Increased bile acids in enterohepatic circulation by short-term calorie restriction in male mice

Previous studies showed glucose and insulin signaling can regulate bile acid (BA) metabolism during fasting or feeding. However, limited knowledge is available on the effect of calorie restriction (CR), a well-known anti-aging intervention, on BA homeostasis. To address this, the present study utilized a “dose–response” model of CR, where male C57BL/6 mice were fed 0, 15, 30, or 40% CR diets for one month, followed by BA profiling in various compartments of the enterohepatic circulation by UPLC-MS/MS technique. This study showed that 40% CR increased the BA pool size (162%) as well as total BAs in serum, gallbladder, and small intestinal contents. In addition, CR “dose-dependently” increased the concentrations of tauro-cholic acid (TCA) and many secondary BAs (produced by intestinal bacteria) in serum, such as tauro-deoxycholic acid (TDCA), DCA, lithocholic acid, ω-muricholic acid (ωMCA), and hyodeoxycholic acid. Notably, 40% CR increased TDCA by over 1000% (serum, liver, and gallbladder). Interestingly, 40% CR increased the proportion of 12α-hydroxylated BAs (CA and DCA), which correlated with improved glucose tolerance and lipid parameters. The CR-induced increase in BAs correlated with increased expression of BA-synthetic (Cyp7a1) and conjugating enzymes (BAL), and the ileal BA-binding protein (Ibabp). These results suggest that CR increases BAs in male mice possibly through orchestrated increases in BA synthesis and conjugation in liver as well as intracellular transport in ileum.     

阿魏酸长期给药后对大鼠灌服氯沙坦钾的药动学影响

目的 研究长期给药阿魏酸对大鼠体内氯沙坦及其代谢物E-3174的药动学影响。方法 12只健康♂ SD大鼠随机分成2组（每组6只）,试验组每天灌胃50 mg·kg^-1阿魏酸,连续诱导7 d;对照组灌胃等体积0.5%CMC-Na。第8天给药30 min后,给予氯沙坦钾（5 mg·kg^-1）。分别于给药前和给药后0.25,0.5,0.75,1,1.5,2,3,4,6,8,10,12,24 h大鼠尾静脉取血,血样处理后采用UPLC-MS/MS检测大鼠血浆中氯沙坦及E-3174的浓度。结果 虽然2组大鼠体内氯沙坦各项药动学参数对比均无统计学意义,但是试验组大鼠体内E-3174的AUC（0-t）、AUC（0-∞）和Cmax显著增高（P<0.05）;CL/F、Tmax显著降低（P<0.05）。结论 大鼠长期给药阿魏酸后虽然未能引起氯沙坦原形药物药动学的变化,但可使其活性代谢产物E-3174代谢减慢,浓度增高,药时曲线下面积增大。     

UPLC-MS/MS快速测定大鼠血浆中盐酸美沙酮及其代谢产物含量

目的 建立超高效液相色谱-串联质谱（UPLC-MS/MS）测定大鼠血浆中盐酸美沙酮及其代谢产物乙二胺二甲基次磷酸（2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine,EDDP）的含量。方法 以地西泮为内标,大鼠血浆用乙腈沉淀蛋白,运用UPLC-MS/MS检测大鼠灌胃盐酸美沙酮6 mg·kg^-1后血浆中美沙酮和EDDP的血药浓度,并对数据进行分析。结果 大鼠血浆中盐酸美沙酮和EDDP的定量限均为0.5 ng·mL^-1;线性相关系数r>0.999;日内精密度和日间精密度的RSD均<15%;绝对回收率均>85%,相对回收率在90%~110%之间;基质效应在92.80%~97.71%之间。主要药动学参数：美沙酮、EDDP在大鼠血浆中的消除半衰期（t_1/2）为（1.479±0.839）,（2.590±0.760）h;最高血药浓度（C_max）为（48.562±10.501）,（25.542±3.706）μg·L^-1;平均滞留时间（MRT_0-t）为（3.476±0.310）,（3.883±0.514）h;曲线下面积（AUC_0-t）为（204.036±61.145）,（86.031±15.287）μg·h·L^-1;清除率（CL）为（32.338±14.343）、（70.137±10.786）L·h^-1·kg^-1,各项药动学参数比较差异均有统计学意义。结论 该法专属性强、分离完全、快速灵敏,适用于大鼠血浆中盐酸美沙酮及其代谢产物EDDP的含量测定和药动学研究。     

UPLC-MS/MS法测定抗风湿中成药及保健品中非法添加10种抗风湿性化学成分

目的 建立UPLC-MS/MS法检测中成药及保健品中非法添加的10种抗风湿类化学成分的含量。方法 以ACQUITY UPLC BEHC₁₈（50 mm×2.1 mm,1.7 μm）为色谱柱,以含0.1%乙酸0.02 mol/L醋酸铵溶液-乙腈为流动相梯度洗脱,体积流量为0.3 mL/min;质谱采用电喷雾离子源（ESI）,多反应监测（MRM）模式进行定性定量分析。结果 10种化学物质的质谱检测线性范围宽,线性关系良好,r ≥ 0.996 1,平均方法回收率为92.5%~101.8%,RSD为0.9%~3.1%,检出限为0.001 5~0.018 μg,定量限为0.004 5~0.55 μg,27批样品中有10批样品检出了非法添加的化学物质。结论 本方法操作简单,灵敏度高,结果准确,可作为抗风湿类中成药及保健品中非法添加化学物质的测定方法。     

UPLC-MS/MS法同时测定人血浆中地佐辛和罗哌卡因的浓度

目的 建立一种人血浆中地佐辛和罗哌卡因浓度测定的UPLC-MS/MS法.方法 血浆样品经乙腈沉淀蛋白后提取处理,以利多卡因为内标.色谱柱:Agilent Zorbax Eclipse Plus C18;流动相:0.1％甲酸铵溶液-甲醇(75:25,用甲酸调节pH至4.5),流速:0.2 mL·min-1,柱温:35℃,...     

Potential Health Risk Associated with Mycotoxins in Oat Grains Consumed in Spain

Spain is a relevant producer of oats (Avena sativa), but to date there has been no study on the occurrence/co-occurrence of mycotoxins in oats marketed in Spain. The present study is addressed to overcome this lack of knowledge. One hundred oat kernel samples were acquired across different Spanish geographic regions during the years 2015–2019 and analyzed for mycotoxin content using an ultra-high performance liquid chromatography electrospray ionization tandem mass spectrometry (UPLC–ESI–MS/MS) method and matrix-matched calibration. The focus was on the regulated mycotoxins although other relevant mycotoxins were considered. The percentage of incidence (levels ≥ limit of detection), mean and range (ng/g) of mycotoxins were as follows: zearalenone (66%, mean 39.1, range 28.1–153), HT-2 toxin (47%, mean 37.1, range 4.98–439), deoxynivalenol, (34%, mean 81.4, range 19.1–736), fumonisin B1 (29%, mean 157.5, range 63.2–217.4), and T-2 toxin, (24%, mean 49.9, range 12.3–321). Fumonisin B2, 3-acetyldeoxynivalenol, aflatoxins B1, B2, and G2, and ochratoxin A were also detected at low levels, but aflatoxin G1 was not. The maximum limits established by the European Commission for unprocessed oats were not exceeded, except for zearalenone (in one sample), and the sum of aflatoxins (in two samples). Mycotoxin co-occurrence at quantifiable levels in the same sample (two to five combinations) was found in 31% of samples. The most common mixtures were those of HT-2 + T-2 toxins alone or together with deoxynivalenol and/or zearalenone.     

苦碟子注射液对血栓通主要皂苷成分药物动力学的影响

目的研究苦碟子注射液对血栓通(冻干)中三七皂苷R1、人参皂苷Rg1、人参皂苷Re、人参皂苷Rb1和人参皂苷Rd在大鼠体内药动学特征的影响。方法 12只SD大鼠随机分为2组,分别为血栓通组、苦碟子注射液-血栓通配伍组,尾静脉注射,于给药后不同时间采集血样,血样经乙腈沉淀蛋白后取上清,采用超高效液相色谱串联三重四级杆质谱(UPLC-MS/MS)测定5个皂苷成分的血药浓度。结果与苦碟子注射液配伍后,血栓通中5个化合物的t1/2、AUC0^t、AUC0t、AUC0^∞、CL、MRT0∞、CL、MRT0^t、MRT0t、MRT0^∞、Vd等主要药物动力学参数有不同程度的改变。结论苦碟子注射液在一定程度上能影响血栓通中主要皂苷成分在大鼠体内的药动学特征。     

UPLC-MS/MS法同时测定人血浆中卡马西平、拉莫三嗪、氯硝西泮、地西泮及其代谢物奥沙西泮浓度

目的 建立同时测定人血浆中卡马西平、拉莫三嗪、氯硝西泮、地西泮及其代谢物奥沙西泮浓度的方法。方法 采用超高效液相色谱-质谱联用法（UPLC-MS/MS）,以磺胺甲噁唑（SMZ）为内标,血浆经甲醇直接沉淀后进样分析。色谱柱为WatersACQUITYUPLCHSSPFP柱（2.1mm×100mm,1.8μm）,流动相为0.1%甲酸的5mmol·L1乙酸铵水溶液-0.1%甲酸的甲醇溶液（0~5min,35∶65→10∶90）,流速为0.2mL·min1。电喷雾离子源,正离子多反应监测扫描分析,卡马西平、拉莫三嗪、氯硝西泮、地西泮和奥沙西泮的离子对分别为m/z237.0→194.06、m/z255.98→144.95、m/z316.01→270.0、m/z285.04→193.07和m/z287.02→241;内标磺胺甲噁唑的离子对为m/z253.96→91.97。结果 卡马西平、拉莫三嗪、氯硝西泮、地西泮和奥沙西泮血药浓度分别在2.4~600ng·mL1（r=0.9997）,2.52~630ng·mL1（r=0.9920）,2.08~520ng·mL1（r=0.9979）,2.28~570ng·mL1（r=0.9982）,8.0~800ng·mL1（r=0.9992）线性关系良好;最低检出限分别为0.24,0.63,0.52,0.57,3.2ng·mL1。日内、日间精密度均〈15%;提取回收率均〉70%,且RSD〈15%。结论 该方法灵敏、快速、专属性强,可用于临床血药浓度测定及药动学研究。     

“天麻胶囊”质量标准中补充检验吲哚美辛的方法

目的:建立天麻胶囊中非法添加吲哚美辛的检测方法.方法:采用TLC快速筛选、HPLC-PDA法进行定量检验以及UPLC-MS法进行结构确认.结果:建立的方法能鉴别并确认添加的吲哚美辛,灵敏度高,专属性好.结论:该方法简便、快速,结果准确,可用于检测天麻胶囊中非法加入的吲哚美辛成分.     

大鼠ig牡丹皮提取物后丹皮酚及其代谢产物的药动学研究

目的 考察ig给予大鼠牡丹皮提取物后,丹皮酚及4种主要代谢产物M1~M4在大鼠体内的药动学特征。方法 SD雄性大鼠ig给予不同剂量（0.5、1.0、2.0 g/kg）牡丹皮提取物,于各时间点从大鼠眼底静脉丛取血,收集血浆样品;ig给予1.0 g/kg的牡丹皮提取物,按相应时间段收集大鼠尿液、胆汁和粪便样品。生物样品用乙腈（含0.1%甲酸）沉淀蛋白的方法处理,用建立的超高效液相色谱串联质谱（UPLC-MS/MS）分析方法检测生物样品中丹皮酚及其4种代谢产物质量浓度。结果 建立的生物样品分析方法符合分析要求。ig给予大鼠不同剂量（0.5、1.0、2.0 g/kg）牡丹皮提取物后,丹皮酚的t_max分别为（0.15±0.08）、（0.33±0.19）、（0.31±0.13）h;t_1/2为（1.16±0.37）、（1.19±0.45）、（1.24±0.35）h;C_max和AUC_0~t随给药剂量的增加而增大,具有剂量依赖性。M1~M4在给药后1 h内也相继达到峰浓度。ig给予1.0 g/kg的牡丹皮提取物后,丹皮酚的代谢产物主要排泄方式为尿液 > 胆汁 > 粪便。结论 大鼠ig给予牡丹皮提取物后,丹皮酚具有快速吸收、代谢及消除的特点,丹皮酚主要通过尿液途径以代谢产物形式排泄。