CN1696641A - Verification sample of liquid ability containing niacinamide, and preparation method - Google Patents

Abstract

An ability verification sample of liquid containing niacinamide is composed of 4 - 9 liquid samples as their concentration being presented in equal ratio relation. The equal ratio coefficient between liquid samples is 0.60 - 0.95 and samples solvent is 0.9 % sodium chloride - normal saline. The method for preparing the samples is also disclosed.

Description

The verification sample of liquid ability and the preparation method that contain niacinamide

Technical field

The present invention relates to toxicology proficiency testing technical field, particularly contain single food additive component verification sample of liquid ability, and the preparation method of this sample.

Background technology

Niacinamide is a nicotinic acid: promote the health of digestive system, alleviate gastrointestinal disorders; Promote skin health; Prevention is eased up and is separated serious antimigraine; Stimulate circulation, blood pressure is reduced; The alleviating diarrhoea phenomenon; Alleviate the uncomfortable disease of Meniere's syndrome; Make people's physical efficiency make full use of food and increase energy; Treatment oral cavity, lip inflammation prevent halitosis; Reduce cholesterol and triglyceride.So be widely used aspect medicine, feed and the health food because of it has above-mentioned multiple efficacies, but some crowd has bad reaction, as dizzy, feel sick, epigastric discomfort etc., and human body takes in that niacinamide is excessive to have harmful effect to health every day, as causing nephrocyte poisoning etc.Therefore must test to the toxicity and the content of niacinamide in various product of niacinamide, whether accuracy depends on breadboard detectability to testing result.

Ability verification is to estimate one of the important means of lab investigation ability of participating in the experiment between the laboratory, and it then is the precondition that guarantees proficiency testing plan smooth implementation that the organizer offers the breadboard specimen of respectively participating in the experiment.The proficiency testing sample is different from general lab investigation sample, and it must possess homogeneity and stability features, also should satisfy the requirement of statistical appraisal simultaneously.Data is looked into newly and shown: the specimen that is used for ability verification between the toxicological experiment chamber is not appeared in the newspapers both at home and abroad as yet.

Summary of the invention

The objective of the invention is to replenish ability verification blank between the toxicological experiment chamber, a kind of verification sample of liquid ability that contains niacinamide is provided, sample homogeneity, stability and statistical appraisal meet the proficiency testing requirement, the preparation method of this sample also is provided in addition, and method is simple and guarantee properties of sample and be prepared into power.

The technical scheme that the present invention is adopted for achieving the above object is: the verification sample of liquid ability that contains niacinamide, comprise that 4～9 concentration are the fluid sample of geometric ratio relation, geometric ratio coefficient between each sample is 0.60～0.95, and the solvent of sample is 0.9% sodium chloride physiological saline.

Described sample is divided into 7 samples, and the geometric ratio coefficient between each sample is 0.9.Each sample concentration is respectively: No. 1 liquid-177.78mg/mL; No. 2 liquid-160.00mg/mL; No. 3 liquid-144.00mg/mL; No. 4 liquid-129.60mg/mL; No. 5 liquid-116.64mg/mL; No. 6 liquid-104.98mg/mL; No. 7 liquid: 94.48mg/mL.

The described verification sample of liquid ability that contains niacinamide,

The preparation method who contains the verification sample of liquid ability of niacinamide of the present invention is:

1. at first according to zoopery, determine the maximum concentration and the least concentration of this group sample.

2. again according to amount that zoopery presented. effect relationship determines that this group sample should be divided into the geometric ratio coefficient between what samples and each sample, adopts " low than dilution method " obtain solution.

2.1. take by weighing the pure powder of a certain amount of medicinal niacinamide, add 0.9% sodium chloride physiological saline of a constant volume, mix the back constant volume, mixing again, this solution is No. 1 liquid.

2.2. from No. 1 liquid, take out and a certain amount ofly carry out aseptic subpackagedly, in former volumetric flask, add 0.9% sodium chloride physiological saline of same amount simultaneously, mix the back constant volume, mixing again, this solution is liquid No. 2.

2.3. repeat 2.2 the operation, join successively No. 3 liquid, No. 4 liquid, No. 5 liquid, No. 6 liquid, No. 7 liquid.

2.4. packaged sample is carried out homogeneity, stability test, qualified getting final product.

The invention has the beneficial effects as follows: proficiency testing sample of the present invention, its stability, uniformity meets the proficiency testing requirement, and can carry out statistical appraisal.Sample in addition uniqueness indicates, and the random sampling granting, and the behavior of ganging up between the laboratory of can effectively preventing to participate in the experiment makes test result more credible.Proficiency testing sample of the present invention has extensive applicability, it is not only applicable to the ability verification of toxicological experiment chamber, also be widely used in the industry-by-industry testing staff's relevant horizontal checkout and breadboard quality control, for example: the foodsafety inspection and quarantine department with foodsafety; Food additives are produced and use department; Food processing department etc.The present invention has finished the preparation of proficiency testing sample between the toxicological experiment chamber first, has filled up the blank in this field, first " compound method of drug solution-low than dilution method " in the pharmacological experiment method is applied in the proficiency testing sample preparation technology simultaneously.

Embodiment

The present invention is described in more detail below in conjunction with embodiment.

Embodiment 1:

Preparation 100mL contains the verification sample of liquid ability of niacinamide

According to the character of food additives-niacinamide and the solvent of this proficiency testing fluid sample of toxicological experiment requirement selection preparation is 0.9% sodium chloride physiological saline.

1. at first according to zoopery, the maximum concentration of determining this group sample is 177.78mg/mL, and least concentration is 94.48mg/mL.

2. determine that according to the amount-result relation that zoopery presented this group sample is divided into 7 samples again, the geometric ratio coefficient between each sample is 0.9, by each sample of geometric ratio relation preparation, and concrete employing the " low " obtain solution than dilution method:

2.1 take by weighing the pure powder of the medicinal niacinamide of 177.78g, add the 0.9% sodium chloride physiological saline of 1000mL, mix the back constant volume, mixing again, this solution is No. 1 liquid.

Carry out aseptic subpackagedly 2.2 from No. 1 liquid, take out 100mL, in former volumetric flask, add 100mL0.9% sodium chloride physiological saline simultaneously, mix the back constant volume, mixing again, this solution is liquid No. 2.

2.3 repeat 2.2 the operation, join successively No. 3 liquid, No. 4 liquid, No. 5 liquid, No. 6 liquid, No. 7 liquid.Each sample concentration is respectively: No. 1 liquid-177.78mg/mL; No. 2 liquid-160.00mg/mL; No. 3 liquid-144.00mg/mL; No. 4 liquid-129.60mg/mL; No. 5 liquid-116.64mg/mL; No. 6 liquid-104.98mg/mL; No. 7 liquid: 94.48mg/mL.

2.4 with packaged sample, check through double through being up to the standards, registration, and in addition uniqueness indicates.The sample of randomly drawing some carries out homogeneity, and stability test qualifiedly can be provided sample to the laboratory of participating in the experiment.

Prepared properties of sample is tested:

28 samples of picked at random are used for homogeneity and stability is checked respectively from pack each the dosage sample with seals, choose 196 in sample altogether, make selected sample have the representativeness of height.

1 uniformity test:

10 samples of picked at random carry out the homogeneity inspection respectively from packaged each dosage sample.Each sample is divided into two parts of test portions, and all test portions promptly use identical method of testing and instrument test within a short period of time by identical personnel with the absorbance A of random order under test 261nm under the repeated condition in same laboratory.Log10 dose by absorbance conversion sample.Absorbance test result and corresponding log10 dose value see Table 1.

For each dosage, the log10 dose of sample is $\log D=\log (\frac{A}{430\×6.5\×{10}^{-6}}\×\frac{0.2}{10}),$

A is an absorbance in the formula;

Sample log10 dose mean value is $\stackrel{\‾}{{\log D}_x}=({\log D}_{x1}+{\log D}_{x2})/2;$

The log10 dose extreme difference is w between test portion _x=| logD _X1-logD _X2|;

The log10 dose population mean is $\stackrel{\‾}{\stackrel{\‾}{\log D_x}}=\∑\stackrel{\‾}{\log D_x}/g$ , g is the sample number of choosing in the uniformity test:

The standard deviation of log10 dose population mean is $s_x=\sqrt{\∑{(\stackrel{\‾}{\log D_{\mathrm{xt}}}-\stackrel{\‾}{\stackrel{\‾}{\log D_x}})}^2/(g-1)};$

The log10 dose standard deviation is in the sample $s_w=\sqrt{\mathrm{\Σ}{w}_x^2/2g};$

Sample room log10 dose standard deviation is $s_s=\sqrt{s_x^2-s_w^2/2}.$

Table 1 sample log10 dose value and Evaluation for Uniformity

Table C1 sample log10 dose value and Evaluation for Uniformity (continuing)

Use overall probit-log10 dose figure that the fatal rate recurrence of each dosage sample of laboratory report is converted into the log10 dose value, and obtain the standard deviation S D of these log10 dose values respectively _i(also listing in table 1).

Result from table 1 as can be known, for the sample of each dosage, sample room log10 dose standard deviation s _sBe far smaller than by the convert standard deviation S D of the log10 dose value that obtains of the fatal rate of this dosage sample _i0.3 times.This mobility that shows sample room can be ignored in statistical study of carrying out subsequently and merit rating, that is to say that sample is uniform.

2 stability tests:

18 samples of picked at random are used for stability test respectively from packaged each dosage sample.These samples were placed at room temperature (18～25 ℃) 5 days, were placed on then in 40 ℃ of insulation cans 5 days, placed room temperature more following 20 days again.On uniformity test same day, stability test carries out respectively for behind the uniformity test the 10th day and the 20th day.Each stability test is chosen 6 samples respectively from 18 samples of each dosage, wherein 3 samples are used for the absorbance test, and 3 samples are used for zoopery.

In the test of sample absorbance, each sample is divided into 2 parts of test portions, adopts identical personnel, instrument, method of testing and the laboratory of uniformity test to test.Log10 dose value by absorbance test result and conversion sees Table 2, and the absolute difference of the log10 dose result of sample and the log10 dose population mean in the uniformity test is calculated by following formula in the stability test:

To each dosage, sample log10 dose average $\stackrel{\‾}{\log D_y}=(\log D_{y1}+\log D_{y2})/2;$

Total log10 dose mean value $\stackrel{\‾}{\stackrel{\‾}{\log D_y}}=\∑\stackrel{\‾}{\log D_y}/h$ , h is the sample number of choosing in the stability test;

Absolute difference between homogeneity and the stability test log10 dose result $d=|\stackrel{\‾}{\stackrel{\‾}{\log D_y}}-\stackrel{\‾}{\stackrel{\‾}{\log D_x}}|.$

To each dosage, this absolute difference is far smaller than by the convert standard deviation S D of the log10 dose value that obtains of the fatal rate of this dosage sample _i0.3 times.This shows suspiciously in statistical study of carrying out subsequently and merit rating ignores the sample influence that variation brought under these conditions.

The evaluation of table 2 sample log10 dose value stabilization

Simultaneously, adopt 3 series of samples to carry out zoopery, and adopt improved Bliss method to calculate logarithm median lethal dose (logLD ₅₀), mouse death rate result and logLD that each sample caused ₅₀Result of calculation is listed in table 3.If d _aBe the 10th day and the 20th day measured logLD ₅₀Value and uniformity test measured logLD on the same day ₅₀The absolute difference of value, this difference is less than merit rating 0.3 times with sane standard deviation NIQR.Show that sample in time and go through the variation of condition and influence that the mobility that produces is produced the zoopery result can be ignored equally in subsequently statistical study and merit rating.

Table 3 logarithm median lethal dose estimation of stability

??logD	The 0th day				The 10th day				The 20th day
													??1	??2	??3	On average	??1	??2	??3	On average	??1	??2	??3	On average
	??3.5509	??100％	??100％	??100％	??100％	??100％	??10％	??100％	??100％	??100％	??100％	??100％													??100％
??3.5051													??90％	??80％	??80％	??83.3％	??80％	??80％	??80％	??80％	??80％	??80％	??90％	??83.3％
	??3.4594	??40％	??60％	??50％	??50％	??50％	??60％	??60％	??56.7％	??50％	??50％	??50％													??50％
??3.4136													??30％	??30％	??20％	??26.7％	??30％	??40％	??40％	??36.7％	??30％	??40％	??20％	??30％
	??3.3679	??10％	??10％	??10％	??10％	??20％	??10％	??10％	??13.3％	??10％	??20％	??10％													??13.3％
??3.3221													??10％	??10％	??10％	??10％	??10％	??0％	??0％	??3.3％	??10％	??0％	??0％	??3.3％
	??3.2764	??0％	??0％	??0％	??0％	??0％	??0％	??0％	??0％	??0％	??0％	??0％													??0％
?LogLD 50													??3.444	??3.440	??3.449	??3.444	??3.440	??3.442	??3.442	??3.441	??3.445	??3.441	??3.449	??3.445
	??da					??0.004	??0.002	??0.002	??0.003	??0.001	??0.003	??0.005													??0.001
??NIQR													??0.034	??0.034	??0.034	??0.032	??0.034	??0.034	??0.034	??0.032

Be that absorbance test experiments or zoopery result have illustrated that sample is sufficiently stable.

Claims (4)

1, contain the verification sample of liquid ability of niacinamide, it is characterized in that: sample is divided into 4～9 geometric ratios and concerns sample, and the geometric ratio coefficient between each sample is 0.6～0.95, and the solvent of sample is 0.9% sodium chloride physiological saline.

2, the verification sample of liquid ability that contains niacinamide according to claim 1 is characterized in that: sample is divided into 7 samples, and the geometric ratio coefficient between each sample is 0.9.

3, the verification sample of liquid ability that contains niacinamide according to claim 1 is characterized in that: sample is divided into 7 samples, and each sample concentration is respectively: No. 1 liquid-177.78mg/mL; No. 2 liquid-160.00mg/mL; No. 3 liquid-144.00mg/mL; No. 4 liquid-129.60mg/mL; No. 5 liquid-116.64mg/mL; No. 6 liquid-104.98mg/mL; No. 7 liquid: 94.48mg/mL.

4, according to claim 1, the 2 or 3 described preparation methods that contain the verification sample of liquid ability of niacinamide be:

(1), determines the maximum concentration and the least concentration of this group sample according to zoopery;

(2) determine that according to the amount-result relation that zoopery presented this group sample should be divided into the geometric ratio coefficient between what samples and each sample again, adopt " low " obtain solution than dilution method:

2.1 take by weighing the pure powder of a certain amount of medicinal niacinamide, add 0.9% sodium chloride physiological saline of a constant volume, mix the back constant volume, mixing again, this solution is No. 1 liquid;

2.2 from No. 1 liquid, take out and a certain amount ofly carry out aseptic subpackagedly, in former volumetric flask, add 0.9% sodium chloride physiological saline of same amount simultaneously, mix the back constant volume, mixing again, this solution is liquid No. 2;

2.3 repeat 2.2 the operation, join successively No. 3 liquid, No. 4 liquid, No. 5 liquid, No. 6 liquid, No. 7 liquid;

2.4 packaged sample is carried out homogeneity, stability test, qualified getting final product.