An analytical method for the quantification of residual solvents in annatto extracts, natural food colorants, was established using a static headspace gas chromatography (HSGC) coupled with a flame ionization detector...An analytical method for the quantification of residual solvents in annatto extracts, natural food colorants, was established using a static headspace gas chromatography (HSGC) coupled with a flame ionization detector (FID). As a sample diluent in a headspace sampling, dimethylformamide (DMF) was selected owing to its high capacity for dissolving both bixin-based and norbixin-based annatto extracts. The quantification of residual solvents was performed using the external standard method. The linearity of the calibration curves was assured with relative coefficients (R2) that were greater than 0.999. The recoveries of all standard solvents spiked in the annatto extracts were in the range from 95.1% to 107.1% to verify the accuracy and the relative standard deviation (RSD%) values (n = 3) were in the range from 0.57% to 3.31%. The quantification limits (QL) were sufficiently lower than the limits specified by Joint FAO/WHO Expert Committee on Food Additives (JECFA). With the established HSGC method, six residual solvents (methanol, ethanol, 2-propanol, acetone, ethyl acetate, and hexane) in 23 commercial annatto-extract products that consist of seven bixin-based and 16 norbixin-based products were quantified. The levels of residual ethyl acetate and hexane in all products were lower than the specified limits of JECFA. However, three samples of bixin-based products showed higher levels of residual 2-propanol (approximately 313.9 - 427.7 ppm) than the specified limit. Other bixin products also showed higher concentrations of residual methanol (approximately 166.6 - 394.7 ppm) and residual acetone (approximately 75.2 - 179.8 ppm) than the limits of JECFA. In the case of norbixin-based products, nine samples showed higher levels of residual acetone (approximately 42.6 - 139.5 ppm) than the limits of JECFA. This is the first survey of residual solvents in annatto extracts using the validated HSGC method.展开更多
In drug discovery research, residual solvent measurement is an integral part of purity analysis for synthesis of a drug candidate before it is used for toxicity testing. This is usually carried out using gas chromatog...In drug discovery research, residual solvent measurement is an integral part of purity analysis for synthesis of a drug candidate before it is used for toxicity testing. This is usually carried out using gas chromatography(GC)with direct injection sample introduction. This method requires testing compounds to be soluble at high concentrations( > 50 mg/mL, usually in DMSO) to achieve acceptable sensitivity, a hurdle which is not always achievable for some samples such as cyclic peptides and oligonucleotides. To overcome the limitation associated with the direct injection approach, a new method using the Chromatoprobe thermal extraction device was developed for quantifying residual solvents of drug discovery compounds. This method not only consumes significantly less material(less than 1 mg), but also shows higher sensitivity than the direct injection approach.In addition, because no diluent is required with the Chromatoprobe thermal extraction, all residual solvents can be detected and measured without further method optimization. In our study, we compared data from GC residual solvent analysis using the Chromatoprobe solid sample introduction to those of the direct injection method for seven in-house samples. Our results showed a good agreement between the data from these two sample introduction methods. Thus, the Chromatoprobe sample introduction method provided a samplesparing alternative to the direct injection method for the measurement of residual solvents in drug discovery.This method can be particularly useful for residual solvent analysis in samples that are available only in limited amounts, poorly soluble, and/or unstable in the diluents used for the direct injection method.展开更多
目的:建立硫酸氢氯吡格雷原料药中所含7种有机溶剂(甲苯、四氢呋喃、正己烷、甲醇、二氯甲烷、丙酮和异丙醇)残留量的测定方法。方法:以DB-1毛细管柱(30 m×0.32 mm, 3.0μm)为色谱柱,程序升温,火焰离子化检测器。进样口温度为200℃...目的:建立硫酸氢氯吡格雷原料药中所含7种有机溶剂(甲苯、四氢呋喃、正己烷、甲醇、二氯甲烷、丙酮和异丙醇)残留量的测定方法。方法:以DB-1毛细管柱(30 m×0.32 mm, 3.0μm)为色谱柱,程序升温,火焰离子化检测器。进样口温度为200℃,分流比为5∶1,检测器温度为270℃。载气为高纯N_(2),恒流控制,流速为4 mL·min^(-1)。顶空进样器的平衡温度为85℃,平衡时间为20 min。结果:7种溶剂均能完全分离,各组分的质量浓度与峰面积呈良好的线性关系(r>0.999 3),方法的专属性、重复性和准确度均符合要求。结论:本法适用于硫酸氢氯吡格雷原料药中有机溶剂残留量的测定。展开更多
文摘An analytical method for the quantification of residual solvents in annatto extracts, natural food colorants, was established using a static headspace gas chromatography (HSGC) coupled with a flame ionization detector (FID). As a sample diluent in a headspace sampling, dimethylformamide (DMF) was selected owing to its high capacity for dissolving both bixin-based and norbixin-based annatto extracts. The quantification of residual solvents was performed using the external standard method. The linearity of the calibration curves was assured with relative coefficients (R2) that were greater than 0.999. The recoveries of all standard solvents spiked in the annatto extracts were in the range from 95.1% to 107.1% to verify the accuracy and the relative standard deviation (RSD%) values (n = 3) were in the range from 0.57% to 3.31%. The quantification limits (QL) were sufficiently lower than the limits specified by Joint FAO/WHO Expert Committee on Food Additives (JECFA). With the established HSGC method, six residual solvents (methanol, ethanol, 2-propanol, acetone, ethyl acetate, and hexane) in 23 commercial annatto-extract products that consist of seven bixin-based and 16 norbixin-based products were quantified. The levels of residual ethyl acetate and hexane in all products were lower than the specified limits of JECFA. However, three samples of bixin-based products showed higher levels of residual 2-propanol (approximately 313.9 - 427.7 ppm) than the specified limit. Other bixin products also showed higher concentrations of residual methanol (approximately 166.6 - 394.7 ppm) and residual acetone (approximately 75.2 - 179.8 ppm) than the limits of JECFA. In the case of norbixin-based products, nine samples showed higher levels of residual acetone (approximately 42.6 - 139.5 ppm) than the limits of JECFA. This is the first survey of residual solvents in annatto extracts using the validated HSGC method.
文摘In drug discovery research, residual solvent measurement is an integral part of purity analysis for synthesis of a drug candidate before it is used for toxicity testing. This is usually carried out using gas chromatography(GC)with direct injection sample introduction. This method requires testing compounds to be soluble at high concentrations( > 50 mg/mL, usually in DMSO) to achieve acceptable sensitivity, a hurdle which is not always achievable for some samples such as cyclic peptides and oligonucleotides. To overcome the limitation associated with the direct injection approach, a new method using the Chromatoprobe thermal extraction device was developed for quantifying residual solvents of drug discovery compounds. This method not only consumes significantly less material(less than 1 mg), but also shows higher sensitivity than the direct injection approach.In addition, because no diluent is required with the Chromatoprobe thermal extraction, all residual solvents can be detected and measured without further method optimization. In our study, we compared data from GC residual solvent analysis using the Chromatoprobe solid sample introduction to those of the direct injection method for seven in-house samples. Our results showed a good agreement between the data from these two sample introduction methods. Thus, the Chromatoprobe sample introduction method provided a samplesparing alternative to the direct injection method for the measurement of residual solvents in drug discovery.This method can be particularly useful for residual solvent analysis in samples that are available only in limited amounts, poorly soluble, and/or unstable in the diluents used for the direct injection method.
