CN107478747A - The liquid chromatography mass screening method of unknown poisonous substance in blood - Google Patents

The liquid chromatography mass screening method of unknown poisonous substance in blood Download PDF

Info

Publication number
CN107478747A
CN107478747A CN201710700674.6A CN201710700674A CN107478747A CN 107478747 A CN107478747 A CN 107478747A CN 201710700674 A CN201710700674 A CN 201710700674A CN 107478747 A CN107478747 A CN 107478747A
Authority
CN
China
Prior art keywords
mobile phase
target detection
blood
drugs
formic acid
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.)
Granted
Application number
CN201710700674.6A
Other languages
Chinese (zh)
Other versions
CN107478747B (en
Inventor
赵培铎
宋丽娟
张广华
高宏
高中勇
杨崇俊
郭杰
李鹏
张兆宏
吕惊晗
张春强
闫帅
夏侯秋锦
***
马江华
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Public Security Department Of Shandong Province
Original Assignee
Public Security Department Of Shandong Province
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Public Security Department Of Shandong Province filed Critical Public Security Department Of Shandong Province
Publication of CN107478747A publication Critical patent/CN107478747A/en
Application granted granted Critical
Publication of CN107478747B publication Critical patent/CN107478747B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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

Landscapes

  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)

Abstract

The invention discloses a kind of liquid chromatography mass screening method of unknown poisonous substance in blood：Blood sample to be detected is taken, adds acetonitrile precipitation albumen, is vibrated, centrifugation, supernatant is taken, 0.22 μm of organic membrane filtration of micropore, then carries out LC MS/MS analyses, judge whether contain toxins in blood sample to be detected according to analysis result；Instrument is selected from the XL 4000Q TRAP LC-MS instrument of AB companies ultraLC 100, or the QTRAP triplex tandem quadrupole mass spectrometers of 1100 liquid chromatogram AB of Agilent 3200.The present invention establishes the detection method of different classes of poisonous substance, detection is quick, accurate, give the detection limit of common poisons, ensure that the highly sensitive of all kinds of objects is effectively examined, the data supporting of science is provided for negative test result, then provides strong scientific basis for clinical diagnosis, rescue and the criminal investigation of correlation, lawsuit.

Description

The liquid chromatography-mass spectrography screening method of unknown poisonous substance in blood
Technical field
The present invention relates to the liquid chromatography-mass spectrography screening method of unknown poisonous substance in blood, belong to chemical substance detection technique Field.
Background technology
Common poisons examination occupies sizable proportion in forensic science physical and chemical inspection.Applicant is by investigating Shandong Case of being involved in drug traffic in the past 10 years is saved, finds problems be present in such case examination of material evidence：
(1) case-involving poison type showed increased, in some whether be poisoned in indefinite case, it is necessary to examination of investigating and prosecuting Poisonous substance is not limited solely to that certain is several or certain is a kind of, i.e., Objective is not strong.In such cases, it is several if still continuing to use out-of-date methods only The most common poisonous substance of kind carries out examination, it is most likely that causes missing inspection.
(2) at present, gas chromatography mass spectrometry method is the instrument analytical method that prefectures and cities of the whole province generally grasp and used, the method phase The sample-pretreating method answered is lack of standardization, is also examined or check without optimization.
(3) gas chromatography mass spectrometry method by instrument self performance by being limited, it is impossible to which some poisonous substances are carried out with highly sensitive effectively inspection Test.Though prefectures and cities introduce LC-MS equipment successively, fail the method exploitation of carry out system, it is impossible to make full use of liquid matter to join Poisonous substance detection sensitivity is improved with technology.
(4) though application of the LC-MS in poisonous substance examination appears in the newspapers, and pre-treatment step is excessively complicated, and all points Analysis thing is analyzed under unified liquid-phase condition, and effect is unsatisfactory.Simultaneously as instrument brand, model difference, related Conditions and data can not be directly as this province forensic science poisonous substance examination foundation.
(5) systematicness examination is carried out to the detection limit of case-involving poisonous substance using LC-MS technology and still belongs to blank, negative findings Evaluate the data supporting of shortage science.
In view of the above circumstances, to meet the needs of public security work under the new situation, it is necessary to provide it is a kind of it is with versatility, Screening method easy to operate.
The content of the invention
For above-mentioned prior art, the invention provides a kind of liquid chromatography-mass spectrography examination side of unknown poisonous substance in blood Method.The application system has carried out agricultural chemicals (including organic phosphates, carbamates, chrysanthemum esters, organochlorine class), herbicide (bag Include amide-type, heterocyclic oxy group phenoxy group fatty acid), hypnotic sedative activity (including the miscellaneous nitrogen Zhuo class of benzo, phenothiazines, barbital Other common hypnotic and sedatives such as class and zopiclone), the inspection of raticide, amphetamine, the poisonous substance such as m orphine and other drugs Proved recipe jurisprudential study, their detection limit is obtained in optimal conditions, provide data supporting for negative findings evaluation, be then phase Clinical diagnosis, rescue and criminal investigation, the lawsuit of pass provide strong scientific basis.
The present invention is achieved by the following technical solutions：
The liquid chromatography-mass spectrography screening method of unknown poisonous substance in a kind of blood：Blood sample 1.0mL to be detected is taken, is added 2.0mL acetonitrile precipitation albumen, 10min is vibrated, centrifuge (12000r/min, 5min), take supernatant, 0.22 μm of organic filter membrane of micropore Filtering, LC-MS/MS analyses are then carried out, judge whether contain toxins in blood sample to be detected according to analysis result；Institute AB companies ultraLC 100-XL-4000Q TRAP LC-MS instrument, or the liquid chromatogram-AB of Agilent 1100 are selected from instrument 3200QTRAP triplex tandem quadrupole mass spectrometers.
When using AB company's ultraLC 100-XL-4000Q TRAP LC-MS instrument, Mass Spectrometry Conditions are：A) ion Source：Electron spray ionisation (ESI)；B) scan mode：Multiple-reaction monitoring pattern (MRM)；C) gas curtain gas (CUR)：20psi；D) collide Gas (CAD)：Medium；E) spray voltage (IS)：5500(-4500)V；F) temperature (TEM)：500℃；G) spraying gas (GS1)： 50psi；H) auxiliary heating gas (GS2)：50psi；I) interface heating (ihe)：on；J) collision cell entrance potential (EP)：10V；k) Collision cell exit potential (CXP)：6V；L) cluster voltage (DP) is removed, collision energy (CE) parameter sees attached list A.
Liquid-phase chromatographic analysis condition is as follows：
A) when target detection thing is organophosphor 1 and carbamates medicine：Chromatographic column：Waters BEH C18 1.7μ M2.1 × 50mm Column, flow velocity：0.3mL/min；Sample size：2 μ L, mobile phase A be 0.1% formic acid (mass percent), 5mM ammonium acetate solutions, Mobile phase B are methanol；Eluent gradient elution program is shown in Table 1.
Table 1：Eluent gradient elution program
B) when target detection thing is organophosphor 2：Chromatographic column：1.7 μm of 2.1 × 50mm Column of Waters BEH C18, Flow velocity：0.3mL/min；Sample size：2 μ L, mobile phase A are 5mM ammonium acetate solutions, and Mobile phase B is methanol；Eluent gradient is washed De- program is shown in Table 2.
Table 2：Eluent gradient elution program
C) when target detection thing is the miscellaneous nitrogen Zhuo class of benzo, phenothiazines and other cation analytical model medicines：Chromatographic column： 1.7 μm of 2.1 × 50mm Column of Waters BEH C18, flow velocity：0.3mL/min；Sample size：2 μ L, mobile phase A are 0.1% formic acid, 5mM ammonium acetate solutions, Mobile phase B are methanol；Eluent gradient elution program is shown in Table 3.
Table 3：Eluent gradient elution program
D) when target detection thing is barbiturates and other anion analytical model medicines：Chromatographic column：Waters BEH 1.7 μm of 2.1 × 50mm Column of C18, flow velocity：0.3mL/min；Sample size：2 μ L, mobile phase A are water, and Mobile phase B is first Alcohol；Eluent gradient elution program is shown in Table 4.
Table 4：Eluent gradient elution program
E) when target detection thing is raticide：Chromatographic column：1.7 μm of 2.1 × 50mm Column of Waters BEH C18, stream Speed：0.3mL/min；Sample size：2 μ L, mobile phase A are 0.1% aqueous formic acid, and Mobile phase B is methanol；Eluent gradient elutes Program is shown in Table 5.
Table 5：Eluent gradient elution program
F) when target detection thing is quaternary ammonium salt：Chromatographic column：2.7 μm of 2.1 × 50mm Column of HILIC, flow velocity： 1.0mL/min；Sample size：5 μ L, mobile phase A are 0.1% formic acid, 5mM ammonium acetate solutions, and Mobile phase B is acetonitrile；Mobile phase Gradient elution program is shown in Table 6.
Table 6：Eluent gradient elution program
G) when target detection thing is drugs class：Chromatographic column：1.7 μm of 2.1 × 50mm Column of Waters BEH C18, Flow velocity：0.3mL/min；Sample size：2 μ L, mobile phase A are 0.1% aqueous formic acid, and Mobile phase B is acetonitrile；Eluent gradient is washed De- program is shown in Table 7.
Table 7：Eluent gradient elution program
When using 1100 liquid chromatogram-AB 3200QTRAP triplex tandem quadrupole mass spectrometers of Agilent, mass spectrum bar Part is：A) spray voltage (IS):5500V/-4500V；B) gas curtain gas (CUR):25psi；C) atomization gas (GS1):65psi；d) Auxiliary heating gas (GS2):55psi；E) temperature degree (TEM) is aided in:650℃；F) ion residence time：70ms；G) scan pattern： MRM；H) retention time of malicious (medicine) thing sees attached list B with fragments characteristic ion.
Liquid phase chromatogram condition is as follows：Chromatographic column：Eclipse XDB-C18(4.6mm×150mm,5μm)；Sample size：10μ L；
Liquid chromatogram elution requirement：
A) target detection thing be the miscellaneous nitrogen Zhuo class of benzo, phenothiazines, carbamates, organic phosphates 1 and it is other just from During sub- analytical model medicine：Mobile phase：A：Methanol；B：5mM NH4The AC aqueous solution；C：0.1% aqueous formic acid；Eluent gradient Setting is shown in Table 8.
The eluent gradient of table 8 is set
B) when target detection thing is organic phosphates 2：Mobile phase：A：Methanol；B：5mM NH4The AC aqueous solution；Eluent gradient Setting is shown in Table 9.
The eluent gradient of table 9 is set
C) when target detection thing is barbiturates and other anion analytical model medicines：Mobile phase：A：Methanol；B：Water； Eluent gradient sets and is shown in Table 9.
D) when target detection thing is raticide class：Mobile phase：A：Methanol；B：0.1% aqueous formic acid；Eluent gradient is set It is shown in Table 9.
E) when target detection thing is drugs 1：Analysis condition is same a) shown in item.
F) when target detection thing is drugs 2：Mobile phase：A：Acetonitrile；B：5mM NH4The AC aqueous solution；C：0.1% formic acid is water-soluble Liquid；Eluent gradient sets and is shown in Table 8.
G) when target detection thing is drugs 3：Mobile phase：A：Acetonitrile；B：0.1% aqueous formic acid；Eluent gradient is set It is shown in Table 9.
Target detection thing referred to above is classified as follows：
(1) organophosphor 1 (13 kinds)：Methidathion, Azodrin, flolimat, parathion-methyl, orthene, chlopyrifos, Phosalone, sulfotep, malathion, Isofenphos methyl, DDVP, acephatemet, Rogor.
(2) organophosphor 2 (4 kinds)：Thimet, parathion, Terbufos, phoxim.
(3) carbamates medicine (8 kinds)：Aphox, carbofuran, Methomyl, MTMC, Mobucin, Aldicarb, tears Wire of going out sulfone, Aldicarb sulfone.
(4) the miscellaneous nitrogen Zhuo class medicine of benzo (12 kinds)：Stable, alprazolam, Lorazepam, estazolam, triazolam, chlorine nitrogen Flat, librium, carbamazepine, midazolam maleate, Oxazepam, clonazepam, 7- amino clonazepams.
(5) barbiturate (5 kinds)：Barbital, phenobarbital, amytal, allyl isopropyl barbital, speed can Sleep.
(6) phenothiazines (5 kinds)：Chlorpromazine, promethazine hydrochloride, imipramine, triperazine, perphenazine.
(7) quaternary ammonium salt medicine (a kind)：Paraquat.
(8) raticide (2 kinds)：Bromadiolone, Brodifacoum.
(9) drugs (22 kinds)：
Drugs 1：Cannabidiol, THC；
Drugs 2：Methcathinone, ***e, morphine and codeine and their derivative；
Drugs 3：Cathinone, common amphetamine and other drugs；
(10) other drugs：
a：Cation analytical model medicine (17 kinds)：Aminopyrine, zopiclone, doxepin, amitriptyline, miltown, Pethidine hydrochloride, antipyrine, caffeine, chlorpheniramine, Tai Erdeng, prednisone acetate, fentanyl citrate, Triamcinolone acetonide, salt Sour diphenoxylate, brufen, Halcinonide, SKF525。
b：Anion analytical model medicine (2 kinds)：Phenytoinum naticum, analgin.
Further, with the target detection thing from the addition detection limit concentration to blank blood sample or internal standard compound (cation of Pattern internal standard compound is SKF525A, negative ion mode internal standard compound is allyl isopropyl barbital) and negative control is used as, with to blank blood 2~5 times of amount target detection things of detection limit concentration are added in liquid sample as positive control；Evaluated according to testing result：
Under identical experiment condition, the chromatographic peak retention time and the addition target detection that occur in blood sample to be detected The chromatographic peak retention time of the control sample of thing compares, and relative deviation is in ± 5%, and fragments characteristic ion occurs, institute The ion relative abundance of selection than with add reference substance ion relative abundance than relative error be no more than model as defined in table 10 Enclose, then can determine whether this compound in sample be present.
The maximum allowable relative error (%) of the relative ion abundance ratio of table 10
Positive findings is evaluated：If Appendix B/appendix C toxicity composition is detected in blood sample to be detected, and blank blood Sample is noiseless, then positive findings is reliable；If detect toxins in blood sample to be detected and blank blood sample is also in The positive, then positive findings is unreliable.
Negative findings is evaluated：Respective objects thing or internal standard compound are detected in blank addition sample, and in blood sample to be detected Related poisonous substance is not detected, then negative findings is reliable；It is cloudy if not detecting respective objects thing or internal standard compound in blank addition sample Property result is unreliable.
The liquid chromatography-mass spectrography screening method of unknown poisonous substance, establishes the inspection of different classes of poisonous substance in the blood of the present invention Survey method, detection is quick, accurate, optimizes liquid phase chromatogram condition, Mass Spectrometry Conditions, gives common poisons and (cover method substantially The common poisons that front yard scientific domain is related to) detection limit (seeing attached list C), it is ensured that all kinds of objects it is highly sensitive effectively examine, be Negative test result provides the data supporting of science, is then provided for clinical diagnosis, rescue and the criminal investigation of correlation, lawsuit Strong scientific basis.In project research process, project team constantly summarizes each stage achievement in research, and in time with reality Border, which is handled a case, to be combined, and is run reason case more than 100 jointly and is risen, obtains accurate, reliable qualification result, played project achievement in research Act under battle conditions.
Brief description of the drawings
Fig. 1：The miscellaneous nitrogen Zhuo class of benzo and phenothiazines (methanol) spectrogram.Fig. 2：The miscellaneous nitrogen Zhuo class of benzo and phenothiazines medicine Thing (acetonitrile) spectrogram.Fig. 3：Organophosphor 1 (methanol) spectrogram.Fig. 4：Organophosphor 1 (acetonitrile) spectrogram.Fig. 5：Raticide (methanol) spectrogram. Fig. 6：Raticide (acetonitrile) spectrogram.Fig. 7：Drugs (acetonitrile) spectrogram.Fig. 8：Drugs (methanol) spectrogram.Fig. 9：Organophosphor 1 and amino first Esters of gallic acid medicine (5mM NH4The aqueous formic acid of the AC aqueous solution -0.1%) spectrogram.Figure 10：Organophosphor 1 and carbamates medicine Thing (0.1% formic acid) spectrogram.Figure 11：Organophosphor 1 and carbamates medicine (5mM NH4AC) spectrogram.Figure 12：Organophosphor 2 (5mM NH4AC) spectrogram.Figure 13：(the 5mM NH of organophosphor 24The aqueous formic acid of the AC aqueous solution -0.1%) spectrogram.Figure 14：Organophosphor 2 (0.1% formic acid) spectrogram.Figure 15：Barbiturate (pure water) spectrogram.Figure 16：Barbiturate (0.1% formic acid) spectrogram. Figure 17：Barbiturate (5mM NH4AC) spectrogram.
Embodiment
With reference to embodiment, the present invention is further illustrated.
Involved instrument, reagent, material etc. in following embodiments, it is existing in the prior art unless otherwise noted Conventional instrument, reagent, material etc., can be obtained by regular commercial sources.Involved experimental method in following embodiments, inspection Survey method etc., it is existing normal experiment method, detection method etc. in the prior art unless otherwise noted.
Test 1 liquid phase chromatogram condition optimization (AB Sciex ultraLC 100-XL-4000Q TRAP LC-MS systems Liquid-phase condition optimization)
Reservation, peak shape and sensitivity of the property of reagent selected by liquid chromatogram mobile phase to analyte have larger shadow Ring.In this research, we select common agents methanol or acetonitrile to examine or check analysis of organic phase constituent to inhomogeneity poisonous substance respectively Effect.On this basis, to the poisonous substance suitable for cation analytical model, respectively in 0.1% aqueous formic acid, 5mM NH4AC The aqueous solution or 5mM NH4Shadow of the water-phase component to analysis is examined or check under the conditions of the AC aqueous solution and 0.1% aqueous formic acid mix reagent Ring, to the poisonous substance suitable for anion analytical model, respectively in pure water, 5mM NH4The AC aqueous solution or 0.1% aqueous formic acid bar Influence of the water-phase component to analysis is examined or check under part.
(1) selection of organic phase：From experimental conditions as can be seen that the miscellaneous nitrogen Zhuo class of benzo and phenothiazines are with methanol Or acetonitrile as organic solvent when, can appearance, the peak width of most analytes uses acetonitrile within 0.1min When, miltown peak shape is bad, Oxazepam and clonazepam sensitivity extreme difference (referring to Fig. 1, Fig. 2).Organic phosphates, barbital Class, paraquat and other medicines are when by the use of methanol or acetonitrile as organic solvent, energy appearance, and peak width is in 0.1-0.2min Left and right (referring to Fig. 3~Fig. 4).Raticide class under the conditions of two kinds of organic phases can appearance, but utilize acetonitrile when being organic phase, mesh It is poor to mark thing peak shape, peak width is in 0.3min or so, and during with methanol, and peak shape and sensitivity have very big improvement, and peak width exists 0.15min or so (referring to Fig. 5, Fig. 6).To sum up, the peak shape and detection sensitivity of all kinds of all medicines are taken into account, being used as from methanol is had Machine phase reagent.
When drugs class medicine is by the use of methanol or acetonitrile as organic solvent, can appearance, but in peak shape methanol not as acetonitrile effect Fruit is good, and when using acetonitrile being organic phase, peak width is in 0.15min or so, and during with methanol, peak width (ginseng between 0.2-0.3min See Fig. 7, Fig. 8), therefore drugs class uses acetonitrile as organic phase.
(2) optimization of aqueous phase composition：Various medicines equal energy appearance under the conditions of different aqueous phases can be seen that by experiment, but The difference of peak shape and response be present, benzo miscellaneous nitrogen Zhuo, phenothiazines, organophosphor 1, carbamates poisonous substance and paraquat exist Under the conditions of three kinds of aqueous phases, peak width is within 0.1-0.2min, in contrast, uses 5mM NH4The AC aqueous solution and 0.1% During aqueous formic acid mix reagent, peak shape and response are better than other two kinds (referring to Fig. 9~Figure 11), therefore use 5mM NH4The AC aqueous solution and 0.1% aqueous formic acid mix reagent are as aqueous phase.Organophosphor 2 under the conditions of three kinds of aqueous phases, peak shape compared with Good, peak width is using 5mM NH between 0.1-0.2min4When the AC aqueous solution is as aqueous phase, 4 kinds of object response highests (referring to Figure 12~Figure 14), so from 5mM NH4The AC aqueous solution is as aqueous phase reagent.Barbiturates and suitable for anion point Peak width is between 0.1-0.2min in three kinds of aqueous phases for the other medicines of analysis pattern, during using pure water, response highest (referring to Figure 15~Figure 17)；And drugs and raticide are best using 0.1% aqueous formic acid analytical effect.
Test the liquid-phase condition optimization of 2Agilent 1100-AB Sciex 3200QTRAP LC-MS systems
(1) selection of organic phase
From experimental conditions as can be seen that the miscellaneous nitrogen Zhuo class medicine of benzo is when by the use of methanol or acetonitrile as organic solvent, equal energy Appearance, and signal intensity no significant difference.Under than relatively low flow conditions, the peak width of most analytes is in 0.5- Between 0.75min, but during use acetonitrile, Clozapine spectral peak broadening to 3min or so.Different organic solvents are to phenothiazines medicine The influence of thing analysis clearly, such analyte not appearance during using acetonitrile, and can obtain good detection during with methanol. Barbiturate and carbamate chemicals for agriculture are when by the use of methanol or acetonitrile as organic solvent, energy appearance, and peak width is equal In 0.5min or so.By contrast, signal strength differences of the Aphox with Aldicarb under two kinds of reagent conditions are little, and other Detection sensitivity of several analytes under the conditions of methanol is substantially better than acetonitrile.When being analyzed with methanol organic phosphates, mesh Mark thing can obtain good detection, and during with acetonitrile, parathion-methyl in 20min do not mix by appearance, metrifonate, DDVP, first Phosphorus, parathion, Terbufos response are very low, and the signal intensity of other several analytes is also markedly less than methanol.Raticide class is at two kinds Under the conditions of organic phase can appearance, but utilize acetonitrile object peak shape extreme difference, sensitivity be low, and uses methanol when being organic phase When, peak shape and sensitivity have very big improvement.Analysis to other Common drugs, if being used as organic phase, amitriptyline by the use of acetonitrile Appearance, caffeine do not trail seriously with doxepin, peak shape extreme difference.Aminopyrine, zopiclone, pethidine hydrochloride, caffeine, peace Though it can be detected for materials more several than woods etc., it is much lower during signal intensity ratio methanol.In drugs class material, except cannabidiol Signal intensity is substantially better than outside acetonitrile under the conditions of methanol with THC, and other analytes are had more under the conditions of acetonitrile High detection sensitivity.To sum up, the peak shape and detection sensitivity of all kinds of cytotoxic drugs are taken into account, common poisons class is used as from methanol to be had Machine phase reagent；In drugs in addition to cannabidiol and THC select methanol, other analytes are organic phase from acetonitrile.
(2) optimization of aqueous phase composition
Pass through experiment, it has been found that the cannabidiol and tetrahydrochysene suitable for the common poisons and drugs of positive ion mode are big Numb phenol, during by the use of 0.1% aqueous formic acid as aqueous phase, signal intensity substantially reduces, but partial target thing peak shape makes moderate progress, Consider detection sensitivity and peak shape, we are emphatically to 5mM NH4AC and 5mM NH4The aqueous formic acid of the AC aqueous solution -0.1% The analysis situation of mix reagent compares；Other drugs in addition to cannabidiol and THC, use 5mM NH4AC For aqueous phase when, even there is broadening and formed to 4min or so in generally existing conditions of streaking, cannabinol spectral peak corresponding with methadone For situation about wrapping greatly, and the detection sensitivity of analyte is not high.In consideration of it, we focus on to 0.1% formic acid to these drugs The aqueous solution and 5mM NH4The analysis situation of the aqueous formic acid mix reagent of the AC aqueous solution -0.1% is compared.
The miscellaneous nitrogen Zhuo class 5mM NH of benzo4When AC is as aqueous phase, alprazolam, Lorazepam, estazolam, triazolam, Clozapine, librium, carbamazepine, midazolam peak shape are bad, and with 5mM NH4AC-0.1% formic acid mix reagent conducts During aqueous phase, all analytes can not only obtain good peak shape, and the signal response of most objects has substantially Enhancing.
Phenothiazines 5mM NH4When AC is as aqueous phase, object peak trails and most of chromatographic peak has bifurcated tendency, Peak width is between 0.75min-1min.With 5mM NH4When AC-0.1% formic acid mix reagent is as aqueous phase, all analyte peak shapes Well, peak width is in 0.25min or so.In addition to triperazine, the signal response of other analytes is remarkably reinforced.
Carbamates 5mM NH4When AC is as aqueous phase, there is bifurcated tendency at object peak, and peak width is in 0.4min- Between 0.6min.With 5mM NH4When AC-0.1% formic acid mix reagent is as aqueous phase, the peak width of all analytes narrows, and Peak shape is improved.Wherein, signal response difference of the Methomyl with Aldicarb under two kinds of reagent conditions is little, other analytes When with mixing water phase reagent, sensitivity improves.
Organic phosphates 5mM NH4When AC-0.1% formic acid mix reagent is as aqueous phase, object peak shape is improved, but Be thimet, parathion, phoxim, four kinds of analytes of Terbufos using mix reagent when, signal intensity decline it is more apparent.
Other medicines 5mM NH4When AC is as aqueous phase, doxepin, amitriptyline, pethidine hydrochloride hangover are serious, peak width Between 0.8min to 1min.During by the use of mix reagent as aqueous phase, peak shape is greatly improved, response signal enhancing.
When barbiturates is by the use of pure water as aqueous phase, signal is most strong, uses 5mM NH instead4AC or during 0.1% formic acid, signal has Different degrees of reduction.
Raticide class：Under the conditions of three kinds of aqueous phases, pure water signal is most strong, and 0.1% formic acid takes second place, 5mM NH4AC is worst.But make During with pure water, Bromadiolone appearance is bimodal, and Brodifacoum spectral peak substantially divides.
Cannabidiol and THC 5mM NH4AC or 5mM NH4AC-0.1% formic acid mix reagents are as aqueous phase When, peak shape is preferable, and sensitivity is close.
In other drugs, amphetamine, crystal methamphetamine, MDA, Cathinone, methadone are better than with 0.1% aqueous formic acid 5mM NH4AC-0.1% formic acid mix reagents；Methcathinone, morphine, Norcodeine, normorphine, ***e 5mM NH4AC-0.1% formic acid mix reagent effects are more preferable；MDMA, MDEA, 6- acetylmorphine, codeine, 6- codeines, hemp Phenol, ephedrine, methylephedrine, the ketamine effect under the conditions of two kinds of aqueous phases are close.
Consider various kinds of drug analysis situation, the miscellaneous nitrogen Zhuo class of benzo, phenothiazines, carbamate in common poisons Class, organic phosphates 1 (methidathion, Azodrin, flolimat, parathion-methyl, orthene, sulfotep, malathion, first Base isofenphos, DDVP, acephatemet, Rogor) and suitable for other common poisons of positive ion mode select 5mM NH4AC- The mix reagent of 0.1% formic acid is as aqueous phase；Thimet, parathion, phoxim and Terbufos are because of signal in acid condition It is obvious to reduce, so from 5mM NH4AC is as aqueous phase；Barbiturates and the other medicines choosing suitable for anion analytical model Use pure water；Raticide class is from 0.1% formic acid as aqueous phase.In common drugs, cannabidiol, THC, ***e, first card Western ketone, morphine and codeine and their derivative select 5mM NH4The mix reagent of AC-0.1% formic acid is as aqueous phase；Cassie Ketone, amphetamine and other drugs are from 0.1% aqueous formic acid as aqueous phase.
Test the influence of 3 flow rate of mobile phase
We choose carbamates and examine influence of the flow velocity to analysis with raticide class respectively.When flow velocity is 0.7mL/ During min, most of carbamates analyte spectral peaks have a bifurcation, and raticide class spectral peak is wider；Flow velocity is promoted to After 1.0mL/min, analyte retention time is shortened, and peak shape is improved.In testing below, flow rate of mobile phase is disposed as 1.0mL/min。
Test 4 matrix interferences
Precision draws 12 parts of blank whole bloods and each 1mL of blank water, is divided into 3 groups.Every group is added standard substance, concentration point respectively Not Wei 20,50,100ng/mL, by 1.5 whole blood sample processing item methods handle determine, from experimental result as can be seen that each medicine It is close with the signal intensity in water in blood, it was demonstrated that directly to can be very good to remove the base in blood with acetonitrile precipitation albumen Matter is disturbed, and this sample-pretreating method is simple and effective.Specific data are shown in Table 11.
The blood matrix of the barbiturate of table 11 influences examination
Test 5 method stability tests
Precision draws 12 parts of each 1mL of blank whole blood, adds standard substance solution amytal (20ng/mL), department respectively Can barbital (20ng/mL), stable (1ng/mL), chlorpromazine (5ng/mL), Bromadiolone (1ng/mL), flolimat (2ng/ ML), carbofuran (1ng/mL), Azodrin (1ng/mL), phoxim (20ng/mL), Terbufos (20ng/mL), phenytoinum naticum (20ng/mL), chlorpheniramine (2ng/mL), fentanyl (20ng/mL), cannabinol (20ng/mL), ephedrine (20ng/mL), chloramines Ketone (20ng/mL), handle and determine by whole blood sample processing item method, relative standard deviation is 2.8%-9.8% (n=12), is seen Table 12, table 14.
The stability of the barbiturate of table 12
Case one：On December 18th, 2015,19 days, Zibo high and new technology industrial development zone Liu Zhi by force with girl friend Sun Qi plums successively occur stomachache, The symptoms such as hematuria, and gradually aggravate, examination in hospital shows coagulation disorders.To find out cause of disease symptomatic treatment, December 28, carry Soy cruet censorship in Liu Zhiqiang, Sun Qi plum venous blood and the strong families of Liu Zhi is taken, is analyzed through LC-MS instrument, detects raticide Bromadiolone Composition, patient are given treatment in time.Conclusion accordingly, further investigate thoroughly that suspect Chen Lin because discontented Liu Zhiqiang is said good-bye therewith, is stolen Liu Zhiqiang dwelling being slipped into steathily the crime fact that Bromadiolone causes it to be poisoned being launched in soy cruet, this plays revenge and poisoned case water falling rocks Go out.
Case two：When on June 17th, 2016, a shop Zhu Hui and male's client meetings, the drink of client offer is drunk Gone into a coma after material.Next day is suspected by fan traitor, after reporting a case to the security authorities, extracts Zhu Hui blood sample, though by the catabolism of tens hours, liquid matter connection Hypnotic sedative class medicine clonazepam, aminopyrine composition are still therefrom detected with instrument.
Case three：On July 1st, 2016, the new alarm of the neat member of the high valley villager in Yiyuan County Shandong villages and small towns claim：He is from June, 2016 Start saliva morning on the 26th, discovery has blood in the mouth, and leg also aches, and symptom is increasingly severe within several afterwards days, on the face, in nose, tooth Oulorrhagia；It is blue on leg, swollen；It dare not walk, pin aches once the leg that lands.On June 30th, 2016 goes to Yiyuan County hospital to be examined Look into, doctor does not give definite diagnosis to its illness, only suspects that poisoning causes.After my physics and chemistry room accepts this case, set about aliging immediately Member is newly eaten used soy sauce, vinegar, barreled peanut oil, white wine, salt, white sugar, little cake and the new blood of neat member and tested, neat from sending Raticide Brodifacoum composition is detected in first new blood.
Case four：On August 16th, 2016, the neat new wife Liu Tonglan alarms of member claim：She went to Linzhou City on June 8th, 2016 There is that the leg back of the body is blue, bleeding in the mouth the day before yesterday of daughter man of area, after going to Linzhou City to build hospital admission, when one section of traumatism treatment Time recovers normal.And occur bleeding in the mouth second day since after on July 23rd, 2016 family for returning to Yiyuan Lu Cun, have a pain in the leg Deng similar symptom, there is no clear and definite diagnostic result after going to Yiyuan County Yiyuan medical.After the merit is learnt in my physics and chemistry room, it is desirable to the Yihe River If the edible sample that source county telephone central office policeman in charge of the case Liu contacts after being gone home for 16th with blue August all extracts censorship, and from given metal Vegetable oil in bucket and detection raticide Brodifacoum composition in Liu Tonglan blood, it is the key evidence of qualitative offer of case.
Subordinate list A
Instrument (AB ultraLC 100-XL-4000Q TRAP) is to 89 kinds of poison (medicine) things and the analytical parameters of 2 kinds of internal standard compounds
Subordinate list B
Analysis of the instrument (Agilent 1100-AB Sciex 3200Q TRAP) to 84 kinds of poison (medicine) things and a kind of internal standard compound Parameter
Detection limit of the subordinate list C medicines on AB Sciex ultraLC 100-XL-4000QTRAP

Claims (8)

  1. A kind of 1. liquid chromatography-mass spectrography screening method of unknown poisonous substance in blood, it is characterised in that：Blood sample to be detected is taken, Acetonitrile precipitation albumen is added, is vibrated, centrifugation, supernatant is taken, 0.22 μm of organic membrane filtration of micropore, then carries out LC-MS/MS points Analysis, judges whether contain toxins in blood sample to be detected according to analysis result；Instrument is selected from AB companies ultraLC 100-XL-4000Q TRAP LC-MS instrument, or the liquid chromatogram-AB 3200QTRAP triplex tandem quadrupole rods of Agilent 1100 Mass spectrograph；
    When using AB company's ultraLC 100-XL-4000Q TRAP LC-MS instrument, Mass Spectrometry Conditions are：A) ion gun：Electricity Spraying ionization；B) scan mode：Multiple-reaction monitoring pattern；C) gas curtain gas：20psi；D) collision gas：Medium；E) spray voltage： 5500/-4500V；F) temperature：500℃；G) spraying gas：50psi；H) auxiliary heating gas：50psi；I) interface heats：on；J) touch Hit chamber inlet voltage：10V；K) collision cell exit potential：6V；L) cluster voltage is removed；
    Liquid-phase chromatographic analysis condition is as follows：
    A) when target detection thing is organophosphor 1 and carbamates medicine：Chromatographic column：Waters BEH C18 1.7μm2.1 × 50mm Column, flow velocity：0.3mL/min；Sample size：2 μ L, mobile phase A are 0.1% formic acid, 5mM ammonium acetate solutions, are flowed Dynamic phase B is methanol；
    B) when target detection thing is organophosphor 2：Chromatographic column：1.7 μm of 2.1 × 50mm Column of Waters BEH C18, stream Speed：0.3mL/min；Sample size：2 μ L, mobile phase A are 5mM ammonium acetate solutions, and Mobile phase B is methanol；
    C) when target detection thing is the miscellaneous nitrogen Zhuo class of benzo, phenothiazines and other cation analytical model medicines：Chromatographic column： 1.7 μm of 2.1 × 50mm Column of Waters BEH C18, flow velocity：0.3mL/min；Sample size：2 μ L, mobile phase A are 0.1% formic acid, 5mM ammonium acetate solutions, Mobile phase B are methanol；
    D) when target detection thing is barbiturates and other anion analytical model medicines：Chromatographic column：Waters BEH C18 1.7 μm of 2.1 × 50mm Column, flow velocity：0.3mL/min；Sample size：2 μ L, mobile phase A are water, and Mobile phase B is methanol；
    E) when target detection thing is raticide：Chromatographic column：1.7 μm of 2.1 × 50mm Column of Waters BEH C18, flow velocity： 0.3mL/min；Sample size：2 μ L, mobile phase A are 0.1% aqueous formic acid, and Mobile phase B is methanol；
    F) when target detection thing is quaternary ammonium salt：Chromatographic column：2.7 μm of 2.1 × 50mm Column of HILIC, flow velocity：1.0mL/ min；Sample size：5 μ L, mobile phase A are 0.1% formic acid, 5mM ammonium acetate solutions, and Mobile phase B is acetonitrile；
    G) when target detection thing is drugs class：Chromatographic column：1.7 μm of 2.1 × 50mm Column of Waters BEH C18, flow velocity： 0.3mL/min；Sample size：2 μ L, mobile phase A are 0.1% aqueous formic acid, and Mobile phase B is acetonitrile；
    When using 1100 liquid chromatogram-AB 3200QTRAP triplex tandem quadrupole mass spectrometers of Agilent, Mass Spectrometry Conditions are： A) spray voltage:5500V/-4500V；B) gas curtain gas:25psi；C) atomization gas:65psi；D) auxiliary heating gas:55psi；e) Aid in temperature degree:650℃；F) ion residence time：70ms；G) scan pattern：MRM；
    Liquid phase chromatogram condition is as follows：Chromatographic column：Eclipse XDB-C18(4.6mm×150mm,5μm)；
    Liquid chromatogram elution requirement：
    A) target detection thing is the miscellaneous nitrogen Zhuo class of benzo, phenothiazines, carbamates, organic phosphates 1 and other cations point When analysing model drug：Mobile phase：A：Methanol；B：5mM NH4The AC aqueous solution；C：0.1% aqueous formic acid；
    B) when target detection thing is organic phosphates 2：Mobile phase：A：Methanol；B：5mM NH4The AC aqueous solution；
    C) when target detection thing is barbiturates and other anion analytical model medicines：Mobile phase：A：Methanol；B：Water；
    D) when target detection thing is raticide class：Mobile phase：A：Methanol；B：0.1% aqueous formic acid；
    E) when target detection thing is drugs 1：Analysis condition is same a) shown in item；
    F) when target detection thing is drugs 2：Mobile phase：A：Acetonitrile；B：5mM NH4The AC aqueous solution；C：0.1% aqueous formic acid；
    G) when target detection thing is drugs 3：Mobile phase：A：Acetonitrile；B：0.1% aqueous formic acid；
    Target detection thing referred to above is classified as follows：
    (1) organophosphor 1：Methidathion, Azodrin, flolimat, parathion-methyl, orthene, chlopyrifos, Phosalone, Sulfotep, malathion, Isofenphos methyl, DDVP, acephatemet, Rogor；
    (2) organophosphor 2：Thimet, parathion, Terbufos, phoxim；
    (3) carbamates medicine：Aphox, carbofuran, Methomyl, MTMC, Mobucin, Aldicarb, Tinidazole glucose injection, Aldicarb sulfone；
    (4) the miscellaneous nitrogen Zhuo class medicine of benzo：Stable, alprazolam, Lorazepam, estazolam, triazolam, Clozapine, librium, Carbamazepine, midazolam maleate, Oxazepam, clonazepam, 7- amino clonazepams；
    (5) barbiturate：Barbital, phenobarbital, amytal, allyl isopropyl barbital, secobarbital sodium；
    (6) phenothiazines：Chlorpromazine, promethazine hydrochloride, imipramine, triperazine, perphenazine；
    (7) quaternary ammonium salt medicine：Paraquat；
    (8) raticide：Bromadiolone, Brodifacoum；
    (9) drugs：
    Drugs 1：Cannabidiol, THC；
    Drugs 2：Methcathinone, ***e, morphine and codeine and their derivative；
    Drugs 3：Cathinone, common amphetamine and other drugs；
    (10) other drugs：
    a：Cation analytical model medicine：Aminopyrine, zopiclone, doxepin, amitriptyline, miltown, pethidine hydrochloride, Antipyrine, caffeine, chlorpheniramine, Tai Erdeng, prednisone acetate, fentanyl citrate, Triamcinolone acetonide, diphenoxylate hydrochloride, Brufen, Halcinonide, SKF525；
    b：Anion analytical model medicine：Phenytoinum naticum, analgin.
  2. 2. the liquid chromatography-mass spectrography screening method of unknown poisonous substance in blood according to claim 1, it is characterised in that：With Into blank blood sample, the target detection thing of addition detection limit concentration or internal standard compound are as negative control, positive ion mode internal standard Thing is SKF525A, negative ion mode internal standard compound is allyl isopropyl barbital；It is dense to add detection limit into blank blood sample 2~5 times of amount target detection things of degree are as positive control；Evaluated according to testing result：
    Under identical experiment condition, the chromatographic peak retention time and the addition target detection thing that occur in blood sample to be detected The chromatographic peak retention time of control sample compares, and relative deviation is in ± 5%, and fragments characteristic ion occurs, selected Ion relative abundance than with add reference substance ion relative abundance than relative error be no more than scope as defined in table 10, then It can determine whether this compound in sample be present；
    The maximum allowable relative error (%) of the relative ion abundance ratio of table 10
  3. 3. the liquid chromatography-mass spectrography screening method of unknown poisonous substance in blood according to claim 1, it is characterised in that：When During using AB companies ultraLC 100-XL-4000Q TRAP LC-MS instrument, a)~g) in eluent gradient elution program according to It is secondary as shown in 1~table of table 7：
    Table 1：Eluent gradient elution program
    Table 2：Eluent gradient elution program
    Table 3：Eluent gradient elution program
    Table 4：Eluent gradient elution program
    Table 5：Eluent gradient elution program
    Table 6：Eluent gradient elution program
    Table 7：Eluent gradient elution program
  4. 4. the liquid chromatography-mass spectrography screening method of unknown poisonous substance in blood according to claim 1, it is characterised in that：When During using 1100 liquid chromatogram-AB of Agilent, 3200 QTRAP triplex tandem quadrupole mass spectrometers, a)~g) in mobile phase ladder Degree elution program is successively as shown in table 8, table 9, table 9, table 9, table 8, table 8, table 9：
    The eluent gradient of table 8 is set
    The eluent gradient of table 9 is set
  5. 5. the liquid chromatography-mass spectrography screening method of unknown poisonous substance in blood according to claim 1, it is characterised in that：When During using AB companies ultraLC 100-XL-4000Q TRAP LC-MS instrument, cluster voltage is removed, collision energy parameter sees attached list A.
  6. 6. the liquid chromatography-mass spectrography screening method of unknown poisonous substance in blood according to claim 1, it is characterised in that：When During using 1100 liquid chromatogram-AB of Agilent, 3200 QTRAP triplex tandem quadrupole mass spectrometers, the retention time of object B is seen attached list with fragments characteristic ion.
  7. 7. the liquid chromatography-mass spectrography screening method of unknown poisonous substance in blood according to claim 1, it is characterised in that：When During using AB companies ultraLC 100-XL-4000Q TRAP LC-MS instrument, the detection limit of object is referring to subordinate list C.
  8. 8. the liquid chromatography-mass spectrography screening method of unknown poisonous substance in blood according to claim 1, it is characterised in that：Take Blood sample 1.0mL to be detected, 2.0mL acetonitrile precipitation albumen is added, vibrate 10min, centrifugation, 12000r/min, 5min, take Clear liquid, 0.22 μm of organic membrane filtration of micropore, LC-MS/MS analyses are then carried out, blood sample to be detected is judged according to analysis result Whether contain Toxic in product.
CN201710700674.6A 2017-05-10 2017-08-16 The liquid chromatography-mass spectrography screening method of unknown poisonous substance in blood Active CN107478747B (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN2017103263816 2017-05-10
CN201710326381 2017-05-10

Publications (2)

Publication Number Publication Date
CN107478747A true CN107478747A (en) 2017-12-15
CN107478747B CN107478747B (en) 2019-11-08

Family

ID=60599644

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201710700674.6A Active CN107478747B (en) 2017-05-10 2017-08-16 The liquid chromatography-mass spectrography screening method of unknown poisonous substance in blood

Country Status (1)

Country Link
CN (1) CN107478747B (en)

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107991421A (en) * 2018-01-25 2018-05-04 北京和合医学诊断技术股份有限公司 The liquid phase chromatography analytical method of diazepam content in a kind of detection blood
CN107991420A (en) * 2018-01-25 2018-05-04 北京和合医学诊断技术股份有限公司 The liquid phase chromatography analytical method of carbamazepine content in a kind of detection blood
CN108037225A (en) * 2018-01-25 2018-05-15 北京和合医学诊断技术股份有限公司 The method that carbamazepine medicine content in on-line checking blood is pumped using double ternarys
CN108169362A (en) * 2017-12-19 2018-06-15 山东则正医药技术有限公司 It is a kind of to detach carbamazepine and method in relation to substance with liquid chromatography
CN108445099A (en) * 2018-03-12 2018-08-24 中国检验检疫科学研究院 The assay method of 12 kinds of local anesthetics in a kind of cosmetics
CN109085263A (en) * 2018-08-03 2018-12-25 杭州佰勤医疗器械有限公司 Liquid chromatography tandem mass spectrometry detects the kit of anti-schizophrenia drug and its application in serum plasma
CN109541107A (en) * 2018-11-30 2019-03-29 徐州佳生医药科技有限公司 A kind of method that LC-MS measures Carbamazepine in blood plasma
CN109828051A (en) * 2019-03-11 2019-05-31 芜湖市疾病预防控制中心 A kind of detection method of toxic compounds
CN110161167A (en) * 2019-06-28 2019-08-23 公安部禁毒情报技术中心 The storage and detection method of methcathinone in urine
CN110346470A (en) * 2019-07-04 2019-10-18 公安部物证鉴定中心 A kind of detection method of 3,4- methylene-dioxy methcathinone
CN110531014A (en) * 2019-03-11 2019-12-03 成都民用航空医学中心 The method that Liquid Chromatography-Tandem Mass Spectrometry detects 43 kinds of drugs in blood
CN112903849A (en) * 2021-01-21 2021-06-04 山东英盛生物技术有限公司 Method and kit for detecting eszopiclone content in blood and application of kit
CN113109491A (en) * 2020-01-13 2021-07-13 四川基因格司法鉴定中心 Universal method for detecting toxic drugs from biological samples
CN113406244A (en) * 2021-08-03 2021-09-17 四川大学 Common poison screening database and rapid screening method based on liquid chromatogram-rod orbit trap mass spectrum
CN114646711A (en) * 2020-12-21 2022-06-21 四川科瑞德制药股份有限公司 Detection method of impurities related to hydroxymethyl phenytoin

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102226794A (en) * 2011-03-28 2011-10-26 中华人民共和国连云港出入境检验检疫局 Liquid chromatography-tandom mass spectrometry detection method of thirty-one drugs in human blood
CN103808846A (en) * 2014-02-20 2014-05-21 福建国际旅行卫生保健中心 Series quadrupole-rod gas-chromatographic mass spectrometry detection method for 35 toxic medicaments in urine
CN103823008A (en) * 2014-03-14 2014-05-28 北京市疾病预防控制中心 Method for detecting unknown poison by establishing liquid chromatography-mass spectrometry database
WO2014150900A1 (en) * 2013-03-15 2014-09-25 Baylor Research Institute Methods and compositions for enhanced analyte detection from blood
CN107192788A (en) * 2017-05-10 2017-09-22 山东省公安厅 The gaschromatographic mass spectrometry screening method of unknown poisonous substance in blood

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102226794A (en) * 2011-03-28 2011-10-26 中华人民共和国连云港出入境检验检疫局 Liquid chromatography-tandom mass spectrometry detection method of thirty-one drugs in human blood
WO2014150900A1 (en) * 2013-03-15 2014-09-25 Baylor Research Institute Methods and compositions for enhanced analyte detection from blood
CN103808846A (en) * 2014-02-20 2014-05-21 福建国际旅行卫生保健中心 Series quadrupole-rod gas-chromatographic mass spectrometry detection method for 35 toxic medicaments in urine
CN103823008A (en) * 2014-03-14 2014-05-28 北京市疾病预防控制中心 Method for detecting unknown poison by establishing liquid chromatography-mass spectrometry database
CN107192788A (en) * 2017-05-10 2017-09-22 山东省公安厅 The gaschromatographic mass spectrometry screening method of unknown poisonous substance in blood

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
SEBASTIAN BROECKER等: "Development and practical application of a library of CID accurate mass spectra of more than 2,500 toxic compounds for systematic toxicological analysis by LC–QTOF-MS with data-dependent acquisition", 《ANAL BIOANAL CHEM》 *
姜凤丽等: "超高效液相色谱-串联四极杆飞行时间质谱法筛查人全血中150种药物与毒物", 《理化检验-化学分册》 *

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108169362A (en) * 2017-12-19 2018-06-15 山东则正医药技术有限公司 It is a kind of to detach carbamazepine and method in relation to substance with liquid chromatography
CN107991420A (en) * 2018-01-25 2018-05-04 北京和合医学诊断技术股份有限公司 The liquid phase chromatography analytical method of carbamazepine content in a kind of detection blood
CN108037225A (en) * 2018-01-25 2018-05-15 北京和合医学诊断技术股份有限公司 The method that carbamazepine medicine content in on-line checking blood is pumped using double ternarys
CN107991421A (en) * 2018-01-25 2018-05-04 北京和合医学诊断技术股份有限公司 The liquid phase chromatography analytical method of diazepam content in a kind of detection blood
CN108445099B (en) * 2018-03-12 2020-12-29 中国检验检疫科学研究院 Method for measuring 12 local anesthetics in cosmetics
CN108445099A (en) * 2018-03-12 2018-08-24 中国检验检疫科学研究院 The assay method of 12 kinds of local anesthetics in a kind of cosmetics
CN109085263A (en) * 2018-08-03 2018-12-25 杭州佰勤医疗器械有限公司 Liquid chromatography tandem mass spectrometry detects the kit of anti-schizophrenia drug and its application in serum plasma
CN109541107A (en) * 2018-11-30 2019-03-29 徐州佳生医药科技有限公司 A kind of method that LC-MS measures Carbamazepine in blood plasma
CN109828051A (en) * 2019-03-11 2019-05-31 芜湖市疾病预防控制中心 A kind of detection method of toxic compounds
CN109828051B (en) * 2019-03-11 2022-09-09 芜湖市疾病预防控制中心 Method for detecting toxic compound
CN110531014A (en) * 2019-03-11 2019-12-03 成都民用航空医学中心 The method that Liquid Chromatography-Tandem Mass Spectrometry detects 43 kinds of drugs in blood
CN110161167A (en) * 2019-06-28 2019-08-23 公安部禁毒情报技术中心 The storage and detection method of methcathinone in urine
CN110346470A (en) * 2019-07-04 2019-10-18 公安部物证鉴定中心 A kind of detection method of 3,4- methylene-dioxy methcathinone
CN113109491A (en) * 2020-01-13 2021-07-13 四川基因格司法鉴定中心 Universal method for detecting toxic drugs from biological samples
CN114646711A (en) * 2020-12-21 2022-06-21 四川科瑞德制药股份有限公司 Detection method of impurities related to hydroxymethyl phenytoin
CN112903849A (en) * 2021-01-21 2021-06-04 山东英盛生物技术有限公司 Method and kit for detecting eszopiclone content in blood and application of kit
CN112903849B (en) * 2021-01-21 2021-11-30 山东英盛生物技术有限公司 Method and kit for detecting eszopiclone content in blood and application of kit
CN113406244A (en) * 2021-08-03 2021-09-17 四川大学 Common poison screening database and rapid screening method based on liquid chromatogram-rod orbit trap mass spectrum

Also Published As

Publication number Publication date
CN107478747B (en) 2019-11-08

Similar Documents

Publication Publication Date Title
CN107478747B (en) The liquid chromatography-mass spectrography screening method of unknown poisonous substance in blood
CN104165937B (en) A kind of high efficiency liquid phase-high-resolution flight time tandem mass spectrometry detects the method for hypoglycemic in blood and blood-pressure drug
CN104133006B (en) A kind of ultra high efficiency liquid phase-mass spectroscopy detects method that is hypoglycemic in blood and blood-pressure drug
Wang et al. Quality and safety of Chinese herbal medicines guided by a systems biology perspective
Lu et al. Urinary metabonomics study on toxicity biomarker discovery in rats treated with Xanthii Fructus
Legido‐Quigley et al. Liquid chromatography–mass spectrometry methods for urinary biomarker detection in metabonomic studies with application to nutritional studies
Sora et al. Analytical issues in HPLC/MS/MS simultaneous assay of furosemide, spironolactone and canrenone in human plasma samples
Easter et al. Pharmaceutical identifier confirmation via DART-TOF
Aszyk et al. The use of HPLC-Q-TOF-MS for comprehensive screening of drugs and psychoactive substances in hair samples and several “legal highs” products
CN103235073B (en) Metabonomics analysis method base on acute anaphylactic reaction
CN105987966A (en) Quality control method for Callicarpa kwangtungensis based on the spectrum-activity relationship and method for establishing model thereof
Chan et al. Liquid chromatography/mass spectrometry for metabonomics investigation of the biochemical effects induced by aristolochic acid in rats: the use of information‐dependent acquisition for biomarker identification
Chen et al. Quantitative and chemical fingerprint analysis of Desmodium styracifolium by high-performance liquid chromatography combined with chemometrics
Shi et al. Ambient ionization mass spectrometry: application and prospective
Poklis et al. Tissue disposition of ***e in man: a report of five fatal poisonings
Bruni et al. Analytical Challenges for Identification of New Psychoactive Substances
Li et al. Mass spectrometry-sensitive probes coupled with direct analysis in real time for simultaneous sensing of chemical and biological properties of botanical drugs
Guan et al. Novel algorithms for comprehensive untargeted detection of doping agents in biological samples
Münster-Müller et al. A novel impurity-profiling workflow with the combination of flash-chromatography, UHPLC-MS, and multivariate data analysis for highly pure drugs: a study on the synthetic cannabinoid MDMB-CHMICA
Wen et al. Direct infusion electrospray ionization-ion mobility-mass spectrometry for rapid metabolite marker discovery of medicinal Phellodendron Bark
Ohbuchi et al. Differential annotation of converted metabolites (DAC-Met): Exploration of Maoto (Ma-huang-tang)-derived metabolites in plasma using high-resolution mass spectrometry
Zhang et al. An integration of UPLC‐Q‐TOF/MS and chemometrics analysis for the holistic quality evaluation of different geographical Paederia scandens
Du et al. Quantitative analysis of 17 hypoglycemic drugs in fingerprints using ultra‐high‐performance liquid chromatography/tandem hybrid triple quadrupole linear ion trap mass spectrometry
Hishimoto et al. Molecular histochemistry identifies peptidomic organization and reorganization along striatal projection units
CN107167540A (en) The method for determining the DTPA Zn in human urine biological sample

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
GR01 Patent grant
GR01 Patent grant