The standards of plant toxins were separated by a C18 column with gradient elution with 0.1% formic acid/water (V/V) and 0.1% formic acid/acetonitrile (V/V) as mobile phase and acquired by ion mobility-quadrupole time...The standards of plant toxins were separated by a C18 column with gradient elution with 0.1% formic acid/water (V/V) and 0.1% formic acid/acetonitrile (V/V) as mobile phase and acquired by ion mobility-quadrupole time of flight mass spectrometry (IM-QTOF MS) in positive ion mode. A database of 308 plant toxins including retention time, collision cross-section (CCS) and its fragment ions was established. Honey dissolved in water or herbal beverage was extracted by acetonitrile and purified with PSA sorbent, and then acquired by ultrahigh-performance liquid chromatography IM-QTOFMS. The acquired data were processed by comparing with the database we established to confirm the target compounds. The average recoveries for samples at two levels ranged from 60.6% - 120.1%, with relative standard deviation (n = 6) less than 25%. The limit of quantitation for plant toxins ranged from 1 - 20 μg/kg. The developed screening method was used in determination of honey, herbal beverage and honey flavored tea beverage samples. The results showed that berberine was detected in one honey with 1 μg/kg and caffeine was present in some beverages with the concentration from 200 and 5500 μg/kg. This method could meet the requirement for rapid screening of plant toxins in honey and herbal beverage. It can be used for the quality control of honey and herbal beverage in enterprises or quality inspection departments. It also can be used in the rapid screening of food poisoning.展开更多
OBJECTIVE:To identify the active ingredients and metabolites in rat bile after Guangtongxiao decoction(GTX)had been administered via the rectal route.METHODS:Drug-containing bile samples were collected via a catheter ...OBJECTIVE:To identify the active ingredients and metabolites in rat bile after Guangtongxiao decoction(GTX)had been administered via the rectal route.METHODS:Drug-containing bile samples were collected via a catheter in the bile duct and could be used 5 h after rectal administration.The main active components and their metabolites in rat bile following rectal administration of GTX were identified and analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.RESULTS:Positive and negative modes were applied to analyze and identify the chemical ingredients in the bioactive fractions of GTX.Eight peaks were identified by comparison with the standard compounds:berberine hydrochloride,dehydrocorydaline,tetrahydropalmatine,corydaline,magnoflorine,magnolol,obacunone and albiflorin.Furthermore,60 metabolites were detected in rat bile based on mass-fragmentation behaviors,and 21 metabolites were reported for the first time.CONCLUSION:Our findings provide a solid basis for further pharmacologic and pharmacokinetic studies of GTX.展开更多
目的·探究KRAS靶向抑制剂索托拉西布(sotorasib)获得性耐药肺癌细胞的代谢特征及代谢重编程规律。方法·构建肺癌细胞H2122和H358的索托拉西布获得性耐药细胞模型(H2122-SR和H358-SR细胞),并采用CCK-8法加以验证。应用超高效...目的·探究KRAS靶向抑制剂索托拉西布(sotorasib)获得性耐药肺癌细胞的代谢特征及代谢重编程规律。方法·构建肺癌细胞H2122和H358的索托拉西布获得性耐药细胞模型(H2122-SR和H358-SR细胞),并采用CCK-8法加以验证。应用超高效液相色谱串联四极杆飞行时间质谱(UPLC-QTOF/MS)分析获得性耐药肺癌细胞及其同源亲本细胞的代谢轮廓,利用主成分分析法和偏最小二乘法-判别分析法等统计学方法进行非靶向代谢组学分析及代谢表征,筛选并鉴定索托拉西布获得性耐药相关的差异代谢物,并对所筛选到的差异代谢物进行通路富集分析。通过绘制热图比较分析主要差异代谢通路上的代谢物在耐药细胞与亲本细胞之间的差异。结果·成功构建H2122和H358细胞的获得性耐药细胞模型,对索托拉西布的半数抑制浓度均较亲本细胞提升50倍以上。与亲本细胞相比,耐药细胞代谢轮廓存在显著差异。H2122-SR与H2122细胞之间发现48种差异代谢物,其中变量投影重要程度(variable importance in the projection,VIP)值排名前10位的差异代谢物为尿嘧啶、黄苷酸、吲哚-3-甲酸、烟酸、黄苷、黄嘌呤、N-甲基烟酰胺、次黄嘌呤、葫芦巴碱、半乳糖醛酸;H358-SR与H358细胞之间发现79种差异代谢物,其中VIP值排名前10位的差异代谢物为还原型谷胱甘肽、黄苷、α-酮戊二酸、羧甲基赖氨酸、胸苷、嘌呤、核黄素、3-吲哚丙烯酸、吲哚-3-丙酮酸、二氢尿嘧啶。2种肺癌细胞系的差异代谢通路主要涉及嘌呤代谢和糖酵解/糖异生,其中嘌呤代谢变化最为显著。热图分析显示,耐药细胞嘌呤代谢途径多数代谢物水平升高。结论·索托拉西布获得性耐药的肺癌细胞嘌呤代谢增强。展开更多
目的建立一种基于超高效液相色谱-四极杆-飞行时间高分辨质谱法(ultra performance liquid chromatography-quadrupole time of flight high resolution-mass spectrometry,UPLC-Q-TOF-MS)用于中兽药中的302种药物非法添加的快速筛查方...目的建立一种基于超高效液相色谱-四极杆-飞行时间高分辨质谱法(ultra performance liquid chromatography-quadrupole time of flight high resolution-mass spectrometry,UPLC-Q-TOF-MS)用于中兽药中的302种药物非法添加的快速筛查方法。方法建立了包含302种药物名称、分子式、精确质量数等信息的高分辨质谱数据库。样品经甲醇提取后,经过UPLC-Q-TOF-MS进行数据采集并分析,当保留时间与数据库绝对偏差<0.2 min,质量误差<5 ppm,同位素比值偏差<5%,且主要特征碎片离子的库比对分数>80时,认为检出疑似阳性样品。结果该方法选择性较好,目标物最低检出质量浓度低至50 ng/mL(四环素类、青霉素类、雌激素类、及非甾体抗炎药检出质量浓度100 ng/mL;氨基糖苷类检出质量浓度200 ng/mL),实现了302种非法添加药物的高效筛查。实际样品筛查时,检出了7批疑似阳性样品。结论本研究建立的筛查手段具有快速、广谱的特点,适用于多种中兽药中的非法添加药物的初步筛查,为中兽药质量控制提供了有效技术支持。展开更多
文摘The standards of plant toxins were separated by a C18 column with gradient elution with 0.1% formic acid/water (V/V) and 0.1% formic acid/acetonitrile (V/V) as mobile phase and acquired by ion mobility-quadrupole time of flight mass spectrometry (IM-QTOF MS) in positive ion mode. A database of 308 plant toxins including retention time, collision cross-section (CCS) and its fragment ions was established. Honey dissolved in water or herbal beverage was extracted by acetonitrile and purified with PSA sorbent, and then acquired by ultrahigh-performance liquid chromatography IM-QTOFMS. The acquired data were processed by comparing with the database we established to confirm the target compounds. The average recoveries for samples at two levels ranged from 60.6% - 120.1%, with relative standard deviation (n = 6) less than 25%. The limit of quantitation for plant toxins ranged from 1 - 20 μg/kg. The developed screening method was used in determination of honey, herbal beverage and honey flavored tea beverage samples. The results showed that berberine was detected in one honey with 1 μg/kg and caffeine was present in some beverages with the concentration from 200 and 5500 μg/kg. This method could meet the requirement for rapid screening of plant toxins in honey and herbal beverage. It can be used for the quality control of honey and herbal beverage in enterprises or quality inspection departments. It also can be used in the rapid screening of food poisoning.
基金Supported by the Youth Program of National Natural Science Foundation of China(To Investigate the Spasmolysis of Intestinal Absorption Solution of Guang Tong Xiao Aqueous Extract&Effective Components for Anal Sphincter Based on Calcium Channels,No.81704077)。
文摘OBJECTIVE:To identify the active ingredients and metabolites in rat bile after Guangtongxiao decoction(GTX)had been administered via the rectal route.METHODS:Drug-containing bile samples were collected via a catheter in the bile duct and could be used 5 h after rectal administration.The main active components and their metabolites in rat bile following rectal administration of GTX were identified and analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.RESULTS:Positive and negative modes were applied to analyze and identify the chemical ingredients in the bioactive fractions of GTX.Eight peaks were identified by comparison with the standard compounds:berberine hydrochloride,dehydrocorydaline,tetrahydropalmatine,corydaline,magnoflorine,magnolol,obacunone and albiflorin.Furthermore,60 metabolites were detected in rat bile based on mass-fragmentation behaviors,and 21 metabolites were reported for the first time.CONCLUSION:Our findings provide a solid basis for further pharmacologic and pharmacokinetic studies of GTX.
文摘目的·探究KRAS靶向抑制剂索托拉西布(sotorasib)获得性耐药肺癌细胞的代谢特征及代谢重编程规律。方法·构建肺癌细胞H2122和H358的索托拉西布获得性耐药细胞模型(H2122-SR和H358-SR细胞),并采用CCK-8法加以验证。应用超高效液相色谱串联四极杆飞行时间质谱(UPLC-QTOF/MS)分析获得性耐药肺癌细胞及其同源亲本细胞的代谢轮廓,利用主成分分析法和偏最小二乘法-判别分析法等统计学方法进行非靶向代谢组学分析及代谢表征,筛选并鉴定索托拉西布获得性耐药相关的差异代谢物,并对所筛选到的差异代谢物进行通路富集分析。通过绘制热图比较分析主要差异代谢通路上的代谢物在耐药细胞与亲本细胞之间的差异。结果·成功构建H2122和H358细胞的获得性耐药细胞模型,对索托拉西布的半数抑制浓度均较亲本细胞提升50倍以上。与亲本细胞相比,耐药细胞代谢轮廓存在显著差异。H2122-SR与H2122细胞之间发现48种差异代谢物,其中变量投影重要程度(variable importance in the projection,VIP)值排名前10位的差异代谢物为尿嘧啶、黄苷酸、吲哚-3-甲酸、烟酸、黄苷、黄嘌呤、N-甲基烟酰胺、次黄嘌呤、葫芦巴碱、半乳糖醛酸;H358-SR与H358细胞之间发现79种差异代谢物,其中VIP值排名前10位的差异代谢物为还原型谷胱甘肽、黄苷、α-酮戊二酸、羧甲基赖氨酸、胸苷、嘌呤、核黄素、3-吲哚丙烯酸、吲哚-3-丙酮酸、二氢尿嘧啶。2种肺癌细胞系的差异代谢通路主要涉及嘌呤代谢和糖酵解/糖异生,其中嘌呤代谢变化最为显著。热图分析显示,耐药细胞嘌呤代谢途径多数代谢物水平升高。结论·索托拉西布获得性耐药的肺癌细胞嘌呤代谢增强。
文摘目的建立一种基于超高效液相色谱-四极杆-飞行时间高分辨质谱法(ultra performance liquid chromatography-quadrupole time of flight high resolution-mass spectrometry,UPLC-Q-TOF-MS)用于中兽药中的302种药物非法添加的快速筛查方法。方法建立了包含302种药物名称、分子式、精确质量数等信息的高分辨质谱数据库。样品经甲醇提取后,经过UPLC-Q-TOF-MS进行数据采集并分析,当保留时间与数据库绝对偏差<0.2 min,质量误差<5 ppm,同位素比值偏差<5%,且主要特征碎片离子的库比对分数>80时,认为检出疑似阳性样品。结果该方法选择性较好,目标物最低检出质量浓度低至50 ng/mL(四环素类、青霉素类、雌激素类、及非甾体抗炎药检出质量浓度100 ng/mL;氨基糖苷类检出质量浓度200 ng/mL),实现了302种非法添加药物的高效筛查。实际样品筛查时,检出了7批疑似阳性样品。结论本研究建立的筛查手段具有快速、广谱的特点,适用于多种中兽药中的非法添加药物的初步筛查,为中兽药质量控制提供了有效技术支持。
