LC-MS/MS法测定大鼠血浆中芍药内酯苷的浓度及其在毒代动力学研究中的应用

目的 建立测定大鼠血浆中芍药内酯苷的液相色谱-串联质谱(LC-MS/MS)法.方法 血浆样品经乙酸乙酯-异丙醇(95:5,V/V)提取后,以Poroshell 120 EC-C18柱(50 mm×2.1 mm,2.7μm)为分析柱,乙腈-水为流动相梯度洗脱,采用ESI源在多反应监测(MRM)方式下进行正离子检测.用于定量分析的离子反应为m/z 498.5→m/z 197.1(芍药内酯苷)和m/z 251.3→m/z 108.2(拉科酰胺,内标).结果 芍药内酯苷血浆浓度测定方法的线性范围为20~2000 ng/ml,日内、日间精密度RSD%均<15%,准确度(RE)在±8.06%之间.结论 该法适用于芍药内酯苷在大鼠体内的毒代动力学研究.     

HPLC-MS/MS法测定大鼠血浆中麻黄碱、伪麻黄碱浓度及药动学研究

[目的]建立同时检测大鼠血浆中麻黄碱、伪麻黄碱的高效液相色谱-质谱联用法(HPLC-MS/MS),并对大鼠口服三拗汤后的麻黄碱、伪麻黄碱进行药代动力学研究。[方法]血浆样品经碱化和乙酸乙酯液-液萃取,以盐酸苯丙醇胺为内标,乙腈-0.1%甲酸水(4∶96)为流动相,经Agilent Zorbax SB-C18柱(4.6 mm×150 mm,5μm)分离,采用电喷雾离子源(ESI),以多反应监测(MRM)模式进行正离子检测,定量分析的离子反应分别为:m/z 166.2→m/z 148.2(麻黄碱),m/z 166.2→m/z 148.2(伪麻黄碱)和m/z 152.1→m/z 134.1(盐酸苯丙醇胺)。[结果]麻黄碱和伪麻黄碱血药浓度在20~10 000μg/L范围内线性关系良好,批内、批间精密度RSD均小于5.3%,高、中、低3种浓度平均方法回收率大于64.7%。[结论]该方法专属、快速、灵敏,可用于麻黄碱、伪麻黄碱的药代动力学研究。     

高效液相色谱-质谱-质谱联用法测定Beagle狗血浆中石杉碱甲

目的:建立狗血浆中石杉碱甲的液质联用测定法.方法:血浆样品经液液萃取,用高效液相色谱-质谱-质谱联用法检测.色谱柱为Nucleocil ODS柱,50×2.0 mm I.D.,5 μm,流动相为乙腈-甲醇-水-甲酸(20∶40∶40∶0.1,v/v).采用多反应监测,用于定量的离子为m/z 243→210(石杉碱甲)和m/z 257→226(内标N-甲基石杉碱甲).结果:线性范围为0.1～12 ng/ml,最低定量浓度为0.1 ng/ml,可以检测到Beagle狗静注和口服100 μg石杉碱甲后12 h的血药浓度.结论:该方法灵敏度高,简便快速,可用于药代动力学研究.     

HPLC-MS/MS法测定人血浆中普罗布考浓度

目的建立高效液相色谱-串联质谱(HPLC-MS/MS)技术测定人血浆中普罗布考浓度的方法。方法血浆经乙酸乙酯∶二氯甲烷(1∶1,V/V)提取后,采用HPLC-MS/MS测定。以ultimate CN(50mm×4.6mm,5μm)为色谱柱,乙腈∶水∶氨水=97∶3∶0.05(甲酸调pH=7.20)为流动相进行分离。质谱采用负离子模式检测,以大黄素甲醚为内标,检测离子515.5→236.1(普罗布考)和283.0→239.9(内标)。结果普罗布考在2.5～6000ng/mL范围内线性关系良好,最低定量限为2.5ng/mL,方法回收率在93.02%～104.12%之间,日内、日间精密度分别小于4.67%及5.72%。结论本研究所建立的方法准确、灵敏,可用于普罗布考血药浓度测定及药代动力学研究。     

液相色谱-串联质谱法测定大鼠血浆中脱水穿心莲内酯琥珀酸半酯的含量(英文)

目的建立了测定大鼠血浆中脱水穿心莲内酯琥珀酸半酯(DAS)的液相色谱-串联质谱法。方法血浆样品经液-液萃取后,以甲醇-水(70∶30,V/V)为流动相,通过Restek PinnacleⅡC18柱分离,格列吡嗪为内标,选择负离子扫描方式,以多反应监测(MRM)方式进行检测。用于定量分析的离子反应分别为m/z 531→m/z 431(DAS)和m/z 444→m/z319(格列吡嗪,内标)。结果DAS血浆浓度测定方法的线性范围为5～2500 ng/ml,定量下限为5 ng/ml。日内、日间精密度(RSD)均小于9.51%,准确度(RE)在-0.18%~1.93%。样品提取回收率为79.73%~85.99%,每个样品的测试时间为3 min。应用此法测试了大鼠口服或静注穿琥宁(DAS的单钾盐)后DAS的血药浓度,计算出其绝对生物利用度为3.69%。结论本方法灵敏度高、专属性强,适合于DAS的临床前药动学研究。     

液相色谱-串联质谱法同时测定小鼠血浆中CTN986、芦丁和曲克芦丁的浓度及其在药动学研究中的应用

目的 建立同时测定小鼠血浆中CTN986、芦丁和曲克芦丁浓度的LC-MS/MS法并将其应用于小鼠药代动力学研究.方法 血浆样品经固相萃取后,以甲醇-异丙醇-水-甲酸(体积比为36∶8∶56∶0.1)为流动相,通过Discovery C18柱(250 mm×4.6 mm,5μm)分离,采用ESI源以多反应监测(MRM)方式进行正离子检测.用于定量分析的离子反应分别为m/z 743→m/z 303(CTN986),m/z 611→m/z 303(芦丁),m/z 745→m/z 435(曲克芦丁),m/z 727→m/z 287(CTN987,内标).结果 CTN986、芦丁和曲克芦丁的线性范围均为4～ 800 ng/ml,日内、日间精密度(RSD)均小于14.65％,准确度(RE)在-0.34％ ～ 11.75％.应用此法考察了小鼠口服和静注上述3个化合物后的药动学特征,以及P-gp抑制剂维拉帕米对三者药动学行为的影响.结论 本方法专属性强、灵敏度高,适用于CTN986、芦丁和曲克芦丁的药代动力学研究.     

高效液相色谱-质谱法测定宣肺止嗽合剂中吗啡含量

目的建立高效液相色谱-质谱(HPLC-MS)法测定宣肺止嗽合剂中吗啡含量的方法。方法采用HPLC-MS正离子多反应监测模式(MRM)测定宣肺止嗽合剂中吗啡的含量,色谱柱为Shim-pack GIST-HP C18柱(50.0 mm×2.1 mm,3μm),流动相为甲醇-0.1%甲酸(30∶70,V/V),流速0.3 m L/min,柱温40℃;采用电喷雾离子源(ESI),以MRM进行定量分析,吗啡在正离子模式下定量分析离子对m/z 286. 40→m/z201.10。结果吗啡在0.517 5～5.175 0μg/m L质量浓度范围内线性关系良好(r=0.999 3);平均加样回收率为98.34%,RSD为1.44%;最低检测限为0.207 ng/m L,最低定量限为0.414 ng/m L。结论该方法简单可靠、重复性好,适用于药品中低含量吗啡的检测。     

HPLC-MS/MS法测定人血浆中氨溴索浓度

目的建立测定人血浆中盐酸氨溴索浓度的液相色谱-质谱-质谱联用法(HPLC-MS-MS)。方法血浆中加入内标曲马多,经液-液萃取后离心,取上清液吹干,再用甲醇复溶。色谱系统:SYMMETRYTM C18柱(150 mm&#215;3.9 mm,5μm),流动相由20 mmo.ll-1乙酸铵水溶液∶甲醇(10∶90)组成,流速为0.6 ml.min-1。质谱检测方式:多重反应监测(MRM)。用于定量分析的离子对分别为质荷比(m/z)379.0→m/z 263.9(氨溴索)和m/z 264.2→m/z 58.1(内标曲马多)。结果盐酸氨溴索线性范围为0.1~400.0 ng.ml-1,最低检测浓度为0.1 ng.ml-1;标准曲线相关系数r≥0.99。结论HPLC-MS/MS法具有专属、灵敏、准确、操作简单及快速的优点,可以用于测定人血浆氨溴索浓度。     

HPLC-MS/MS法测定人血浆中阿戈美拉汀的浓度

目的采用高效液相色谱-串联质谱(HPLC-MS/MS)法测定人血浆中阿戈美拉汀血药浓度,并将该方法应用于药动学研究中。方法血浆样品经碱化后,采用乙酸乙酯-二氯甲烷(体积比4∶1)萃取,以托莫西汀为内标,采用HPLC-MS/MS法测定。色谱柱为Agilent Eclipse plus C18(4.6 mm×150 mm,3.5μm),流动相为甲醇-水(体积比95∶5,含0.005 mol.L-1甲酸铵和质量分数0.1%甲酸),流速为0.5 mL.min-1,柱温为40℃;质谱条件采用ESI离子源,检测方式为正离子电离,选择性离子检测(MRM),阿戈美拉汀m/z为244.2→185.2,托莫西汀m/z为256.1→44.1。结果阿戈美拉汀质量浓度在0.025～10μg.L-1范围内线性关系良好,提取回收率在84.45%～86.94%之间,批内、批间精密度分别小于3.76%、12.23%。结论本文建立的用于测定人血浆中阿戈美拉汀的HPLC-MS/MS方法快速、准确、灵敏,可用于药动学研究及治疗药物监测。     

LC-MS/MS法同时测定Beagle犬血浆中柚皮苷和新橙皮苷的含量

目的:建立同时测定Beagle犬血浆中柚皮苷和新橙皮苷的LC-MS/MS分析方法。方法:以芦丁为内标,血浆样品经乙腈沉淀蛋白处理,采用Diamonsil C18(150 mm×4.6 mm,5μm)色谱柱,以乙腈-0.1%甲酸水(25:75)为流动相,流速为0.4 ml/min,柱温20℃;采用ESI(+)离子源,MRM扫描检测离子对为柚皮苷m/z 581→273、新橙皮苷m/z 611→303、芦丁(内标)m/z611→303。结果:血浆中柚皮苷在0.025～2.5μg/ml、新橙皮苷在0.015～1.5μg/ml浓度范围内线性关系良好,二者的方法回收率均近100%,分析方法的日内日间精密度RSD值均小于10%,内源性物质不干扰样品测定。结论:本方法简便、准确、灵敏度高、专属性好,适用于Beagle犬血浆中柚皮苷和新橙皮苷测定及其体内药代动力学的研究。     

APPLICATION OF LORNOXICAM TO PATIENT-CONTROLLED ANALGESIA IN PATIENTS UNDERGOING ABDOMINAL SURGERIES

FOR anesthesiologis s ,treatingpostoperativepainhas alwaysbeen a problem.Althoughopioidshave been provedtobe effective,theirsideeffectscouldnotbeignored.With thedevelopmentofscienceand pharmacology,many drugs with aspectsof satisfactoryanalgesicefficacyand couldbe welltoleratedby patientshave been developed.And lornoxicamisone of them, which isa non-steroidalanti-inflammatorydrug (NSAID ), with analgesic, anti-infl-ammatory,andantipyreticproperties.Itseliminationhalf-time(3 to 5 hours) isle…     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

Acupuncture Combined with Spinal Tui Na for Treatment of Primary Dysmenorrhea in 30 Cases

Objective: To observe the therapeutic effects in acupunture treatment of primary dysmenorrhea combined with spinal Tui Na, and study its mechanism. Methods: Thirty cases of the treatment group were treated by acupuncture combined with spinal Tui Na, and thirty cases in the control group were treated by routine acupuncture. Results: The total effective rate was 93.3% in the treatment group, and 73.3% in the control group, with a significant difference between the two groups (P<0.05). Conclusions: Acupuncture combined with spinal Tui Na has good prospects for treatment of primary dysmenorrhea.     

Luo Lingjie's Experience in Treating Chronic Nephropathy

In treating chronic nephropathy,Luo Lingjie,a chief physician,pays attention to regulating the balance between yin and yang,treating infection if present,and removing pathogenic factors.He prescribes gentle drugs and uses carefully strongly warming-tonifying ones,emphasizes the importance of persuading the patient to persist in treatment with medication and nurse one's health for recuperation,and is good at combined use of TCM and western medicine therapy and brings the merits of various therapies into full play,with obvious theraoeutic effects.     

Dr.Zhang Ren's Experience in the Acupuncture Treatment of Different Diseases with the Same Therapeutic Principle

Dr.Zhang Ren,the chief physician,is the chairman of Shanghai Acupuncture and Moxibustion Association.Having been engaged in medicine for about 40 years,he is experienced in treating various intractable diseases.In his long years of clinical practice,he advocates taking the TCM differentiation as the basis to seek for the acupuncture method for treatment of modern intractable diseases.The author of this essay had the fortune to follow Dr.Zhang in study.The following is a summary of Dr.Zhang's experience in the acupuncture treatment for different intractable diseases with the same therapeutic principle.     

安心颗粒对急诊经皮冠状动脉介入术后生活质量影响的研究

目的：评价使用安心颗粒对急诊经皮冠状动脉介入术（PPCI）术后生活质量的影响.方法：将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组（术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次）和对照组（仅接受基础药物治疗）.所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表（MIDAS）、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果：入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异（P＞0.05）;出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低（P＜0.05）;组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低（P＜0.05）.两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血（P＞0.05）.两组发生轻度血小板减少症的患者数比较无差异（P＞0.05）.结论：PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.     

猪肺磷脂注射液联合经鼻持续气道正压通气对呼吸衰竭早产儿的临床疗效及肌酸激酶同工酶活性的影响

目的 探讨猪肺磷脂注射液联合经鼻持续气道正压通气(NCPAP)对呼吸衰竭早产儿的临床疗效及肌酸激酶同工酶活性(CK-MB)的影响.方法 选取呼吸衰竭早产儿80例,分为观察组和对照组各40例.对照组采用NCPAP给氧治疗,观察组给予NCPAP给氧联合猪肺磷脂气管内给药.观察两组患儿治疗前及治疗12h、24 h后PaO2、PaCO2、血氧饱和度(SaO2)、pH的变化情况,检测治疗前及治疗5d后血清CK-MB水平;评估两组患儿的临床治疗效果.结果 两组患儿PaO2、PaCO2、SaO2、pH比较,差异均有统计学意义(P＜0.05),其中观察组治疗后的PaO2、SaO2、pH均高于对照组,PaCO2则低于对照组.两组的PaO2、SaO2、pH均随观察时间延长而升高(P＜0.05),PaCO2均随观察时间的延长而降低(P＜0.05).观察组治疗有效率为87.5％,显著高于对照组的70.0％ (P ＜0.05).治疗5d后两组患儿血清CK-MB水平均较前降低(P＜0.05),且观察组明显低于对照组(P＜0.05).结论 猪肺磷脂注射液气管内给药联合NCPAP可以显著降低呼吸衰竭早产儿CK-MB的含量,提高治疗有效率,起到很好的呼吸循环支持作用.