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.     

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。     

睾酮甲醇溶液标准物质的定值及不确定度评定

针对目前食品中兴奋剂类药物检测的需求,研制了睾酮甲醇溶液国家级标准物质。通过对经筛选的市售原料纯品进行液相色谱-质谱(LC-MS)和红外光谱(IR)定性分析后,利用高效液相色谱法(HPLC)对睾酮蛋白同化类固醇类兴奋剂原料进行纯度定值。利用HPLC在244nm监测,0.1%HAc-乙腈(50∶50,体积比)作为流动相进行等度洗脱,以Inertsil ODS-SP(250mm×4.6mm,5μm)进行分离,测得液相条件下睾酮固体的纯度为99.89%。为保证纯度测量的准确性,采用多家联合定值对睾酮的纯度进行检验。睾酮溶液标准物质经重量-重量法配制后,进行均匀性和稳定性实验,浓度赋值后进行不确定度评定。研制的睾酮溶液标准物质目前已被批准为国家二级标准物质并应用于实际检测。     

2,4,6-三氯酚纯品原料纯度定值方法研究

对用于溶液标准物质制备的纯品原料2,4,6-三氯酚纯度定值方法进行了探讨。采用气相色谱质谱法(GC–MS)对主成分和杂质进行定性鉴定。用高效液相色谱法(HPLC–DAD)、气相色谱法(GC–FID)和差示扫描量热法(DSC)3种不同原理的方法对主成分定值。卡尔费休法测量水分,电感耦合等离子体质谱(ICP–MS)测量无机杂质。2,4,6-三氯酚纯度定值结果为99.3%,扩展不确定度为0.6%(k=2)。     

宝藿苷Ⅰ纯度标准物质的研制

以淫羊藿提取物为原料,通过正相硅胶柱色谱和凝胶柱色谱等分离纯化手段,研制了宝藿苷Ι纯度标准物质。采用液相色谱–质谱法和核磁共振技术对宝藿苷Ⅰ纯度标准物质进行定性鉴定,利用高效液相色谱(HPLC)法和胶束电动毛细管色谱(MECC)法对宝藿苷Ι的纯度进行定值分析,同时利用HPLC法对宝藿苷Ι纯度标准物质进行均匀性检验与稳定性考察,通过F检验和t检验法对其均匀性进行检验,表明瓶间和瓶内均匀性一致,12个月稳定性检验结果的相对标准偏差为0.02%,说明宝藿苷Ι纯度标准物质是稳定的。对定值结果的不确定度进行了评价,研制的宝藿苷Ι纯度标准物质的定值结果和扩展不确定度分别为99.7%和0.3%(k=2)。     

水中苯甲酸钠标准物质的研制

介绍水中苯甲酸钠标准物质的制备方法。以苯甲酸钠为原料,采用重量–容量法制备溶液标准物质,以液相色谱–紫外可见分光光谱法对标准物质进行均匀性和稳定性检验,并对该标准物质定值结果的不确定度进行评定。结果表明,研制的水中苯甲酸钠标准物质的定值结果为(23.6±0.3) mg/L,有效期为6个月。该标准物质具备良好的均匀性和稳定性,可用于食品防腐剂苯甲酸分析方法的确认与评价。     

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)。     

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。     

磷酸三(2-氯乙基)酯标准物质的研制

研制了有机磷阻燃剂磷酸三(2-氯乙基)酯(TCEP)标准物质。采用硅胶柱层析法对TCEP原料进行纯化,得到纯度大于99%的TCEP纯品。通过红外光谱和气相色谱–质谱准确定性分析后,利用气相色谱法和气相色谱–质谱法结合热重分析法分别对TCEP纯物质进行纯度定值。将制备的50 g TCEP纯品分装到100个小瓶中,每瓶0.5g,从中随机选取10瓶,进行均匀性和稳定性实验,结果表明,研制的TCEP标准物质均匀性良好,在半年内是稳定的。研制的有机磷阻燃剂磷酸三(2-氯乙基)酯标准物质的纯度定值为99.56%,扩展不确定度为1.18%(k=2)。研制的磷酸三(2-氯乙基)酯标准物质满足国家二级标准物质标准的要求。     

铜离子溶液标准物质的比较法定值

对研制的铜单元素溶液标准物质的定值方法进行研究。对原子吸收分光光度法和电感耦合等离子体发射光谱法的准确度和精密度进行比较,确定采用原子吸收分光光度法定值。与一级标准物质比较定值,将质量浓度为1 000μg/mL的铜单元素标准物质稀释得到标准系列,用原子吸收分光光度法分析,绘制标准曲线,用外标法对制备的二级铜单元素溶液标准物质进行定值,定值结果为100.1 mg/L,定值结果的不确定度为1.2 mg/L(k=2)。该定值方法可用于单元素金属标准物质和混合金属标准物质的定值。     

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.     

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....     

肌酐纯度标准物质的定值方法及其不确定度评定研究

通过定性及定量分析,研究了肌酐纯度标准物质的定值方法,并进行了定值分析的不确定度评定。首先使用三重四极杆质谱仪及核磁共振谱仪(氢谱)对肌酐样品进行定性分析,然后采用质量平衡法(包括液相色谱法、水分、灰分、挥发性物质和无机元素分析)与定量核磁共振法共同对肌酐纯度标准物质进行准确定值,最后对定值结果进行不确定度评定。肌酐的定值结果为99.7%,扩展不确定度为0.4%。该研究对于实际检测中肌酐的准确测定及临床上相关疾病的正确诊断治疗具有重要意义,且经过定值的肌酐纯品还可做定量核磁共振法的定量内标使用。定量分析后的肌酐经过均匀性检验和稳定性考察后可申报为国家标准物质。     

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.     

Certified calibration solution reference material for the determination of perfluorooctane sulfonate from the National Metrology Institute of Japan (NMIJ)

A new calibration solution reference material for the determination of perfluorooctane sulfonate anion (PFOS) and its salts has been issued as a certified reference material (CRM) by the National Metrology Institute of Japan, National Institute of Advanced Industrial Science and Technology (NMIJ/AIST). The purity amount-of-substance fraction of raw material potassium perfluorooctane sulfonate (K-PFOS) was evaluated based on the results obtained using the freezing point depression method, and the purity mass fraction of the raw material was calculated using the average molar mass of impurities, the molar mass of K-PFOS, and the purity amount-of-substance fraction. The certified concentration of this CRM was obtained by multiplying the dilution ratio of the raw material in a prepared solution (methanol) determined from the gravimetric blending method by the purity of the raw material. The preparation concentration of K-PFOS as a certified value of NMIJ CRM 4220-a was determined to be 9.93?mg?kg^?1. In addition, the standard uncertainty of the certified value was evaluated from the purity evaluation as well as from sample inhomogeneity, instability, and preparation variation obtained from LC/MS measurements of different gravimetrically prepared solutions of the NMIJ CRM. Consequently, the expanded uncertainty was estimated to be 0.15?mg?kg^?1 with a coverage factor k?=?2 corresponding to the half-width of estimated confidence interval of approximately 95%.     

Certified reference material for the determination of perfluorooctane sulfonate in acrylonitrile-butadiene-styrene resin (NMIJ CRM 8155-a)

A certified reference material (CRM) for the determination of perfluorooctane sulfonate (PFOS) in acrylonitrile-butadiene-styrene (ABS) resin (NMIJ CRM 8155-a) has been issued by the National Metrology Institute of Japan (NMIJ). The bulk material was prepared by mixing commercial ABS resin powder and potassium PFOS and cut into square plates (20 × 20 mm, 2 mm thick) as the CRM. Analytical processes combined with isotope-dilution mass spectrometry and liquid chromatography/mass spectrometry were optimised and applied for characterisation. One of the approaches adopted by NMIJ for certification is that results from two or more primary methods of measurement should be used; thus, two optimised isotope-dilution mass spectrometric methods (Methods 1 and 2 with reprecipitation and with reprecipitation/solid phase extraction, respectively, were validated mutually and employed) were used to determine the certified value. Homogeneity and stability of the square plates were evaluated and their uncertainty contributions (as relative standard uncertainties) were 1.43% for inhomogeneity and 6.96% for approximately two years’ instability. The certified mass fraction of linear PFOS (heptadecafluoro-1-octanesulfonic acid) in the CRM with expanded uncertainty (coverage factor k = 2, approximately 95% confidence interval) was (33.1 ± 5.0) mg kg^?1 as free acid of PFOS.     

Purity determination and uncertainty evaluation of theophylline by mass balance method, high performance liquid chromatography and differential scanning calorimetry

Purity determination of pure organic substance is essential for the establishment of traceability to SI units. A mass balance method was employed to determine the purity of theophylline certified reference materials (CRM), compared with high performance liquid chromatography (HPLC) and differential scanning calorimetry (DSC). In the approach of the mass balance, the impurities were identified by ion trap time-of-flight mass spectrometer (IT-TOF-MS) and quantified by HPLC. The purity of theophylline CRM determined by mass balance method was 99.82% with an extended uncertainty of 0.1% (k = 2). The uncertainty evaluation of purity demonstrated that the accuracy of the mass balance method is better than that of HPLC and DSC. It indicated that the mass balance is suitable for the CRM and pharmaceutical standards.     

Development of a certified reference material for the determination of acrylamide in potato chips

A certified reference material (CRM), KRISS CRM 108-10-003, has been developed for analysis of acrylamide in potato chips, as a representative of carbohydrate-rich food cooked in high-temperature oil. The material was prepared by grinding commercially available potato chips to a paste which was then homogenized, bottled in 15-g units, and stored at ?70 °C. Certification, homogeneity and stability testing, were carried out by liquid chromatography–isotope-dilution mass spectrometry (ID-LC–MS). A single ID-LC–MS measurement was performed for each of 10 selected units for certification and homogeneity assessment. The mean measurement result for the 10 bottles, 0.455?±?0.012 mg?kg^?1, was assigned as the certified value of the CRM. The between-bottle homogeneity was 0.8% of the certified value. The within-bottle homogeneity, tested by measuring three replicate sub-samples from each of three randomly selected bottles, was similar to the between-bottle homogeneity. The stability of the CRM under storage conditions (?70 °C) was tested for 21 months and no change in the acrylamide content was observed within the measurement uncertainty. Stability of the CRM at –20 °C (storage at user’s site) and room temperature (for regular use and transportation) was also tested. Also presented is the newly designed procedure for evaluating the uncertainty of the certified value for the characterization scheme used in this study.