葫芦巴碱标准物质的研制

研制葫芦巴碱标准物质。分别采用质量平衡法和定量核磁法两种不同原理方法对葫芦巴碱标准物质的纯度进行定值。利用高效液相色谱法对葫芦巴碱标准物质的均匀性和稳定性进行考察。对葫芦巴碱标准物质纯度定值结果的不确定度进行评定。结果表明,葫芦巴碱标准物质的纯度定值结果为99.31%,扩展不确定度为0.4%(k=2)。研制的葫芦巴碱标准物质量值准确,均匀性和稳定性符合二级标准物质技术要求。     

黄豆黄素纯度标准物质研制

建立黄豆黄素纯度标准物质的研制方法。选择纯度大于98%（质量分数）的黄豆黄素标准品作为标准物质候选物,通过加热和冷冻干燥去除多余的水分。通过红外、质谱、核磁氢谱进行结构确证和表征后分装,采用质量平衡法进行均匀性和稳定性检验。结果显示,标准物质均匀性良好,在常温条件下保存12个月稳定;采用质量平衡法和定量核磁法进行纯度定值,质量平衡法的定值结果为99.09%,定量核磁法的定值结果为99.13%,取平均值99.1%作为最终定值结果;对定值、均匀性和稳定性引入的不确定度进行了系统评定,扩展不确定度为0.3%(k=2)。研制的黄豆黄素纯度标准物质已申报国家一级标准物质,编号为GBW 10171。该标准物质可用于食品、保健品、饲料中黄豆黄素含量检测。     

没食子酸丙酯纯度标准物质的研究

研制了没食子酸丙酯纯度标准物质。依据国家《一级标准物质研制技术规范》,采用高效液相色谱(HPLC)法和差示扫描量热(DSC)法对没食子酸丙酯纯度标准物质进行联合定值,进行了相应的不确定度评定。研制的没食子酸丙酯纯度标准物质定值结果为(99.8±0.5)%(k=2,P=0.95)。该标准物质可用于相关药品生产及使用单位的质量控制和分析方法确认评价。     

诱惑红溶液标准物质的研制及不确定度评定

建立了食用合成色素诱惑红溶液标准物质的制备和定值方法,研制了100 mg/L的诱惑红溶液标准物质。采用制备液相色谱对筛选的市售原料纯化,得到纯度大于99%的诱惑红纯品;通过核磁共振(1H NMR谱)和液相色谱-质谱(HPLC-LTQ/MS)准确定性分析后,利用高效液相色谱法(HPLC)对诱惑红纯物质进行纯度定值。以0.1 mol/L乙酸铵和甲醇为流动相进行等度洗脱,采用Intersil ODS-C18(250 mm×4.6 mm,5μm)进行分离,检测波长240 nm。为保证纯度测量的准确性,采用多家联合定值对诱惑红的纯度进行定值,诱惑红纯物质的定值纯度为99.61%(λ=240 nm)。诱惑红溶液标准物质经重量-容量法配制后,进行均匀性和稳定性实验,浓度赋值后进行不确定度评定,诱惑红溶液的量值为100 mg/L,扩展相对不确定度为1.0%(k=2)。该溶液标准物质已批准为国家级标准物质,可为相关部门提供检测标准。     

NTO纯度标准物质定值研究

为了对纯度标准物质3-硝基-1,2,4-三唑-5-酮(NTO)定值,获得其纯度值和不确定度,采用"杂质扣除法"对标准物质进行定值,用化学分析法对定值结果进行验证.通过对定值过程的A、B类不确定度评定,获得定值结果的不确定度.NTO纯度标准物质的纯度值为99.57%,扩展不确定度U=0.02%(k=2).     

辛基二茂铁同分异构体标准物质的制备

以辛基二茂铁为原材料,利用常压色谱柱结合环糊精包结分离制得(2-辛基)-二茂铁、(3-辛基)-二茂铁、(4-辛基)-二茂铁3种相对纯度均大于99.5%的辛基二茂铁同分异构体,作为标准物质候选物。利用气相色谱法检测,考察标准物质候选物的均匀性和稳定性,用气相色谱–质谱法、核磁共振法分析候选物中杂质的结构,确定其类型。用内标法和主成分自身对照法对不同的杂质进行定值,并对定值不确定度进行评定。(2-辛基)-二茂铁、(3-辛基)-二茂铁、(4-辛基)-二茂铁的纯度分别为99.5%,99.5%,99.8%,扩展不确定度均为0.2%(k=2)。该标准物质可为相关物质的检测提供量值溯源标准。     

黄芩素纯度标准物质的定值及其不确定度评定

为了满足食品及医药等领域的检测需求,研制了黄芩素纯度标准物质。采用液相色谱–质谱法和红外光谱法对黄芩素纯度标准物质原料定性后,利用高效液相色谱法(HPLC)和定量核磁技术(Quantitative Nuclear Magnetic Resonance Spectroscopy,QNMR)对黄芩素的纯度进行了定值,并用HPLC法对黄芩素纯度标准物质进行了均匀性检验和稳定性考察。对定值结果的不确定度进行了评价,研制的黄芩素纯度标准物质的定值结果和扩展不确定度分别为98.8%,0.8%(k=2)。     

加替沙星纯度标准物质研制

研制加替沙星纯度标准物质。采用质量平衡法和氢谱定量核磁法对加替沙星纯度标准物质候选物进行纯度定值,采用卡尔费休法和热重分析法准确测量了影响主成分纯度的水分含量,并考察了水分含量的稳定性。开展了加替沙星纯度定值、均匀性检验、稳定性考察以及不确定度评估。结果表明,加替沙星纯度标准物质的纯度值为93.1%,扩展不确定度为0.6%(k=2),水分含量为6.6%,特性量值均匀性良好,6个月稳定性可靠,被认定为国家二级标准物质,编号为GBW(E) 100476。研制的加替沙星纯度标准物质填补了国内空白,同时也为吸湿性较强的药物纯度标准物质研制过程中水分测定提供了参考与借鉴。     

甲醇中丙烯酸乙酯溶液标准物质制备

研制特征量值为1 000μg/mL甲醇中丙烯酸乙酯溶液标准物质。分别利用气相色谱-质谱联用法、核磁共振波谱法和红外光谱法对丙烯酸乙酯标准品原料进行定性确认。采用质量平衡法对主成分含量进行量值核验，丙烯酸乙酯标准品纯度（质量分数）为99.842%，扩展不确定度为0.3%，量值在证书给出的不确定度范围内，因此采用证书标识量值作为原料标准值，证书中标识的不确定度作为原料不确定度。以丙烯酸乙酯标准品为原料，采用重量-容量法制备溶液标准物质，分别采用F检验和t检验对标准物质进行均匀性和稳定性检验，并对其定值结果的不确定度进行评定。结果表明，该标准物质均匀性和稳定性良好，有效期为12月，定值结果的相对扩展不确定度为2%(k=2)，可用于环境样品中丙烯酸乙酯分析方法的确认和评价以及仪器校准与检测质量控制。     

诺龙甲醇溶液标准物质的研制

利用色-质联用法和红外光谱法对诺龙纯品原料定性后,采用高效液相色谱多家定值方法对诺龙纯度进行定值,经重量法配制,制得了诺龙甲醇溶液标准物质,并对制备的溶液标准物质进行均匀性和稳定性检验.对定值不确定度进行了评定,当诺龙甲醇溶液标准物质的浓度为1.00 mg/mL时,相对扩展不确定度为1.0%,k=2.     

A new traceability scheme for the development of international system-traceable persistent organic pollutant reference materials by quantitative nuclear magnetic resonance

Quantitative nuclear magnetic resonance (qNMR) was used for the purity determination of neat compounds of persistent organic pollutants (POPs). qNMR is a unique quantitative method that is not only traceable to the International System of Units (SI), but it also does not require a standard of its own. The purities of the POP compounds determined in this work were traceable to a single certified reference material (CRM), which is extremely attractive for reference material producers. The purities observed by qNMR were equivalent to those observed by gas chromatography with flame ionization detection (GC/FID) or a differential scanning calorimetry (DSC) combined with a thermogravimetric analyzer (TGA). The uncertainties obtained by the qNMR method were comparable to being slightly larger than those observed by DSC.     

A comparative uncertainty study of the calibration of macrolide antibiotic reference standards using quantitative nuclear magnetic resonance and mass balance methods

This study introduces the general method of quantitative nuclear magnetic resonance (qNMR) for the calibration of reference standards of macrolide antibiotics. Several qNMR experimental conditions were optimized including delay, which is an important parameter of quantification. Three kinds of macrolide antibiotics were used to validate the accuracy of the qNMR method by comparison with the results obtained by the high performance liquid chromatography (HPLC) method. The purities of five common reference standards of macrolide antibiotics were measured by the ¹H qNMR method and the mass balance method, respectively. The analysis results of the two methods were compared. The qNMR is quick and simple to use. In a new medicine research and development process, qNMR provides a new and reliable method for purity analysis of the reference standard.     

藏药诃子质量标志物诃子酸的分离分析及标准化研究

依据GB/T 15000—2008《标准样品工作导则》的要求,研制诃子酸国家标准样品.以诃子的干燥成熟果实为原料,采用大孔吸附树脂、制备型高效液相色谱技术对标准样品进行制备,经过纯度分析、结构鉴定、均匀性检验、稳定性检验,最后进行联合定值.基于高效液相色谱(HPLC)技术,采用不同检测波长进行纯度测试,样品纯度均大于98%.基于液相-质谱(LC-MS)进行纯度分析,未发现明显杂质峰.通过紫外光谱(UV)、红外光谱(IR)、质谱(MS)、核磁共振(NMR)等技术确定其结构为诃子酸.样品均匀性良好,4℃条件下24个月内稳定性良好.定值结果确定诃子酸纯度为98.08%,在95%置信区间范围内的相对扩展不确定度为0.50%.研制出的诃子酸(GSB 11-3725-2020)国家标准样品可用于含量测定、检测方法评定、相关产品的检测与质量控制.     

罗丹明B纯度标准物质的研制

以商购罗丹明B为原料,进行重结晶提纯,制备罗丹明B纯度标准物质。采用红外光谱(IR)、高分辨质谱和核磁共振谱(NMR)进行定性分析。样品分装400瓶后,依据国家《一级标准物质研制技术规范》,采用液相色谱-二极管阵列法对随机抽取的15瓶样品进行均匀性检验,经F检验表明,在95%的置信区间范围内,样品均匀性良好。在室温下,经过30个月稳定性考察,结果表明样品稳定性良好。标准物质经国内8家具有分析资质的实验室进行协同定值,定值结果为99.0%,扩展不确定度为1.0%(k=2)。该标准物质达到了国家标准物质的技术要求,可用于有关罗丹明B的分析方法校正和质量控制。     

High performance liquid chromatography - Quantitative nuclear magnetic resonance - High performance liquid chromatography for purity measurement of human insulin

Quantitative Nuclear Magnetic Resonance (qNMR) is a reliable quantitative spectroscopic technique, wherein the intensity of a resonance line is directly proportional to the number of resonant nucleus, and the absolute content of the compound can be determined, this means the inorganic stabilizer in the sample would not affect the result of qNMR. High performance liquid chromatography (HPLC) is a common analytical method with a high separation capacity. This study combined HPLC and qNMR, to measure the purity of Human Insulin (HI). It started from an original HI. The first step is purifying the original HI by HPLC to get a purified HI, with organic purity of 99.78%. The second step is assessing the absolute content of the purified HI by qNMR, and got 40.25%. The third step is measuring the purity of original HI by HPLC again, using the purified HI as the reference material. This method, called HPLC-qNMR-HPLC, is more accurate (84.12%?±?1.14%) than the traditional IDMS (isotope dilution mass spectrometry) method (86.6%?±?3.4%). This study expanded the application of qNMR to proteins with molecular weight of about 5800, and showed that this method can be widely used in measuring the purity of macromolecular proteins.     

Development of bovine serum albumin certified reference material

We present the development process for National Institute of Metrology (NIM) bovine serum albumin (BSA) certified reference material (CRM). Each CRM unit contains about 200 mg of purified BSA. The moisture, ignition residue, molecular weight, and high-performance liquid chromatography (HPLC) purity were analyzed and mass spectrometry based protein identification was carried out to ensure the material was BSA. Both amino acid based isotope dilution mass spectrometry (IDMS) and a purity deduction method were selected for value assignment. The certified value was the average of the IDMS and the purity deduction result. HPLC purity analysis was used to examine the homogeneity and stability of solid BSA CRM. Fifteen units were selected for between-bottle homogeneity examination and seven subsamples from the same bottle were selected for within-bottle homogeneity examination. Statistics showed the CRM passed both the between-bottle and the within-bottle homogeneity examination. The CRM stability under storage conditions (-20 °C) was tested for 18 months and no trend was observed. Uncertainties from the balance, amino acid purity, hydrolysis, method reproducibility, homogeneity, and stability were taken into account in uncertainty evaluation. The final certified value of NIM BSA CRM is (0.963±0.038) g/g.     

阿维菌素B1a纯物质的制备纯化研究

本研究致力于制备纯化出高纯阿维菌素B1a,为核磁定量及质量平衡法提供计量溯源纯物质,从而给阿维菌素标准物质(研制中)纯度定值时提供纯度参考标准。利用制备型液相色谱对阿维菌素原料(B1a含量为95.71%)进行纯化,除去痕量杂质,真空干燥及冷冻干燥后得到阿维菌素B1a高纯物质。建立了基于制备液相色谱-真空干燥的阿维菌素B1a高纯物质的制备纯化工艺:采用Agilent Prep HT XDB-C18型制备柱,流动相为水/甲醇(15∶85),进样量500μL,流速20.0m L/min。经超高效液相色谱(UPLC)检测,产品纯度达到99.74%,可以满足核磁定量及质量平衡法的要求,并利用液相色谱串联质谱以及核磁共振法对产品进行定性分析。     

茶碱标准物质的研制与定值

建立了茶碱标准物质的制备和定值方法.将市售茶碱原料纯化、干燥、混匀后.分装成500瓶样品.随机抽取其中11瓶做均匀性检验.经F检验和T检验.结果表明在95%置信范围内样品的均匀性良好;稳定性检验按短期稳定性(1月)和长期稳定性(12月)分别进行,长期稳定性结果通过了T检验,表明在20℃条件下茶碱的稳定期不少于12个月....