CN106770883B - A kind of fluorine [18F] change sodium injection top coal drawing thin layer chromatography - Google Patents
A kind of fluorine [18F] change sodium injection top coal drawing thin layer chromatography Download PDFInfo
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Abstract
The invention belongs to thin-layer chromatographic analysis fields, and in particular to a kind of fluorine [18F] change sodium injection top coal drawing thin layer chromatography.Described method includes following steps: (1) point sample at one end 2-3cm of the stationary phase by electrolyte solution processing；(2) stationary phase is put into after drying in the chromatography cylinder for filling mobile phase, point sample one end of stationary phase is made to immerse deep about 1-2cm in solvent；(3) solvent front to 8-10cm when take out stationary phase, dried up with hair dryer cold wind；(4) radiocounting is measured on radioactivity chromatograph scanner, calculates its RfValue and radiochemicsl purity；(5) according to RfValue and the peak shape of main peak select suitable condition.Electrolyte solution used be mass percentage concentration be 1%-3% sodium acetate solution, aluminum potassium sulfate solution, sodium chloride solution, sodium carbonate liquor, any one of sodium bicarbonate solution.It can be by radioactivity main peak R with technical solution of the present inventionfValue is deployed into 0.7-0.8, can incite somebody to action [18F] fluorine ion and other radioimpurity radioactive impurities efficiently separate.
Description
Technical field
The invention belongs to thin-layer chromatographic analysis fields, and in particular to a kind of fluorine [18F] change sodium injection top coal drawing thin layer color
Spectral analysis method.
Background technique
Fluorine [18F] to change sodium injection be a kind of positron computer layer imaging (Positron Emission
Tomography, PET) drug, it is mainly used for the diagnosis of active osteoblastic reaction bone disease.Early in Blau in 1962 etc.]Just
It was found that it is a kind of excellent skeletal imaging agent, U.S. Food and Drug Administration (Food and Drug in 1972
Administration, FDA) approval18F- is fluorinated sodium injection for clinic, but 1975 supply because business reason suspends market
It answers.In recent years, due to the fast development of PET and PET/CT technology,18F- sodium fluoride PET imaging superiority and99Mo/99TcmHair
Raw device99The global supply of material shortage that Mo raw material faces, it is right in the world18F- sodium fluoride is for the research of Bone scans and using again
Cause the attention of scholars.
Fluorine [18F] change a kind of positron medicine of the sodium injection as intravenous injection, quality controls the safety to drug
There is very important meaning with validity.Its method of quality control is included in United States Pharmacopeia and European Pharmacopoeia.Wherein putting
Pure measurement method is mainly the chromatography of ions and high performance liquid chromatography (high performance liquid
Chromatography, HPLC).Wherein method used in United States Pharmacopeia is the chromatography of ions, and detector is Conductivity detection
Device and radioactive detector, mobile phase are 0.003mol/L sulfuric acid, flow velocity 0.8mL/min, chromatographic column L17 chromatographic column；Europe
Method used in pharmacopeia is high performance liquid chromatography, and detector is 220nm UV detector and radioactive detector, flowing
It is mutually 4g/L NaOH solution, flow velocity 1mL/min, column temperature is 20~30 DEG C, and chromatographic column is strong-base anion-exchange resin
Column.Although the chromatography of ions and high performance liquid chromatography are a kind of more accurate measurement methods, but operate relative complex, analysis
Time is long.And18F label positron medicine due to nucleic half-life period it is short, validity period is short, need to detect as early as possible after production and
Delivery.Therefore, establish method easy to operate, that analysis time is short to fluorine [18F] change the measurement of sodium injection top coal drawing with very
Important meaning.
Thin-layered chromatography (Thin Layer Chromatography, TLC) is a kind of relatively rapid, convenient top coal drawing
Analysis method is usually used in the top coal drawing analysis of some short-half-life radioactive drugs, such as [18F] FDG top coal drawing analysis just use
Thin-layered chromatography.Nandy etc. report using tlc determination fluorine [18F] change sodium injection top coal drawing method, but this report
Using silica gel plate as stationary phase, 95% acetonitrile is as mobile phase, and radioactivity main peak is substantially in origin, RfValue is 0.0-
0.12, there is no effectively expansion, and there are the possibility that some impurity do not separate.
Summary of the invention
For the problems in background technique, the present invention provides one kind can easily and fast detect fluorine [18F] change sodium injection
The thin layer chromatography of liquid top coal drawing.The present invention uses a variety of different stationary phases and mobile phase, and uses different electricity
After electrolyte solution handles chromatograph paper, several suitable conditions have finally been determined, radioactivity main peak can be deployed into Rf
Value 0.7-0.8, can incite somebody to action [18F] fluorine ion and other radioimpurity radioactive impurities efficiently separate.
To achieve the above object, the following technical solutions are proposed by the present invention:
A kind of fluorine [18F] change sodium injection top coal drawing thin layer chromatography, described method includes following steps:
(1) point sample at the 2-3cm of stationary phase one end；(2) stationary phase is put into after drying in the chromatography cylinder for filling mobile phase, makes stationary phase
Point sample one end immerse deep about 1-2cm in solvent；(3) solvent front to 8-10cm when take out stationary phase, it is cold with hair dryer
Wind is dry；(4) radiocounting is measured on radioactivity chromatograph scanner, calculates its Rf value RfValue and radiochemical purity；
(5) according to RfValue and the peak shape of main peak select suitable condition；
The stationary phase is pre-processed by electrolyte solution, and the electrolyte solution is that mass percentage concentration is 1%-3%
Sodium acetate solution, aluminum potassium sulfate solution, sodium chloride solution, sodium carbonate liquor, any one of sodium bicarbonate solution；
The RfThe calculation method of value are as follows:
Rf=a/h (1)
In formula, a is distance of the origin to spot centers；H is distance of the origin to solvent front；
The calculation method of the radiochemical purity are as follows: putting chemical purity=main peak peak area/total peak area.
Further, the stationary phase uses silica G plate, Flash silica paper, Whatman No.1 chromatograph paper.
Further, the mobile phase uses V (acetonitrile): V (water)=38:2~12:28；V (acetonitrile): V (physiology salt
Water)=20:20；V (methanol): V (water)=17:3~0.5:100；V (methanol): V (physiological saline)=20:20；V (ethyl alcohol): V
(water)=20:20；V (acetone): V (water)=25:5~25:10.
Further, the NaOH solution of 0.05mol/L is added in the mobile phase, main peak can be improved on chromatograph paper
Trailing phenomenon.
Further, the method calculates separating degree R using following formula:
tR1、tR1The retention time at respectively two neighboring peak；W1、W2The peak width at respectively two neighboring peak.
The beneficial effects of the present invention are:
The present invention provides it is a kind of it is more convenient, more quickly detection fluorine [18F] change sodium injection top coal drawing thin-layer chromatography
Analysis method.After handling using different electrolyte solutions chromatograph paper, several suitable conditions have finally been determined, it can
Radioactivity main peak is deployed into RfValue 0.7-0.8, can incite somebody to action [18F] fluorine ion and other radioimpurity radioactive impurities efficiently separate.With it is traditional
Separation method is compared, and method provided by the invention not only solves radioactivity main peak substantially in origin, is not unfolded effectively, exists
Some impurity do not separate possible problem, achieve the effect that odds and ends matter；Solve main peak simultaneously has hangover existing on chromatograph paper
As certain density aqueous slkali, available better peak shape are added in expansion system.
Detailed description of the invention
Fig. 1 flowing is added the chromatogram that alkali systems obtain；
Fig. 2 is the chromatogram that mobile phase acid adding system obtains；
Fig. 3 is the not preprocessed obtained chromatogram of chromatograph paper；
Fig. 4 is the chromatogram that chromatograph paper is handled through sodium acetate solution；
Fig. 5 is the chromatogram that chromatograph paper is handled through aluminum potassium sulfate solution；
Fig. 6 is the chromatogram that chromatograph paper is handled through sodium chloride solution；
Fig. 7 is the chromatogram that chromatograph paper is handled through sodium carbonate liquor；
Fig. 8 is the chromatogram that chromatograph paper is handled through sodium bicarbonate solution；
Fig. 9 is that the sodium acetate solution that mass percentage concentration is 1% handles the chromatogram obtained after chromatograph paper；
Figure 10 is that the sodium acetate solution that mass percentage concentration is 2% handles the chromatogram obtained after chromatograph paper；
Figure 11 is that the sodium acetate solution that mass percentage concentration is 3% handles the chromatogram obtained after chromatograph paper.
Specific embodiment
For the ease of further appreciating that examples provided below has done more detailed description to it to of the invention.This
A little embodiments are only not supposed to be a limitation to the present invention for narration or implementation principle, and protection scope of the present invention is still with right
Subject to it is required that.
Embodiment 1
Make stationary phase with different materials, is equipped with corresponding mobile phase and is screened, the results are shown in Table 1.It can by data in table
Know, system 11,14,21 can by impurity and fluorine [18F] change sodium efficiently separate, the R at two peaksfValue is also appropriate, but system 11,21 is dragged
Tail is more serious, therefore finally determines optimal TLC condition are as follows: stationary phase is Whatman No.1, and mobile phase is V (methanol): V
The expansion system of (water)=20:20.
The different expansion system TLC results of table 1
Embodiment 2
Since, through analyzing it is found that main peak has trailing phenomenon on chromatograph paper, peak is slightly wide after using system 14 to be unfolded.It is terrible
To better peak shape, improving hangover, attempts that system addition acid or alkali is being unfolded, adjust solvent pH value, situation is unfolded in observation,
As a result table 2, Fig. 1 and Fig. 2 are listed in.Through analysis it is found that the hangover slightly improvement under alkaline system, preferred mobile phase are V (first
Alcohol): V (water): V (0.05mol/LNaOH)=20:20:1.Fluoride impurities peak becomes smaller under acid system, it may be possible to due to
Partially fluorinated object impurity reacts with acid, with principal product fluorine [18F] change sodium be expanded to forward position together.
Influence of the same expansion system different pH values of table 2 to TLC analysis result
Embodiment 3
After the present invention is handled Whatman No.1 chromatograph paper with following several electrolyte solutions, with V (methanol): V
The expansion system of (water)=20:20 be mobile phase respectively to fluorine [18F] change sodium top coal drawing analyzed.1) mass percentage concentration is
1% sodium acetate solution；2) aluminum potassium sulfate solution that mass percentage concentration is 1%；3) chlorine that mass percentage concentration is 0.9%
Change sodium solution；4) sodium carbonate liquor that mass percentage concentration is 1%；5) sodium bicarbonate solution that mass percentage concentration is 1%.
Corresponding chromatogram is as shown in Fig. 3, Fig. 4, Fig. 5, Fig. 6, Fig. 7, Fig. 8.As seen from the figure, molten with sodium acetate, sodium chloride and sodium carbonate
Liquid is best to effect is unfolded after the processing of Whatman No.1 chromatograph paper, hangover can be effectively reduced, wherein with sodium acetate solution exhibition
It is more preferable to open rear effect.
Embodiment 4
In order to further optimize to experiment condition, it is 1%, 2%, 3% 3 that the present invention uses mass percentage concentration respectively
After the sodium acetate solution of kind various concentration handles Whatman No.1 chromatograph paper, with V (methanol): V (water)=20:20
Expansion system be mobile phase respectively to fluorine [18F] change sodium top coal drawing analyzed.Corresponding chromatogram such as Fig. 9, Figure 10, Figure 11
It is shown, as seen from the figure, Whatman No.1 chromatograph paper after being handled with the sodium acetate solution that mass percentage concentration is 2%, in V (first
Alcohol): the expansion effect under V (water)=20:20 expansion system is more preferable.
After the completion of above embodiments, radiocounting is measured on radioactivity chromatograph scanner, calculates its RfIt is worth and putting
Purity.And the precision of method, the precision of system, the specificity of method and separating degree are separately verified using the above method.
1) method precision: shining experimental method, parallel point sample 6 times respectively, measures top coal drawing data, it is inclined to calculate relative standard
Difference, precision≤2.0% of method are qualification.
2) system precision: using a paper slip (1) number in 1, it is placed on replication 6 on radioactivity chromatograph scanner
It is secondary, with the top coal drawing data measured, relative standard deviation is calculated, precision≤2.0% of system is qualification.
3) specificity: the R of six experiments in the precision of methodfValue and RfThe average value of value is compared, RfValue
It should be between 0.7-0.8.
4) separating degree: with method precision test in the result analyzed carried out calculating separating degree R, separating degree with following equation
It should be greater than 2.0.
tR1、tR1The retention time at respectively two neighboring peak；W1、W2The peak width at respectively two neighboring peak.
Claims (2)
1. a kind of fluorine [18F] change sodium injection top coal drawing thin layer chromatography, described method includes following steps: (1) existing
Point sample at the 2-3cm of stationary phase one end；(2) stationary phase is put into after drying in the chromatography cylinder for filling mobile phase, makes the point of stationary phase
Depth 1-2cm in solvent is immersed in sample one end；(3) solvent front to 8-10cm when take out stationary phase, dried up with hair dryer cold wind；
(4) radiocounting is measured on radioactivity chromatograph scanner, calculates its Rf value RfValue and radiochemical purity；(5) according to Rf
Value and the peak shape of main peak select suitable condition；It is characterized by:
The stationary phase is pre-processed by electrolyte solution, and the electrolyte solution is the acetic acid that mass percentage concentration is 1%-3%
Any one of sodium solution, sodium chloride solution, sodium carbonate liquor；
The RfThe calculation method of value are as follows:
Rf=a/h (1)
In formula, a is distance of the origin to spot centers；H is distance of the origin to solvent front；
The calculation method of the radiochemical purity are as follows: putting chemical purity=main peak peak area/total peak area；
The NaOH solution of 0.05mol/L is added in the mobile phase, improves trailing phenomenon of the main peak on chromatograph paper；
The stationary phase uses Flash silica paper, and the mobile phase uses V (acetonitrile): V(water)=30:10~20:20；
Alternatively, the stationary phase uses Whatman No.1 chromatograph paper, the mobile phase uses V (methanol): V(water)=17:3, V
(methanol): V(water)=20:20, V (methanol): V(physiological saline)=20:20, V (ethyl alcohol): V(water)=20:20, V (methanol): V(ammonia
Water): V(water)=0.5:2:100.
2. a kind of fluorine according to claim 1 [18F] change sodium injection top coal drawing thin layer chromatography, feature
Be: the method calculates separating degree R using following formula:
(2)
tR1、tR1The retention time at respectively two neighboring peak； W1、W2The peak width at respectively two neighboring peak.
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| CN110018268A (en) * | 2018-01-08 | 2019-07-16 | 南京江原安迪科正电子研究发展有限公司 | It is a kind of18The thin layer chromatography of F-NaF injection top coal drawing |
| CN110879270A (en) * | 2019-11-13 | 2020-03-13 | 原子高科股份有限公司 | Fluorine [ 2 ]18F]High performance liquid chromatography analysis method for sodium chloride injection |
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| US7741121B2 (en) * | 2006-08-24 | 2010-06-22 | Siemens Medical Solutions Usa, Inc. | System for purification and analysis of radiochemical products yielded by microfluidic synthesis devices |
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