
Analysis, as a result accurately, reliably；Each compound test limit is 5ng/mL, is quantitatively limited to 20ng/mL, the μ of the range of linearity 0.02~25
G/mL, linearly dependent coefficient r values are all higher than 0.99.For blood sample, extraction recovery is accurate in the range of 33.7-80.5%
Exactness is in the range of 87.1-113.9%, and the RSD values of withinrun precision are no more than 10.2%, and the RSD values of betweenrun precision do not surpass
Cross 12.1%；For urine sample, extraction recovery is in the range of 64.6-112.6%, and the degree of accuracy is in 85.1-108.4% scopes
Interior, the RSD values of withinrun precision are no more than 6.3%, and the RSD values of betweenrun precision are no more than 11.5%.
Table 1 is the chromatographic retention and mass spectral characteristic peak of detection object.
Table 1
The inventive method is compared with the method for prior art with following clear superiority：
(1) compared with ELISA, the high sensitivity of the inventive method, the test limit of each compound can reach 5ng/
ML, and the detection of ELISA is limited to 300-1000ng/mL.And for the detection of drugs, current way is first in the world
Primary dcreening operation is carried out with ELISA, then is confirmed with gas chromatography-mass spectrometry or Liquid Chromatography-Mass Spectrometry,
Thus the sensitivity of the inventive method is sufficient for the needs of actual inspection case in judicial expertise work.
(2) compared with the gas chromatography-mass spectrometry of prior art or Liquid Chromatography-Mass Spectrometry, the present invention
Method greatly simplifies the pre-treatment step of sample；The method of prior art is both needed to the process of the extract solution drying of sample,
Take longer (more than 30min), and be difficult to avoid that 2 kinds of important amphetamine material (AMP and MAMP) waving with extract solution
Hair and lose, carry out impact analysis reappearance and standard curve it is linear, cause 2 kinds of materials of this in biological material to be difficult to accurately
It is quantitative；Though having researcher by acid adding or using being volatilized to sample under cryogenic conditions or operated by derivatization to keeping away
Exempt from AMP and MAMP volatilization, but these methods are cumbersome and time-consuming, it is difficult to meet that judicial expertise quickly will for drugs of abuse
Ask；The step of the inventive method sample pre-treatments, avoids the process of drying, is not required to other sample handling procedures, ensure that standard
Curve it is linear, it is ensured that the accuracy of quantitative result；Simultaneously easy, quick (time for sample pretreatment is within 10min), can show
Write the efficiency that ground improves drugs identification.
(3) the inventive method uses whole blood sample amount is few (can as little as 0.2mL, prior art 0.95-2mL), can
Tackle the generally very limited amount of situation of sample amount in legal medical expert's case.
(4) consumption of organic solvent that the inventive method uses is few (100-300 μ L, prior art 1.5-5mL), to operation
The health harm of personnel is small, more friendly to environment, can save analysis cost.
Brief description of the drawings
Fig. 1 is the reference colour spectrogram of 4 kinds of amphetamines, ketamine, pethidine, methadone,
Wherein, AMP (3.6min), MAMP (4.0min), MDA (5.8min), MDMA (6.1min), pethidine
(7.2min), ketamine (7.7min) and methadone (8.8min) and internal standard compound MAMP-D5 (4.0min).
Embodiment
Embodiment 1
The chromatographic condition of use：
Chromatographic column：HP-5MS elastic quartz capillary tube gas chromatographic columns, 30m × 0.25mm × 0.25 μm
Column temperature：100℃(1.5min)—25℃/min—280℃(15min)
The solvent delay time：3min
Injection port/transmission line temperature：250℃/280℃
Carrier gas：High-purity He, constant current 1mL/min
EI sources electron energy：70Ev
Scan mode：Salbutamol Selected Ion Monitoring (SIM)
Sample size：2μL
Detect the chromatographic retention and mass spectral characteristic peak of object：As shown in table 1.
Sample preparation：
(1) extraction of blood sample
Blood sample 0.2-1mL is taken, adds internal standard (MAMP-D5) 0.2-1 μ g, 10%NaOH solution 0.05mL is added and mixes
It is even, add 1-chlorobutane 100-300 μ L, vortex mixed 2min, 10000rpm centrifugation 5min, transfer upper organic phase 50-100
μ L analyze for GC-MS；
(2) extraction of urine sample
Urine sample 0.2-1mL is taken, internal standard (MAMP-D5) 0.2-1 μ g is added, pH is adjusted to using 10%NaOH solution>11,
Add 1-chlorobutane 100-300 μ L, vortex mixed 2min, 10000rpm centrifugation 5min, transfer upper organic phase 50-100 μ L
Analyzed for GC-MS；
Linear test：
Hybrid standard series of working liquids is taken, adds blank whole blood and urine, is vortexed and mixes, is made into and distinguishes containing testing concentration
For 0.02,0.05,0.1,0.5,1,5,10,25 μ g/ml standard plasma containing drug and urine, by being operated under " sample treatment " item,
Standard curve is prepared, and prepares blank sample simultaneously, records chromatogram；Using testing concentration as abscissa, determinand and internal standard
Peak area ratio be ordinate, carries out regressing calculation with weighting (W=1/x2) least square method, drafting standard curve；
Preci-sion and accuracy is tested：
The basic, normal, high Quality Control working solution of hybrid standard is taken, adds blank whole blood and urine, is vortexed and mixes, be made into containing determinand
Concentration is respectively 0.05,1,20 μ g/mL drug containing whole blood and urine；Every batch of each concentration prepares 5 parts, does 3 batches altogether；By " sample
Operated under processing " item；Its measured concentration is calculated according to every batch of equation of linear regression, calculate each concentration the degree of accuracy, batch in and
Betweenrun precision, precision are represented with relative standard deviation (RSD)；
Recovery test：
It is respectively 0.05,1,20 μ g/ to take basic, normal, high concentration hybrid standard Quality Control working solution to be configured to containing testing concentration
Each 5 parts of mL drug containing whole blood and urine, by being operated under " sample preparation " item, record sample and internal standard peak area AS1, AS2 and
AIS1；(taking a collection of precision data to calculate) separately presses operation gained bare substrate under " sample preparation " item with blank whole blood or urine
Liquid, hybrid standard working solution is added, prepare the contrast solution of 3 same concentrations, each concentration is parallel to prepare 3 parts, records sample
And internal standard peak area and average AS3, AS4 and AIS2 are calculated, with AS1/AS3 × 100%, AS2/AS4 × 100% and AIS1/
AIS2 × 100% calculates the rate of recovery.
As a result show, the pretreatment process of the inventive method sample is easy, quick, and needs sample size few, and what is used is organic
Solvent load is few；Using HP-5MS capillarys gas chromatographic column and mass detector, 4 kinds of amphetamines in blood and urine are determined
Class, ketamine, pethidine, the content of methadone, detection is easy, quick, and high sensitivity, the degree of accuracy are good, can significantly increase poison
Judge fixed efficiency.
Table 2 is batch interior and betweenrun precision, the degree of accuracy and extraction recovery the data of determinand in people's whole blood.
Table 3 is batch interior and betweenrun precision, the degree of accuracy and extraction recovery the data of determinand in human urine.
Table 2
Table 3
Claims (5)
1. determine the method for amphetamine in blood and urine, ketamine, pethidine and methadone, it is characterised in that will extract
Liquid is directly measured using gas chromatography-mass spectrometry, is comprised the steps：
(1) blood or urine sample are pre-processed
Blood or urine sample are taken, adds internal standard MAMP-D5 0.2-1 μ g, 10%NaOH solution is added and is adjusted to the sample by force
Alkalescence, Extraction solvent is added, vortex mixed 2min, 10000rpm centrifugation 5min, shifts upper organic phase；
(2) using 4 kinds of amphetamines, ketamine, pethidines in gas chromatography/mass spectrometry blood or urine sample
With the concentration of methadone；The condition of the chromatogram is：
Chromatographic column：HP-5MS capillary columns, 30m × 0.25mm × 0.25 μm；Column temperature：100℃1.5min—25℃/min—280
℃15min；The solvent delay time：3min；Injection port/transmission line temperature：250℃/280℃；Carrier gas：High-purity He, constant current 1mL/
min；EI sources electron energy：70Ev；Scan mode：Salbutamol Selected Ion Monitoring SIM.
2. the method as described in claim 1, it is characterised in that described amphetamine compound is amphetamine, methylbenzene third
Amine, methylene dioxamphetamine and/or/methylene benzylene chloride propylamine.
3. the method as described in claim 1, it is characterised in that the Extraction solvent is 1-chlorobutane.
4. the method as described in claim 1, it is characterised in that be not related to extraction in described blood and urine sample pretreatment
Liquid volatilizes process, and extract solution direct injected gas chromatograph-mass spectrometer (GC-MS) is detected.
5. the method as described in claim 1, it is characterised in that described blood or urine sample sample is 0.2-1mL.
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| CN106501414A (en) * | 2016-12-07 | 2017-03-15 | 公安部物证鉴定中心 | A kind of method that homogenizes of amphetamine tablet |
| CN106645487B (en) * | 2016-12-28 | 2019-12-17 | 上海微谱化工技术服务有限公司 | Detection and analysis method of methamphetamine in weight-reducing drug |
| CN107340347B (en) * | 2017-05-08 | 2019-11-19 | 公安部物证鉴定中心 | The method for preparing purified of Sauteralgyl standard substance for forensic science illicit drugs inspection |
| CN109507354B (en) * | 2019-01-17 | 2021-02-02 | 浙江工业大学 | Method for determining content of K powder in human hair by flash evaporation-gas chromatography-mass spectrometry |
| CN110823855B (en) * | 2019-12-19 | 2023-06-06 | 鄂尔多斯应用技术学院 | Method for rapidly detecting amphetamine drugs in human urine |
| CN112649542B (en) * | 2021-01-14 | 2022-09-20 | 浙江海正药业股份有限公司 | Gas chromatography detection method for dicyclohexylamine in faviravir |
| CN115060815B (en) * | 2022-05-30 | 2023-06-16 | 广西大学 | Solid phase extraction-liquid chromatography-ion trap/time-of-flight mass spectrometry combined detection method for flumidone metabolites in human urine |
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