阅读说明：本技术 一种尿素c-14胶囊中c-14的放射性核纯度分析方法 (Method for analyzing purity of C-14 radioactive nuclide in urea C-14 capsule ) 是由 杨永刚 卿晶 戴雄新 魏翠雯 王小明 王春玲 张辉 陈坚明 马彦 张利利 于 2021-09-08 设计创作，主要内容包括：本发明属于放射性物质分析技术领域,涉及一种尿素[～(14)C]胶囊中～(14)C的放射性核纯度分析方法。所述的分析方法基于TDCR Cerenkov测量技术,包括如下步骤：(1)拟合关系曲线的获得；(2)样品测量；(3)结果计算。利用本发明的尿素[～(14)C]胶囊中～(14)C的放射性核纯度分析方法,能够基于TDCR Cerenkov测量技术,在准确校正～(60)Co的Cerenkov探测效率的基础上操作简单的准确分析尿素[～(14)C]胶囊中～(14)C的放射性核纯度。(The invention belongs to the technical field of radioactive substance analysis, and relates to urea [ alpha ], [ beta ] -cyclodextrin 14 C]In capsules 14 C radionuclide purity analysis method. The analysis method is based on TDCR Cerenkov measurement technology and comprises the following steps: (1) obtaining a fitting relation curve; (2) measuring a sample; (3) and (6) calculating a result. The urea [ 2 ] of the present invention is used 14 C]In capsules 14 The radioactive nuclear purity analysis method of C can be based on TDCR Cerenkov measurement technique and can be used for accurate correction 60 Accurate analysis of urea [ 2 ] with simple operation on the basis of Cerenkov detection efficiency of Co 14 C]In capsules 14 Radionuclide purity of C.)

1. Urea (alpha-amino acid)¹⁴C]In capsules¹⁴The radionuclide purity analysis method of C is characterized in that: the analysis method is based on TDCR Cerenkov measurement technology and comprises the following steps:

(1) obtaining a fitting relation curve: adding different amounts of yellow pigment solution into different liquid flash bottles, respectively adding HCl solution, mixing well to obtain different simulation samples, measuring blank Cerenkov count of different simulation samples with liquid flash instrument, and respectively adding a certain amount of yellow pigment solution into each simulation sample⁶⁰Co, measuring again the Cerenkov counts of the different mock samples with a scintillation counter and calculating the number of each mock sample⁶⁰Co detection efficiency, TDCR value, obtaining fitting on the basis⁶⁰Cerenkov detection efficiency epsilon of Co versus net TDCR value;

(2) sample measurement: taking urea¹⁴C]Dissolving in water to obtain a sample, measuring with a liquid scintillation meter, and calculating¹⁴C, measuring Cerenkov count of the actually measured sample by using a liquid scintillation meter, obtaining the detection efficiency of the actually measured sample through the fitting relation curve obtained in the step (1), and further calculating the activity concentration of the actually measured sample⁶⁰Activity concentration of Co;

(3) and (4) calculating a result: in the measured sample obtained in the step (2)¹⁴Activity concentration of C and⁶⁰calculating the activity concentration of Co to obtain urea¹⁴C]In capsules¹⁴Radionuclide purity of C.

2. The analytical method of claim 1, wherein: in the step (1), the yellow pigment solution is a lemon yellow solution.

3. The analytical method of claim 1, wherein: in the step (1), adding the analogue sample per ml⁶⁰The amount of Co is 5.0-50 Bq.

4. The analytical method of claim 1, wherein in step (1), the step (2)⁶⁰The Co detection efficiency is calculated by the formula:

wherein:

ε^60Cois composed of⁶⁰Co detection efficiency;

Dbl_sis composed of⁶⁰Double counting of the Co samples;

Dbl_bdouble counting for blank samples;

t is the measurement time of the sample;

A₀is composed of⁶⁰Theoretical value of Co activity.

5. The analysis method according to claim 1, wherein in step (1), the TDCR value is calculated by the formula:

wherein:

TDCR_netis the net TDCR value;

Dbl_sand Tpl_sDouble and triple counts of the sample;

Dbl_band Tpl_bDouble and triple counts of blank samples.

6. The analytical method according to claim 1, wherein in step (3), urea [ sic ], [ solution ] is used¹⁴C]In capsules¹⁴The calculation formula of the radionuclide purity of C is as follows:

7. the analytical method of claim 1, wherein: the liquid scintillation meter is a Hidex300SL liquid scintillation meter.

8. The analytical method of claim 1, wherein: the measuring time of the liquid scintillation meter is 20-60 minutes.

Technical Field

The invention belongs to the technical field of radioactive substance analysis, and relates to urea [ alpha ], [ beta ] -cyclodextrin¹⁴C]In capsules¹⁴C radionuclide purity analysis method.

Background

Helicobacter pylori (Hp) can cause a variety of gastric diseases and has been classified as the first carcinogenic factor by the world health organization. Research on diagnosis and treatment methods of Hp is being conducted in all countries of the world. The carbon-14 breath test is a Hp diagnostic method consistently recommended by experts at home and abroad at present, has the advantages of high sensitivity, strong special shape, no pain, no wound, rapidness, convenience and no cross infection, and is widely popularized and used clinically. When the patient takes the composition¹⁴C]After encapsulation, if the stomach of the patient is infected with Hp, Hp may produce highly active urease to hydrolyze urea to ammonia and¹⁴c-labelled CO₂Gas, CO₂Into the blood and out of the breath by detecting the presence of the breath¹⁴C-labelled CO₂The content of (A) can be used for judging whether the helicobacter pylori infection exists in the patient.

To ensure urea 2¹⁴C]The quality of capsule medicine needs to be detected and measured in raw material medicine and preparation¹⁴Purity and impurities of CThe content of (a). Urea is specifically required in the United States Pharmacopeia (USP)¹⁴C]In capsules¹⁴The purity of the radioactive nucleus of C is not less than 99.9%, and the liquid scintillation counter is used to complete the urea solution¹⁴C]And (4) measuring the purity of the radioactive nuclide in the capsule.

According to¹⁴C and¹⁴process for preparing urea, urea¹⁴C]The potential radionuclide impurities contained in the capsule mainly include⁵⁵Fe、³⁵S、⁴⁵Ca and⁶⁰and (3) Co. Wherein the content of the first and second substances,³⁵s and⁴⁵ca is a low-energy beta nuclide with short half-life period, and the maximum beta decay energy is slightly higher than that¹⁴C, their dietary dose coefficient is also equal to¹⁴C is close to;⁵⁵fe is an electron capture nuclide, and the feed dose coefficient of the Fe is obviously lower than that of the Fe¹⁴C; while⁶⁰Co is a high-energy beta-gamma nuclide with a half-life of 5.27 years, and the intake dose coefficient ratio of Co¹⁴C is more than 5 times higher. Combining the chemical purity, irradiation and cooling time of the high-purity aluminum nitride raw material¹⁴C]The urea capsule production process and the dosage evaluation result,⁶⁰co is most likely to account for the dose contribution of the impure nuclide, and needs to be measured with emphasis to ensure that the urea is used¹⁴C]The radioactive nuclear purity of the capsule meets the requirement. When in the capsule¹⁴C has purity of radionuclide not less than 99.9%, and contains impurity nuclide (especially C⁶⁰Co) will not exceed the intake dose¹⁴C itself caused 1% of the dose.

When the velocity of a particle is greater than the propagation velocity of light in the medium, the particle produces Cerenkov light that can be directly detected by the photomultiplier tube. In aqueous solution, the energy threshold for generating Cerenkov light is 0.263 MeV. Cerenkov measurement technology can avoid low-energy beta nuclide, Alpha nuclide interference and high activity in urea capsule¹⁴C bremsstrahlung background generated.⁶⁰Co belongs to a high-energy beta-gamma nuclide, 99.88 percent of the maximum beta decay energy in a beta decay branch is 317.88keV, and the optical efficiency of the generated Cerenkov is very low; and their gamma decay (branch ratio) of 1173keV and 1332keV>99.8%) can induce high energy compton electrons with energies above 0.263MeV, thereby producing Cerenkov light.¹⁴C is lowBeta-capable nuclides, do not produce Cerenkov light in aqueous solutions, but produce continuous x-ray spectra by bremsstrahlung. Based on the Cerenkov measurement technology, the chemical separation treatment is not needed, the scintillation liquid is not needed to be added into the sample, and the commercial liquid scintillation counter can be used for directly measuring the urea [ 2 ]¹⁴C]In capsules⁶⁰Co activity, and does not suffer from high activity¹⁴Interference of beta decay of C. Measurement by the Cerenkov method relative to Gamma Spectroscopy⁶⁰Absolute counting efficiency at Co is higher and background is lower, thus being more sensitive. If urea 2¹⁴C]Therein contain⁶⁰Co by measuring urea [ alpha ], [ alpha ] and [ alpha ], [ alpha ] and [ alpha ], [ alpha ] and [ alpha ] or [ alpha ], [ alpha ] by measuring¹⁴C]Cerenkov light signal in capsule solution⁶⁰And measuring the Co activity, and further calculating the purity of the radioactive nuclide.

However, urea [ 2 ]¹⁴C]After the capsules are dissolved in water, the solution appears dark yellow, which is severely reduced⁶⁰Cerenkov detection efficiency of Co. How to correct accurately⁶⁰The Cerenkov detection efficiency of Co becomes a critical step and the method must also be suitable for large sample measurements.

Disclosure of Invention

The present invention aims at providing one kind of urea¹⁴C]In capsules¹⁴C radioactive nuclear purity analysis method based on TDCR Cerenkov technology⁶⁰Accurate analysis of urea [ 2 ] with simple operation on the basis of Cerenkov detection efficiency of Co¹⁴C]In capsules¹⁴Radionuclide purity of C.

To achieve this object, in a basic embodiment, the present invention provides urea [ 2 ]¹⁴C]In capsules¹⁴The method for analyzing the purity of the C radionuclide, which is based on TDCR Cerenkov measurement technology, comprises the following steps:

(1) obtaining a fitting relation curve: adding different amounts of yellow pigment solutions into different liquid flash bottles, respectively adding HCl solutions, uniformly mixing to obtain different simulation samples (pigment concentration range is 0-90 mg/L), measuring blank Cerenkov counts of different simulation samples by using a liquid flash instrument, and respectively adding a certain amount of yellow pigment solutions into each simulation sample⁶⁰Co, Cerenkov gauge measuring different simulated samples again with a liquid scintillation meterCounting, and calculating for each of the simulated samples⁶⁰Co detection efficiency, TDCR value, obtaining fitting on the basis⁶⁰Cerenkov detection efficiency epsilon of Co versus net TDCR value;

(2) sample measurement: taking urea¹⁴C]Dissolving in water to obtain a sample, measuring with a liquid scintillation meter, and calculating¹⁴C, measuring Cerenkov count of the actually measured sample by using a liquid scintillation meter, obtaining the detection efficiency of the actually measured sample through the fitting relation curve obtained in the step (1), and further calculating the activity concentration of the actually measured sample⁶⁰Activity concentration of Co;

(3) and (4) calculating a result: in the measured sample obtained in the step (2)¹⁴Activity concentration of C and⁶⁰calculating the activity concentration of Co to obtain urea¹⁴C]In capsules¹⁴Radionuclide purity of C.

According to the requirements of United states pharmacopoeia, urea must be accurately measured respectively¹⁴C]In capsules¹⁴C and impurity nuclide activity.¹⁴The C liquid flash measurement technology is mature, and the conventional commercial liquid flash technology device can measure¹⁴And C activity. As is conventional⁶⁰The Co measurement technology adopts a gamma spectrometer for measurement, and compared with the Cerenkov measurement technology, the technology⁶⁰The Co detection efficiency is low, the efficiency correction is complicated, and the preparation degree is not high.

TDCR is an absolute measurement technique, can not rely on outside mark source automatic correction liquid to dodge and survey efficiency, simplifies efficiency correction step greatly, and the wide application is surveyed the field in the liquid dodges. The application of TDCR techniques to Cerenkov measurements will greatly simplify the Cerenkov detection efficiency correction procedure. TDCR Cerenkov measurement technique has been widely used for high energy beta nuclides (⁹⁰Sr/⁹⁰Y、³²P) field of measurement. The invention creatively introduces the TDCR Cerenkov technology into urea [ 2 ]¹⁴C]In the capsule radioactive nuclear purity test, the TDCR liquid flash counter is used to accurately measure urea¹⁴C]In capsules¹⁴C radioactivity, and corrected using TDCR technique⁶⁰Cerenkov detection efficiency of Co. First, a series of different quenching degrees are prepared⁶⁰Co standard source samples, calculating TDCR values of the samples and⁶⁰cerenkov probing of CoEfficiency, and then fitting⁶⁰The relation curve of the Cerenkov detection efficiency of Co and the TDCR value is established⁶⁰TDCR Cerenkov efficiency correction curve for Co; when the sample is measured, the TDCR value of the sample is measured to complete the measurement of urea [ 2 ]¹⁴C]In capsule solution⁶⁰Cerenkov efficiency correction of Co, calculate Urea [ 2 ]¹⁴C]In capsule solution⁶⁰Activity of Co, and further, urea [ 2 ]¹⁴C]In capsules¹⁴C radionuclide purity.

In a preferred embodiment, the present invention provides urea [ sic ], [ solution of a mixture of two or more of the above¹⁴C]In capsules¹⁴C, in the step (1), the yellow pigment solution is a lemon yellow solution.

In a preferred embodiment, the present invention provides urea [ sic ], [ solution of a mixture of two or more of the above¹⁴C]In capsules¹⁴C, the radionuclide purity analysis method, wherein in the step (1), each ml of the model sample is added⁶⁰The amount of Co is 5.0-50 Bq.

In a preferred embodiment, the present invention provides urea [ sic ], [ solution of a mixture of two or more of the above¹⁴C]In capsules¹⁴C, wherein in the step (1), the purity of the radionuclide⁶⁰The Co detection efficiency is calculated by the formula:

wherein:

ε^60Cois composed of⁶⁰Co detection efficiency;

Dbl_sis composed of⁶⁰Double counting of the Co samples;

Dbl_bdouble counting for blank samples;

t is the measurement time of the sample;

A₀is composed of⁶⁰Theoretical value of Co activity.

In a preferred embodiment, the present invention provides urea [ sic ], [ solution of a mixture of two or more of the above¹⁴C]In capsules¹⁴C, wherein in the step (1), the TDCR value is calculated according to the formulaComprises the following steps:

wherein:

TDCR_netis the net TDCR value;

Dbl_sand Tpl_sDouble and triple counts of the sample;

Dbl_band Tpl_bDouble and triple counts of blank samples.

In a preferred embodiment, the present invention provides urea [ sic ], [ solution of a mixture of two or more of the above¹⁴C]In capsules¹⁴The method for analyzing the purity of a radionuclide of C, wherein in the step (3), urea [ 2 ]¹⁴C]In capsules¹⁴The calculation formula of the radionuclide purity of C is as follows:

in a preferred embodiment, the present invention provides urea [ sic ], [ solution of a mixture of two or more of the above¹⁴C]In capsules¹⁴C, wherein the flash apparatus is a Hidex300SL flash apparatus.

In a preferred embodiment, the present invention provides urea [ sic ], [ solution of a mixture of two or more of the above¹⁴C]In capsules¹⁴C, wherein the time measured by the liquid scintillation counter is 20 to 60 minutes.

The invention has the beneficial effect that the urea of the invention is utilized¹⁴C]In capsules¹⁴The radioactive nuclear purity analysis method of C can be based on TDCR Cerenkov measurement technique and can be used for accurate correction⁶⁰Accurate analysis of urea [ 2 ] with simple operation on the basis of Cerenkov detection efficiency of Co¹⁴C]In capsules¹⁴Radionuclide purity of C.

Compared with the measurement of a gamma spectrometer, the method has the following 3 advantages:

1)⁶⁰the detection efficiency of Co is high and can reach 8% at most, and the background is low, thereby being beneficial toAvoiding high activity¹⁴C, bremsstrahlung interference, so that the detection sensitivity is superior to that of gamma spectrometer measurement, and the measurement time can be effectively reduced;

2) the influence of the sample (concentration, density and volume) on the detection efficiency can be automatically corrected, and the sample is simple to prepare;

3) the continuous measurement of samples can be realized, the samples do not need to be frequently replaced, and the method is very suitable for analyzing a large batch of samples.

Drawings

FIG. 1 is a drawing of⁶⁰Cerenkov spectrum of Co.

FIG. 2 shows the results obtained in example 1⁶⁰TDCR Cerenkov efficiency calibration curve for Co.

Detailed Description

The following description will further describe embodiments of the present invention with reference to the accompanying drawings.

Example 1:

(A)⁶⁰TDCR Cerenkov detection efficiency correction curve of Co

Measurement Using Hidex300SL liquid scintillation Meter⁶⁰The Cerenkov spectrum of the radioactive solution sample of Co is shown in figure 1, the main distribution channel number of the spectrum is 20-350, and the counting of the part is selected in the actual measurement to calculate⁶⁰The activity of Co.

Fitting⁶⁰TDCR Cerenkov detection efficiency correction curve step of Co:

(1) adding different amounts of lemon yellow solution into different 20ml PE liquid flash bottles;

(2) respectively adding 0.1M HCl solution to the total volume of 20ml of the sample, and uniformly mixing (the pigment concentration ranges from 0mg/L to 90 mg/L);

(3) measuring blank counts of each simulated sample by using a Hidex300SL liquid scintillation spectrometer, wherein the measurement time is 20 minutes;

(4) adding 100Bq to each of the simulated samples⁶⁰Co (accurately weighed to obtain⁶⁰Exact activity of Co), high quenching degree of the simulated sample added to 130Bq⁶⁰Co (accurately weighed to obtain⁶⁰The exact activity of Co);

(5) measuring each simulated sample for the second time by using a Hidex300SL liquid scintillation meter, wherein the measuring time is 20 minutes;

(6) calculating for each simulated sample according to equation (1)⁶⁰Co detection efficiency;

wherein:

ε^60Cois composed of⁶⁰The detection efficiency of Co;

Dbl_sis composed of⁶⁰Double counting of the Co samples;

Dbl_bdouble counting for blank samples;

t is the measurement time of the sample, s;

A₀is composed of⁶⁰Theoretical value of Co activity.

(7) Calculating the net TDCR value for each simulated sample according to equation (2);

wherein:

TDCR_netis the net TDCR value;

Dbl_sand Tpl_sDouble and triple counts of the sample;

Dbl_band Tpl_bDouble and triple counts of blank samples.

(8) Fitting⁶⁰Cerenkov detection efficiency of Co versus net TDCR value.

As shown in FIG. 2, in a 20ml system⁶⁰The TDCR Cerenkov detection efficiency correction curve of Co is shown as formula (3), and has high correlation (R)²0.9875). The net TDCR value of the simulated sample obtained in the measurement is calculated by the formula (3)⁶⁰Co detection efficiency.

ε＝0.0566*ln(TDCR_net)+0.119 (3)

(II)¹⁴Purity analysis of C-radionuclides

Taking 1 or more granules of urea¹⁴C]The capsule (Shenzhen, produced by Daenhei Biotech Co., Ltd.) is prepared by dissolving with appropriate amount of water under slight heat, and then using TDCR liquid scintillation counting to accurately measure the content of the sample¹⁴C activity concentration, and measuring the activity concentration in the sample to be measured by Cerenkov counting⁶⁰Activity concentration of Co; estimating in a sample¹⁴The purity of C radionuclide should not be less than 99.9%.

1. In a sample⁶⁰Activity analysis of Co (and other high energy beta-gamma nuclides)

(1) Mixing one particle of¹⁴C]Transferring the capsule and 3ml deionized water to a 7ml flash bottle, heating to 60 deg.C, and preparing urea¹⁴C]Capsule sample fluid (containing about 2.78E +04 Bq)¹⁴C)；

(2) Transferring 0.5ml of urea [ solution ]¹⁴C]Capsule sample fluid (of about 4.63E +03 Bq)¹⁴C) To 20ml PE liquid flash bottle; accurately weighing to obtain the urea [ 2 ]¹⁴C]Capsule sample liquid quality;

(3) adding ultrapure water to dilute the sample until the total weight is 20g, and uniformly mixing;

(4)20g of ultrapure water as a blank sample;

(5) cerenkov counts of the samples were measured using Hidex300SL for 20 minutes;

(6) calculating the detection efficiency of the sample according to the formula (3) so as to calculate the content of the sample⁶⁰Activity of Co;

(7) if the sample count is close to the background value, then urea is estimated according to the formula (4)¹⁴C]In capsule sample⁶⁰The upper limit of activity concentration of Co (and other high energy beta-gamma species).

Wherein:

k ═ 1.645 (i.e., 95% confidence level);

b is blank sample counting of the analysis process;

t is the detection time of the sample;

epsilon is the detection efficiency of nuclides;

r is the chemical recovery rate of the analysis process;

f is the percentage of the final measured sample to the total sample volume;

w is the sample mass, g.

The experiment does not relate to a chemical separation process, and R and f are both 100 percent; 0.5ml of urea [ sic ], [ solution ]¹⁴C]In diluted samples of capsule sample liquid⁶⁰The detection efficiency ε of Co was 7.6. + -. 0.4%.

2. In a sample¹⁴Liquid flash measurement of C activity

(1) Transferring 0.1ml of urea [ solution ]¹⁴C]Capsule sample fluid (about 930 Bq)¹⁴C) To 7ml PE liquid flash bottle; accurately weighing urea [ 2 ]¹⁴C]Capsule sample liquid quality;

(2) adding 6.9ml of scintillation liquid, and uniformly mixing to obtain the urea solution¹⁴C]A capsule sample;

(3) the blank sample preparation is that 0.1ml of ultrapure water and 6.9ml of scintillation fluid are mixed evenly;

(4) measuring the sample by using a Hidex300SL TDCR liquid scintillation meter for 5 minutes; calculating in the sample¹⁴Activity concentration of C;

(5) calculating urea [ 2 ] according to the formula (5)¹⁴C]In capsule¹⁴C]The lower limit of radionuclide purity of (c).

(III) example verification

1. Preparation of urea¹⁴C]Capsule solution

Mixing a granule of urea¹⁴C]Transferring the capsule and 3ml deionized water to a 7ml flash bottle, heating to 60 deg.C, and preparing urea¹⁴C]Capsule sample fluid (containing about 2.78E +04 Bq)¹⁴C) Sample number¹⁴C-S0, see Table 1.

TABLE 1 Urea [ 2 ]¹⁴C]Capsule sample liquid

2、⁶⁰Co Activity measurement

According to the above section, 0.5ml of urea [ alpha ], [ alpha ] was measured¹⁴C]In capsule sample liquid⁶⁰Co activity, results are shown in Table 2.

TABLE 20.5 mL of urea [ 2 ]¹⁴C]In capsule diluent⁶⁰Measurement results of Co

3. Urea [ 2 ]¹⁴C]Purity of capsule radionuclide

According to the above section, urea is calculated¹⁴C]In capsule sample liquid¹⁴C activity concentration, and calculating urea [ 2 ] according to the formula (5)¹⁴C]In capsules¹⁴The activity concentration of C, the calculation result of which is shown in Table 3, satisfies the requirement of Urea [, ]¹⁴C]In capsules¹⁴The purity of C radioactive nucleus is more than 99.9%.

TABLE 3 Urea [ 2 ]¹⁴C]Purity of capsule radionuclide

It will be apparent to those skilled in the art that various changes and modifications may be made in the present invention without departing from the spirit and scope of the invention. Thus, if such modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is intended to include such modifications and variations. The foregoing examples or embodiments are merely illustrative of the present invention, which may be embodied in other specific forms or in other specific forms without departing from the spirit or essential characteristics thereof. The described embodiments are, therefore, to be considered in all respects as illustrative and not restrictive. The scope of the invention should be indicated by the appended claims, and any changes that are equivalent to the intent and scope of the claims should be construed to be included therein.