CN105987970B - A kind of method of flumequine enantiomer in detection human plasma - Google Patents

A kind of method of flumequine enantiomer in detection human plasma Download PDF

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CN105987970B
CN105987970B CN201610394963.3A CN201610394963A CN105987970B CN 105987970 B CN105987970 B CN 105987970B CN 201610394963 A CN201610394963 A CN 201610394963A CN 105987970 B CN105987970 B CN 105987970B
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flumequine
human plasma
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enantiomer
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杨立业
胡兆红
欧阳小琨
王阳光
金如娜
刘超
王南
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Zhejiang Ocean University ZJOU
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    • 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
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    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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    • 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
    • G01N2030/022—Column chromatography characterised by the kind of separation mechanism
    • G01N2030/027—Liquid chromatography
    • 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
    • G01N30/04—Preparation or injection of sample to be analysed
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    • G01N2030/062—Preparation extracting sample from raw material

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Abstract

The present invention relates to a kind of method of flumequine enantiomer in detection human plasma, configuration standard flumequine solution is added in human plasma, is then detected using UFLC-MS/MS to it.SPE condition is optimized in the present invention, so that the time of Solid Phase Extraction shortens, efficiency is got higher, and the concentration precision of UFLC-MS/MS analysis flumequine enantiomer is high, and speed is fast, easy to operate, cost is relatively low；Detection method is good to the linear relationship of target compound, and the rate of recovery is high, and relative deviation is small, and the reagent low toxicity used, usage amount is few, environmentally friendly.

Description

A kind of method of flumequine enantiomer in detection human plasma
Technical field
The present invention relates to a kind of methods for rapidly and efficiently detecting flumequine enantiomer in human plasma.
Background technique
Flumequine (FLU) is second generation fluoroquinolone antibacterial agent, is animal specific antibacterials, to treatment gram-negative Property bacterium infection, especially have preferably to poultry, fowl and aquatic animal disease caused by Escherichia coli, mycoplasma, Aeromonas hydrophila Curative effect.Its mechanism of action mainly inhibits DNA gyrase A subunit, destroys its activity, as a result makes DNA, core The synthesis of ribosomal ribonucleic acid and protein is disturbed, and prevents cell from being divided again, to play bactericidal effect.Since flumequine has There are high security, tolerance and unique high osmosis.Existing research discovery high dose flumequine can cause rat embryo to be developed Distortion, although there is not been reported for harm of the low dosage flumequine to human body, long-term intake has the remaining food of flumequine, dives It can not be underestimated in risk.
Flumequine is a kind of chiral drug, has an asymmetric carbon atom, two chiral enantiomers.The difference of chiral drug Different pharmacodynamics, pharmacokinetics and Toxicological Characterization are often shown between enantiomer, therefore, the different enantiomers of chiral drug Detect particularly important.Currently, it is many for residue detection research of the flumequine racemic modification in aquatic products, but do not have still Have for residue detection of the flumequine enantiomer in human plasma.Therefore, carry out flumequine enantiomer in detection human plasma to grind Study carefully, will for flumequine in human plasma remaining risk assessment and rationally, safe handling foundation is provided.
Summary of the invention
It is an object of the invention to existing crystallisation detection flumequine enantiomer is at high cost, disengaging time is long in order to solve, Applicability is narrow, complicated for operation, the not high defect of precision and provide it is a kind of quickly, precision it is high, easy to operate, lower-cost detection The method of flumequine enantiomer in human plasma.
To achieve the goals above, the invention adopts the following technical scheme:
A kind of method of flumequine enantiomer in detection human plasma, comprising the following steps:
1) use volume ratio 90%:10% isopropanol and normal heptane mixture as mobile phase by flumequine dissolution and it is dilute Release the solution for being configured to 40-50 μ g/mL, and with obtaining flumequine solution for standby after filtering with microporous membrane；Weigh 1mg Propranolol Standard items are obtained general after ultrasonic 10min with the mixture constant volume of the isopropanol of volume ratio 70%:30% and normal heptane to 100mL Naphthalene Luo Er solution saves backup at 4 DEG C；
2) it takes adult blood plasma to be placed in centrifuge tube, the flumequine solution of step 1) configuration, solid-liquid ratio 1mL:120- is added 150mL is added anhydrous cupric sulfate after oscillation and monoethanolamine, 8000-12000rpm centrifugal treating 10-15min takes supernatant, Residue is dissolved with monoethanolamine and centrifugal treating, merges supernatant, and the Propranolol of 1/2 volume of human plasma is added in supernatant Solution adds the MTBE of 30 times of volumes of human plasma, is centrifuged 5-10min at 14000rpm, obtains sample liquid；
3) hexane solution of 2-3 times of sample liquid volume is added in the sample liquid of step 2), abandon after stratification just oneself Surplus solution is crossed column extracting, is eluted after the completion of extraction with deionized water by alkane layer, and negative pressure is drained, and divides 2-5 elution, after elution Solution in nitrogen evaporator in 30-35 DEG C of water-bath, be dried with nitrogen, residue is redissolved with ethyl alcohol, micropore nanofiltration, and filtrate is spare；
4) filtrate that step 3) obtains is detected using high performance liquid chromatograph；CHIRALCEL is selected when detection OJ-RH chiral column, the filler of the chiral column are 5 μ Silica Surface coating celluloses -10-hydroxycamptothecine.In the technical program In, extracting process effect used in the present invention is good, and the time is short, reduces the consumption of reagent.
Preferably, successively using methanol, two pairs of toluyl-l- tartaric acid, the bigcatkin willow containing ferric citrate in step 3) Aqueous acid activates HLB solid-phase extraction column.
Preferably, salicylic mass fraction is 5-6.5%, the mass fraction of ferric citrate in aqueous solution of salicylic acid For 0.4-0.7%.
Preferably, step 3) eluent is the methanol solution containing volume fraction 15%, the flow velocity for crossing column is 6-9mL/ Min, eluent flow rate 1.2-1.5mL/min.
Preferably, cellulose fibre the preparation method comprises the following steps: is put into 45-55 DEG C of matter by cellulose -10-hydroxycamptothecine Measure score be 25-30% potassium hydroxide solution in, then be added 2 times of cellulose fibre quality epoxy quaternary ammonium salt compound and 5 times of cationic polyacrylamide class compounds of cellulose fibre quality are ultrasonically treated 20-30min under the power of 55-85kw, so After be warming up to 150 DEG C, 10 times of cellulose fibre quality of 10-hydroxycamptothecine is added, reacts 2-4h, is washed after cooling, use vinegar Acid is neutralized to neutrality.
Preferably, cellulose fibre is viscose rayon or cotton fiber.
Preferably, the additional amount of anhydrous cupric sulfate is 3 times of the quality of human plasma, the additional amount of monoethanolamine is 1g people 20mL is added in blood plasma.
Preferably, chromatographic condition are as follows: chromatographic column: CHIRALCEL OJ-RH；Mobile phase: water-acetonitrile (82:18, v/v, It containing volume ratio is 0.4% glacial acetic acid and 0.5% ammonium acetate in ethyl alcohol)；Flow velocity: 0.5mL/min；Detection wavelength: 294nm；Sample volume: 2 μ L；Column temperature: 40 DEG C.
Preferably, Mass Spectrometry Conditions are as follows: triplex tandem quadrupole rod Mass Spectrometry Conditions: ion mode: positive ionization electrospray mode； Ion source gas 1:60psi；Ion source gas 2:60psi；Whiff pressure: 40psi；Touch flow: 8L/min；Ionspray electricity Pressure: 5500V；Temperature: 500 DEG C
The beneficial effects of the invention are as follows the present invention to be optimized SPE condition, so that the time of Solid Phase Extraction contracts Short, efficiency is got higher, and the concentration precision of efficient liquid-phase chromatography method analysis flumequine enantiomer is high, and speed is fast, it is easy to operate, at This is lower；Detection method is good to the linear relationship of target compound, and the rate of recovery is high, and relative deviation is small, and the reagent low toxicity used makes Dosage is few, environmentally friendly.
Detailed description of the invention
Fig. 1 is the chromatogram of S- (-)-FLU in the embodiment of the present invention 1.
Fig. 2 is the chromatogram of R- (+)-FLU in the embodiment of the present invention 1.
Specific embodiment
Below by specific embodiment, the present invention will be further described.
In the present invention, if not refering in particular to, all devices and raw material is commercially available or the industry is common are following Method in embodiment is unless otherwise instructed conventional method in that art.
High performance liquid chromatograph Agilent 1200 is purchased from Agilent (China) Science and Technology Ltd.；Mass spectrograph API6500 Purchased from AB SCIEX, Ontario, Canada；Water-bath nitrogen evaporator WD-12 speeds experimental instruments and equipment limited purchased from Henan day；Solid phase Abstraction instrument HSE-12B is purchased from Tianjin Hengao Technology Development Co., Ltd.；Solid-phase extraction column Waters Oasis HLB is purchased from Hangzhoupro Zhou Jiatai scientific instrument Co., Ltd；Glacial acetic acid (analysis is pure), triethylamine (analysis is pure) are limited purchased from Chinese medicines group chemical reagent Company；Flumequine is purchased from Daicel drug chiral technology (Shanghai) Co., Ltd..
Chromatographic condition are as follows: chromatographic column: CHIRALCEL OJ-RH；Mobile phase: (82:18, v/v contain in ethyl alcohol water-acetonitrile Volume ratio is 0.4% glacial acetic acid and 0.5% ammonium acetate)；Flow velocity: 0.5mL/min；Detection wavelength: 294nm；Sample volume: 2 μ L；Column temperature: 40 DEG C.
Mass Spectrometry Conditions are as follows: triplex tandem quadrupole rod Mass Spectrometry Conditions: ion mode: positive ionization electrospray mode；Ion source gas Body 1:60psi；Ion source gas 2:60psi；Whiff pressure: 40psi；Touch flow: 8L/min；Ion spray voltage: 5500V； Temperature: 500 DEG C.
Embodiment 1
A kind of method of flumequine enantiomer in detection human plasma, comprising the following steps:
1) use volume ratio 90%:10% isopropanol and normal heptane mixture as mobile phase by flumequine dissolution and it is dilute Release the solution for being configured to 40 μ g/mL, and with obtaining flumequine solution for standby after filtering with microporous membrane；Weigh 1mg Propranolol mark Quasi- product obtain general naphthalene after ultrasonic 10min with the mixture constant volume of the isopropanol of volume ratio 70%:30% and normal heptane to 100mL Luo Er solution saves backup at 4 DEG C；
2) it takes adult blood plasma to be placed in centrifuge tube, the flumequine solution of step 1) configuration is added, solid-liquid ratio 1mL: Anhydrous cupric sulfate and monoethanolamine, 8000rpm centrifugal treating 10min is added in 120mL after oscillation, take supernatant, the single second of residue Hydramine dissolution and centrifugal treating, merge supernatant, the Propranolol solution of addition 1/2 volume of human plasma in supernatant, then plus The MTBE for entering 30 times of volumes of human plasma is centrifuged 5min at 14000rpm, obtains sample liquid；The additional amount of anhydrous cupric sulfate is behaved 3 times of the quality of blood plasma, the additional amount of monoethanolamine are that 20mL is added in 1g human plasma；
3) 2 times of sample liquid volume of hexane solution is added in the sample liquid of step 2), abandons n-hexane after stratification Layer, crosses column extracting for surplus solution, is eluted after the completion of extraction with deionized water, and negative pressure is drained, point 2 elutions, molten after elution Liquid in 30 DEG C of water-baths, is dried with nitrogen in nitrogen evaporator, and residue is redissolved with ethyl alcohol, micropore nanofiltration, and filtrate is spare；Successively use first Alcohol, two pairs of toluyl-l- tartaric acid, the aqueous solution of salicylic acid containing ferric citrate activate HLB solid-phase extraction column；Bigcatkin willow sour water Salicylic mass fraction is 5% in solution, and the mass fraction of ferric citrate is 0.4%；Eluent is containing volume fraction 15% methanol solution, the flow velocity for crossing column is 6mL/min, eluent flow rate 1.2mL/min；
4) filtrate that step 3) obtains is detected using UFLC-MS/MS；CHIRALCEL OJ-RH is selected when detection Chiral column, the filler of the chiral column are 5 μ Silica Surface coating celluloses -10-hydroxycamptothecine.
Viscose rayon -10-hydroxycamptothecine the preparation method comprises the following steps: be by the mass fraction that viscose rayon is put into 45-55 DEG C In 25% potassium hydroxide solution, 2 times of viscose rayon quality of epoxy quaternary ammonium salt compound and viscose rayon quality 5 is then added Times cationic polyacrylamide class compound is ultrasonically treated 20min under the power of 55kw, then heats to 150 DEG C, viscose glue is added The 10-hydroxycamptothecine that 10 times of fiber quality reacts 2h, washes after cooling, be neutralized to neutrality with acetic acid.
Embodiment 2
A kind of method of flumequine enantiomer in detection human plasma, comprising the following steps:
1) use volume ratio 90%:10% isopropanol and normal heptane mixture as mobile phase by flumequine dissolution and it is dilute Release the solution for being configured to 45 μ g/mL, and with obtaining flumequine solution for standby after filtering with microporous membrane；Weigh 1mg Propranolol mark Quasi- product obtain general naphthalene after ultrasonic 10min with the mixture constant volume of the isopropanol of volume ratio 70%:30% and normal heptane to 100mL Luo Er solution saves backup at 4 DEG C；
2) it takes adult blood plasma to be placed in centrifuge tube, the flumequine solution of step 1) configuration is added, solid-liquid ratio 1mL: Anhydrous cupric sulfate and monoethanolamine, 10000rpm centrifugal treating 12min is added in 130mL after oscillation, take supernatant, and residue is single Ethanol amine dissolution and centrifugal treating, merge supernatant, and the Propranolol solution of 1/2 volume of human plasma is added in supernatant, then The MTBE of 30 times of volumes of human plasma is added, is centrifuged 7min at 14000rpm, obtains sample liquid；The additional amount of anhydrous cupric sulfate is 3 times of the quality of human plasma, the additional amount of monoethanolamine are that 20mL is added in 1g human plasma；
3) 3 times of sample liquid volume of hexane solution is added in the sample liquid of step 2), abandons n-hexane after stratification Layer, crosses column extracting for surplus solution, is eluted after the completion of extraction with deionized water, and negative pressure is drained, point 3 elutions, molten after elution Liquid in 32 DEG C of water-baths, is dried with nitrogen in nitrogen evaporator, and residue is redissolved with ethyl alcohol, micropore nanofiltration, and filtrate is spare；Successively use first Alcohol, two pairs of toluyl-l- tartaric acid, the aqueous solution of salicylic acid containing ferric citrate activate HLB solid-phase extraction column；Bigcatkin willow sour water Salicylic mass fraction is 5.8% in solution, and the mass fraction of ferric citrate is 0.5%；Eluent is containing volume fraction 15% methanol solution, the flow velocity for crossing column is 7mL/min, eluent flow rate 1.3mL/min；
4) filtrate that step 3) obtains is detected using UFLC-MS/MS；CHIRALCEL OJ-RH is selected when detection Chiral column, the filler of the chiral column are 5 μ Silica Surface coating celluloses -10-hydroxycamptothecine.
Viscose rayon -10-hydroxycamptothecine is the preparation method comprises the following steps: be 28% by the mass fraction that viscose rayon is put into 50 DEG C Potassium hydroxide solution in, 2 times of viscose rayon quality 5 times of sun of epoxy quaternary ammonium salt compound and viscose rayon quality are then added Cationic polyacrylamide class compound is ultrasonically treated 25min under the power of 65kw, then heats to 150 DEG C, and viscose rayon is added The 10-hydroxycamptothecine that 10 times of quality reacts 3h, washes after cooling, be neutralized to neutrality with acetic acid.
Embodiment 3
A kind of method of flumequine enantiomer in detection human plasma, comprising the following steps:
1) use volume ratio 90%:10% isopropanol and normal heptane mixture as mobile phase by flumequine dissolution and it is dilute Release the solution for being configured to 50 μ g/mL, and with obtaining flumequine solution for standby after filtering with microporous membrane；Weigh 1mg Propranolol mark Quasi- product obtain general naphthalene after ultrasonic 10min with the mixture constant volume of the isopropanol of volume ratio 70%:30% and normal heptane to 100mL Luo Er solution saves backup at 4 DEG C；
2) it takes adult blood plasma to be placed in centrifuge tube, the flumequine solution of step 1) configuration is added, solid-liquid ratio 1mL: Anhydrous cupric sulfate and monoethanolamine, 12000rpm centrifugal treating 10-15min is added in 150mL after oscillation, take supernatant, and residue is used Monoethanolamine dissolution and centrifugal treating, merge supernatant, and the Propranolol solution of 1/2 volume of human plasma is added in supernatant, The MTBE for adding 30 times of volumes of human plasma is centrifuged 10min at 14000rpm, obtains sample liquid；The addition of anhydrous cupric sulfate Amount is 3 times of the quality of human plasma, and the additional amount of monoethanolamine is that 20mL is added in 1g human plasma；
3) 3 times of sample liquid volume of hexane solution is added in the sample liquid of step 2), abandons n-hexane after stratification Layer, crosses column extracting for surplus solution, is eluted after the completion of extraction with deionized water, and negative pressure is drained, point 5 elutions, molten after elution Liquid in 35 DEG C of water-baths, is dried with nitrogen in nitrogen evaporator, and residue is redissolved with ethyl alcohol, micropore nanofiltration, and filtrate is spare；Successively use first Alcohol, two pairs of toluyl-l- tartaric acid, the aqueous solution of salicylic acid containing ferric citrate activate HLB solid-phase extraction column；Bigcatkin willow sour water Salicylic mass fraction is 6.5% in solution, and the mass fraction of ferric citrate is 0.7%；Eluent is containing volume fraction 15% methanol solution, the flow velocity for crossing column is 9mL/min, eluent flow rate 1.5mL/min；
4) filtrate that step 3) obtains is detected using UFLC-MS/MS；CHIRALCEL OJ-RH is selected when detection Chiral column, the filler of the chiral column are 5 μ Silica Surface coating celluloses -10-hydroxycamptothecine.
Cotton fiber -10-hydroxycamptothecine is the preparation method comprises the following steps: be put into 55 DEG C of mass fraction for cotton fiber as 30% hydrogen In potassium oxide solution, 2 times of cotton quality 5 times of cations of epoxy quaternary ammonium salt compound and cotton quality poly- third are then added Acrylamide compound is ultrasonically treated 30min under the power of 85kw, then heats to 150 DEG C, is added 10 times of cotton quality 10-hydroxycamptothecine reacts 2-4h, washes after cooling, be neutralized to neutrality with acetic acid.
The chromatogram of the embodiment of the present invention 1 is shown in Fig. 1.
After high performance liquid chromatograph detects, peak area is recorded, using the concentration of flumequine enantiomer as abscissa, with opposite The peak area answered is ordinate, carries out linear fit, S- (-)-using Analyst 1.6.2software from AB SCIEX The regression equation of FLU and R- (+)-FLU.As can be seen from the results, R2Greater than 0.995, S- (-)-FLU and R- (+)-FLU in 0.5ng/ It is linear good within the scope of ml-500ng/ml.
The regression equation of S- (-)-FLU: 0.9969 range of linearity of y=0.584x-0.00935 related coefficient (ng/ml) 0.5-500。
The regression equation of R- (+)-FLU: 0.9960 range of linearity of y=0.623x+0.0542 related coefficient (ng/ml) 0.5- 500。

Claims (9)

1. a kind of method of flumequine enantiomer in detection human plasma, which comprises the following steps:
1) flumequine is dissolved as solvent and dilutes preparation by the mixture of the isopropanol and normal heptane of using volume ratio 90%:10% At the solution of 40-50 μ g/mL, and with obtaining flumequine solution for standby after filtering with microporous membrane；Weigh 1mg Propranolol mark Quasi- product are obtained general after ultrasonic 10min with the mixture constant volume of the isopropanol of volume ratio 70%:30% and normal heptane to 100mL Naphthalene Luo Er solution saves backup at 4 DEG C；
2) it takes adult blood plasma to be placed in centrifuge tube, the flumequine solution that step 1) is prepared, solid-liquid ratio 1mL:120- is added 150mL is added anhydrous cupric sulfate after oscillation and monoethanolamine, 8000-12000rpm centrifugal treating 10-15min takes supernatant Liquid, residue is dissolved with monoethanolamine and centrifugal treating, merges supernatant, and the general of 1/2 volume of human plasma is added in supernatant Naphthalene Luo Er solution, adds the MTBE of 30 times of volumes of human plasma, is centrifuged 5-10min at 14000rpm, obtains sample Liquid；
3) hexane solution of 2-3 times of sample liquid volume is added in the sample liquid of step 2, abandons n-hexane after stratification Layer, crosses column extracting for surplus solution, is eluted after the completion of extraction with deionized water, and negative pressure is drained, and divides 2-5 elution, after elution Solution in nitrogen evaporator in 30-35 DEG C of water-bath, be dried with nitrogen, residue is redissolved with ethyl alcohol, filtering with microporous membrane, filtrate It is spare；
4) filtrate that step 3) obtains is detected using UFLC-MS/MS；CHIRALCEL OJ-RH is selected when detection Chiral column, the filler of the chiral column are 5 μ Silica Surface coating celluloses -10-hydroxycamptothecine；Mobile phase: water-acetonitrile body Product than be 82:18, wherein in acetonitrile containing volume ratio be 0.4% glacial acetic acid and 0.5% ammonium acetate, flow velocity: 0.5 mL/ min。
2. the method for flumequine enantiomer in a kind of detection human plasma described according to claim 1, which is characterized in that step It is rapid 3) in, successively activate HLB with methanol, two pairs of toluyl-l- tartaric acid, aqueous solution of salicylic acid containing ferric citrate Solid-phase extraction column.
3. the method for flumequine enantiomer in a kind of detection human plasma according to claim 2, which is characterized in that bigcatkin willow Salicylic mass fraction is 5-6.5% in aqueous acid, and the mass fraction of ferric citrate is 0.4-0.7%.
4. according to claim 1 or described in 2 in a kind of detection human plasma flumequine enantiomer method, feature exists In step 3 eluent is the methanol solution of volume fraction 15%, and the flow velocity for crossing column is 6-9mL/min, and eluent flow rate is 1.2-1.5mL/min。
5. the method for flumequine enantiomer in a kind of detection human plasma described according to claim 1 or 2 or 3, special Sign is that cellulose -10-hydroxycamptothecine the preparation method comprises the following steps: be by the mass fraction that cellulose fibre is put into 45-55 DEG C In the potassium hydroxide solution of 25-30%, 2 times of cellulose fibre quality of epoxy quaternary ammonium salt compound and cellulose is then added 5 times of cationic polyacrylamide class compounds of fiber quality are ultrasonically treated 20-30min under the power of 55-85kw, then 150 DEG C are warming up to, 10 times of cellulose fibre quality of 10-hydroxycamptothecine is added, 2-4h is reacted, is washed after cooling, used Acetic acid is neutralized to neutrality.
6. the method for flumequine enantiomer in a kind of detection human plasma according to claim 5, which is characterized in that fiber Cellulose fiber is viscose rayon or cotton fiber.
7. the method for flumequine enantiomer in a kind of detection human plasma described according to claim 1 or 2 or 3, special Sign is that the additional amount of anhydrous cupric sulfate is 3 times of the quality of human plasma, and the additional amount of monoethanolamine is that 1g human plasma adds Enter 20mL.
8. the method for flumequine enantiomer in a kind of detection human plasma described according to claim 1 or 2 or 3, special Sign is, chromatographic condition are as follows: chromatographic column: CHIRALCEL OJ-RH；Detection wavelength: 294 nm；Sample volume: 2 μ L；Column temperature: 40 ℃。
9. the method for flumequine enantiomer in a kind of detection human plasma described according to claim 1 or 2 or 3, special Sign is, Mass Spectrometry Conditions are as follows: triplex tandem quadrupole rod Mass Spectrometry Conditions: ion mode: positive ionization electrospray mode；Ion source gas 1:60 psi；Ion source gas 2:60psi；Whiff pressure: 40psi；Touch flow: 8L/min；Ion spray voltage: 5500 V； Temperature: 500 DEG C.
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