LC-MS/MS法定量测定人血浆中普罗布考的浓度

目的：建立一种特异、灵敏的液质联用方法定量测定人体血浆中普罗布考的浓度。方法：在25.0μL含待测药物的血浆中加入内标Pr-1312及萃取液混匀沉淀蛋白。采用X-Terra RPC（82.1mm×50mm,3.5μm）色谱柱;柱温50℃;流动相为10mmol·L-1碳酸氢铵水溶液-乙腈（20：80）;进样量5μL;流速0.2mL·min-1。质谱检测方式为ESI-,MRM扫描,监测普罗布考m/z515.3→236.1,内标Pr-1312m/z382.2→161.0,分析时间3.3min。结果：普罗布考在10.0～5000.0ng·mL-1的浓度范围内线性关系良好（r〉0.99）,日内与日间精密度（RSD）〈10.2%,准确度（RE）〈±15.0%。所有稳定性考察项目结果均符合要求。结论：本文采用蛋白沉淀样品前处理以及液质联用定量测定人体血浆中普罗布考的浓度方法,能够满足临床试验中生物样品分析的需要。     

LC-ESI-MS/MS快速测定人血浆中匹伐他汀浓度

目的建立一种快速灵敏测定人体血浆中匹伐他汀浓度的高效液相色谱串联质谱检测方法。方法以AgilentC18柱（4.6mm×150mm,3.5μm）为色谱柱,流动相为甲醇-0.005mol·L^-1甲酸铵水溶液-乙腈-1%甲酸水溶液（7.5∶2.5∶70∶20）;流速：0.5mL·min^-1,柱温：40℃。采用选择反应监测（SRM）对匹伐他汀（m/z422.2→290.2）和内标瑞舒伐他汀（m/z482.2→258.2）进行测定。结果匹伐他汀高（80μg·L^-1）、中（50μg·L^-1）、低（0.25μg·L^-1）3个浓度的平均回收率RSD均小于15%;线性范围为：0.1-100μg·L^-1,回归方程为Y=1.2226X-1.0561×10^-4,r=0.9960。结论该方法灵敏、准确、简单、快速,可用于匹伐他汀临床血药浓度监测和药动学研究。     

高效液相色谱串联质谱法测定人血浆中氨溴索浓度

目的：建立测定人血浆中氨溴索浓度的高效液相色谱串联质谱法,以用于氨溴索人体药动学研究。方法：以西替利嗪为内标,血浆样品经乙腈沉淀后,经HPLC—MS／MS分离-分析。采用Waters ODS C18柱（50mm×2．1mm,3．5μm）,以甲醇：5mmol·L^-1乙酸铵（72．5：27．5）为流动相,流速：0．20ml·min^-1,采用电喷雾离子源（ESI）,以多离子反应监测方式（MRM）进行正离子监测,氨溴索和内标西替利嗪的定量分析离子对分别为m／z 379．0→263．9和m／z 389．1→201．3。结果：氨溴索血浆浓度测定方法线性范围为1．99～398ng·ml^-1,r=0．9990。定量下限为1．99ng·ml^-1,方法回收率在85％～115％之间。日内和日间RSD〈15％。结论：本法灵敏、准确、可靠,适用于盐酸氨溴索人体药动学研究。     

HPLC-MS/MS法测定大鼠血浆中金丝桃素的浓度

目的：建立HPLC-MS/MS法测定大鼠血浆中金丝桃素的浓度。方法：血浆样本加入适量内标,经乙腈直接沉淀蛋白后采用HPLC-MS/MS进行分析。色谱柱采用Ultimate C18柱（150 mm×2.1 mm,5.0μm）;流动相由乙腈-5 mmol·L^-1醋酸铵（含0.1%甲酸）（90∶10）组成,柱温35℃;流速0.5 ml·min^-1;采用电喷雾离子源（ESI）,以多反应监测方式（MRM）进行定量分析。金丝桃素和内标吡格列酮在负离子模式下定量分析离子对分别为m/z 503.2→m/z 405.1和m/z 355.0→m/z 41.9。结果：金丝桃素在0.1-13.2 ng·ml^-1线性关系良好（r〉0.99）,最低定量限为0.1 ng·ml^-1,提取回收率为84.19%-98.71%,日内、日间精密度均不高于18.47%。结论：该方法分析速度快、灵敏、准确,为临床进一步研究金丝桃素提供了基础。     

LC-MS／MS法测定人血浆中的帕珠沙星

目的：建立一种快速灵敏检测帕珠沙星血药物浓度的液相色谱－串联质谱方法。方法色谱柱为 Agilent Eclipse XDB－C18（4．6mm ×150mm,5μm）;流动相为乙腈：水（0．005mol· L－1甲酸铵,0．1％甲酸）＝（30∶70）;流速：0．5mL· min －1;质谱条件为电喷雾电离源（ESI）;采用选择反应监测（SRM）对帕珠沙星（m／z 319．0→301．1）和环丙沙星（m／z 332．2→314．2）进行测定。样本处理采用乙腈沉淀蛋白法,吸取上清液1μL进样。结果帕珠沙星的线性范围为0．02～20μg· mL －1,提取回收率为82％～92％,日内和日间精密度均小于15％。结论本方法简便、灵敏,该方法经考察符合血浆样品的测定要求,可以应用于临床药物浓度的测定和药代动力学的研究。     

LC-MS／MS法测定全血中他克莫司浓度的方法学研究

目的：建立测定人全血中他克莫司液相色谱-串联质谱联用（LC-MS／MS）方法,并与微粒子免疫分析（MEIA）方法测定的结果进行了比较。方法：运用LC-MS／MS方法,血样经乙腈沉淀蛋白,上清液氮气吹干流动相复溶进样。色谱柱：Zorbax Extend—C18柱（150mm×4．6mm,5μm）;流动相：甲醇-乙腈-20mmol·L^-1醋酸胺溶液（80：15：5）;流速：0．4ml·min^-1。采用电喷雾离子化四极杆串联质谱,多反应检测方式测定样品的浓度。检测离子对分别为m／z821．7→m／z 768．4和m／z 821．7→m／z 786．5。结果：他克莫司在0．5～128ng·ml^-1浓度范围内,峰面积与浓度线性关系良好（r=0．9991,／2=5）,最低定量限为0．5ng·ml^-1,平均回收率为99．0％,日内精密度、日间精密度的RSD分别为3．38％和4．16％。MEIA分析采用标准IMX测定方法。两种方法比较,其标准差小于3．0,表明相关性好。结论：本方法具有良好的灵敏度、准确度、精确度及专属性,可用于他克莫司血药浓度监测和人体药药动力学研究。     

液-质联用法测定人血浆伊潘立酮的药物浓度

目的:建立高效液相串联质谱方法测定人血浆中伊潘立酮的药物浓度。方法:方法色谱柱为Kromasil 60-5CN(100mm×2.1mm,5μm),流动相:乙腈与5mmol·L-1醋酸铵缓冲液(含0.1%甲酸)体积比为35∶65,流速为0.3mL·min-1,吡格列酮为内标,采用电喷雾离子源,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分别为m/z 427.2→m/z261.2(伊潘立酮),m/z357.2→m/z133.8(吡格列酮,内标)结果:伊潘立酮的血浆浓度在20～20 000pg·mL-1范围内线性良好,定量下限为20pg·mL-1,日内精密度<3%,日间精密度<9%,回收率为96.9%～101%。结论:该法操作简单,灵敏,准确,重现性好,适用于伊潘立酮人体药动学研究及生物等效性研究。     

人血浆中卡巴拉汀及其代谢物NAP226-90的LC-MS/MS测定研究

目的：建立LC-MS/MS法同时检测卡巴拉汀及其代谢物NAP226-90血药浓度。方法：血浆经甲基叔丁基醚-二氯甲烷提取预处理,用Phenomenex-curocil PFP（250 mm×4.6 mm,5μm）色谱柱,0.1%甲酸0.05%甲酸铵溶液-0.1%甲酸0.05%甲酸铵甲醇为流动相,梯度洗脱分离,ESI正离子化三重四极杆质谱MRM测定,检测反应离子对：卡巴拉汀m/z 251.0→206.0、NAP226-90 m/z 166.0→121.0、内标（美托洛尔）m/z 268.4→74.3。结果：卡巴拉汀及NAP226-90血药浓度在0.2～30 ng·mL-1范围内均线性关系良好,定量下限均为0.2 ng·mL-1,经方法学验证符合生物样品测定要求。结论：建立的LC-MS/MS方法可用于重酒石酸卡巴拉汀胶囊人体药动学研究。     

LC-MS/MS法测定小鼠血浆中帕唑帕尼的浓度

目的:建立快速、灵敏的LC-MS/MS法测定小鼠血浆中帕唑帕尼的浓度。方法:以非索非那定为内标,血浆样品经乙腈沉淀。采用Agilent Zorbax C₁₈色谱柱（2.1 mm×100 mm,3.5μm）,柱温30℃,流动相为乙腈-水（含0.1%甲酸）（75:25）,流速为0.2 m1·min^-1。质谱条件为电喷雾离子源（ESI源）,正离子模式多反应（MRM）扫描,离子选择通道分别为m/z438.4→m/z 357.7（帕唑帕尼）和m/z 502.1→m/z 466.1（非索非那定）。结果:帕唑帕尼浓度在5～10 000 ng·ml^-1范围内与峰面积线性关系良好（r=0.999 3）,日内及日间精密度（RSD）均小于7.31%,帕唑帕尼绝对回收率为64.82%～71.52%,相对回收率为102.98%～108.14%。帕唑帕尼在小鼠体内的主要药动学参数AUC_0-8、C_max、t_1/2分别为（11 367.8±139.5）ng·h·ml^-1、（5 911.2±100.1）ng·ml^-1、（1.1±0.006）h。结论:该方法快速、灵敏、准确,可用于小鼠血浆中帕唑帕尼的浓度测定。     

液相色谱-串联质谱法测定人血浆中盐酸舍曲林浓度

目的：建立测定人血浆中盐酸舍曲林浓度的液相色谱-串联质谱法。方法：以替米沙坦为内标,内标法定量。流动相：乙腈-10mmol·L^-1乙酸铵-1%甲酸（70：30：0.1）;质谱采用离子喷雾离子化源,扫描方式为多重反应监测（MRM）,用于定量分析的离子反应分别为m/z306.3→m/z159.1（舍曲林）和m/z515.2→m/z276.1（替米沙坦）。结果：舍曲林和替米沙坦的保留时间分别为2.22min和2.44min;舍曲林的线性范围为0.5～50.0ng·mL^-1,r=0.9992,回归方程：Y=0.0021＋0.0217X,最低检测浓度为0.5ng·mL^-1;提取回收率在82%～90%范围内;日内相对标准差〈4%,日间精密度〈13%。结论：此法适合人体血浆盐酸舍曲林浓度的监测及生物利用度研究,结果准确、可靠。     

Role of the liver in the disposition of intravenous nitroglycerin in the rat

Previous studies have indicated that the liver is the main site of nitroglycerin (NTG) elimination when the drug is systematically infused. To examine this hypothesis, we measured the apparent systemic clearance (Cls) of nitroglycerin in anesthesized rats receiving a constant intravenous infusion at a dose of 100 micrograms per kg per min. Animals were divided into shunt and sham groups; the former had undergone a portal vein ligation 10 days prior to the study, while the latter was subjected to a sham operation. On the study day, half of the animals of each group also received probenecid at 200 mg/kg, i.v., a drug previously reported to inhibit organic nitrate ester reductase (ONER) activity in rat liver. Arterial NTG samples were obtained at 41, 43 and 45 min of infusion in all four experimental groups; Cls was 439 +/- 32 ml per kg per min (mean +/- S.E.) in sham, 460 +/- 44 in sham and probenecid, 477 +/- 39 in shunt, and 461 +/- 34 in shunt and probenecid animals. During NTG infusion, hepatic blood flow (measured with a constant infusion of indocyanine green) was decreased markedly in shunted rats as was liver/body weight, indicating hepatic atrophy. The specific activity of hepatic ONER was similar in all four groups. In spite of marked differences in hepatic blood flow and hepatic mass, the Cls was similar in all four groups. The liver does not appear to be a major site for the elimination of systemic nitroglycerin as hitherto assumed.     

HACCP在学校集体食堂卫生管理中的应用研究

目的 通过HACCP在学校集体食堂管理中的应用,提高食品卫生水平,保障学生的身体健康。方法 HACCP原则。结果 食品卫生达到较高水平,极大地减少了食物中毒的发生。结论 提示HACCP原则可在学校集体食堂的卫生管理中发挥有效作用。     

半导体激光治疗老年人压疮疗效观察

目的探讨半导体激光局部照射治疗老年人压疮疗效.方法:收集2012年1月-2015年6月48例压疮患者,分为半导体组和常规组各24例.常规组采用常规治疗,半导体组采用半导体激光加常规治疗,10 d为1个疗程,不超过3个疗程.疗程结束后比较两组疗效.结果:半导体组压疮愈显率为83.33％,创面愈合时间为(12.75±5.51)d,常规组分别为54.17％和(19.63±8.65)d,组间差异有统计学意义(P＜0.05),两组均未见不良反应.结论:半导体激光加常规治疗压疮效果肯定,无明显不良反应,且操作简便.     

脑卒中恢复期患者社区综合康复的疗效观察

目的：探讨社区开展康复活动对于脑卒中患者肢体功能康复的影响。方法：选取2014年4至10月参与社区“陈睿健康工作室”康复活动的脑卒中恢复期患者50例作为观察组,选取同期延吉社区卫生服务中心门诊的50例脑卒中恢复期患者作为对照组（进行门诊随访、服药、自我康复）。采用知识、信念、行为（KAP）量表对观察组患者进行问卷调查。采用简化Fugl-Meyer肢体运动功能评分表（Fugl-Meyer assessment of motor function,FAM）比较两组患者入组时和入组6个月时的肢体功能恢复情况及对家庭医生（门诊医师）的满意度。结果：入组6个月时,两组患者的FAM均有所改善,观察组FAM得分[上肢（50.92±7.05）分,下肢（33.01±1.37）分]较对照组[上肢（34.85±6.55）分,下肢（25.20±4.88）分]更高,差异有统计学意义（t上肢=11.8215,t下肢=10.8595,P均＜0.01）。观察组患者的满意率为92%（46/50）,明显高于对照组的30%（15/50,P＜0.05）。结论：在社区开展康复活动可以促进脑卒中患者肢体功能的康复,提高患者的满意度。     

Evaluation of the safety of enalapril in the treatment of heart failure in the very old

Summary We have introduced enalapril, in doses equal to or less than the 2.5 mg currently recommended, as an adjuvant to digoxin and diuretics in 17 patients of mean (SD) age 83 (5) years with severe heart failure. Only eleven patients tolerated its introduction. Unlike those reported in younger patients, all but one of the adverse drug reactions occurred 8 h or more after the first dose. Aged patients started on ACE inhibitors should be observed in hospital until stabilized on a maintenance dose. Three patients had an adverse reaction which differed in nature from those previously reported: acute confusional state, ataxia and mesenteric ischaemia.Ten patients were discharged on 5 mg or 10 mg maintenance doses of enalapril. In nine of them improvement on triple therapy was sustained for a minimum of three months. ACE inhibition was lost in the other patient when her compliance with enalapril therapy fell to around 75%: monitoring compliance is essential when ACE inhibitors are used in low dosages.Enalapril was withdrawn during follow up in three patients because of symptoms of mesenteric ischaemia and in four because of dramatic deterioration of renal function. One of the latter was found subsequently to have severe bilateral atheromatous renal artery stenosis. When isosorbide dinitrate was substituted for enalapril, symptoms of mesenteric ischaemia resolved and renal function returned to baseline. Continuing surveillance for adverse effects is essential in patients of this age group with severe heart failure, and the risk of occult renal artery stenosis requires regular biochemical screening during follow up.The benefit to cost ratio of ACE inhibitors might be improved in aged patients by their use at an earlier stage in the natural history of heart failure, when perfusion of essential organs is not grossly impaired, but carefully monitored trials would be necessary to establish this.     

替普瑞酮治疗老年慢性浅表性胃炎的疗效分析

目的分析替普瑞酮治疗老年慢性浅表性胃炎的疗效。方法100例老年慢性浅表性胃炎患者,通过计算机随机表数字法分为对照组和实验组,每组50例。对照组患者选择西咪替丁作为本次治疗药物,实验组患者选择替普瑞酮作为本次治疗药物。比较两组患者临床疗效、不良反应发生情况以及生活质量。结果实验组治疗总有效率92.00%高于对照组的76.00%,差异具有统计学意义(P<0.05)。实验组不良反应发生率6.00%低于对照组的20.00%,差异具有统计学意义(χ^2=4.332,P=0.037<0.05)。实验组患者治疗后的生活质量评分(68.68±4.11)分高于对照组的(57.73±3.48)分,差异具有统计学意义(t=14.377,P=0.000<0.05)。结论对于老年慢性浅表性胃炎疾病患者,选择替普瑞酮进行治疗不仅疗效更为理想,而且还不易增加患者的用药不良反应,有利于提高患者的生活质量,建议进一步推广。     

Nifedipine in the treatment of hypertension in the elderly

The effect of nifedipine monotherapy, retard tablets, 20 mg bid, was evaluated in 23 hypertensive patients, mean age, 79 +/- 2 years. Twenty-one patients completed an eight-week study. Blood pressure (BP) decreased to 160/90 mm Hg in 15 patients; in four additional patients diastolic BP dropped by 15% to 28%. In a subset of five patients with isolated systolic hypertension, a significant reduction in systolic BP was noted. Side effects were relatively mild and only two patients discontinued the study. The results suggest that nifedipine monotherapy offers an alternative, logic, therapeutic approach to hypertension in the elderly.     

Interactions among the cannabinoids in the antagonism of the abdominal constriction response in the mouse

The ability of ⁹-tetrahydrocannabinol (THC), cannabinol (CBN), cannabidiol (CBD), 11-OH THC and 8,11-diOH THC to antagonise the abdominal constriction response in the mouse induced by formic acid, phenylquinone, 5-hydroxytryptamine, prostaglandin E₁ (PGE₁) and bradykinin was tested. THC was an effective antagonist against all nociceptive agents with an ED₅₀ in all cases between 1.0 and 2.6 mg/kg. CBN, while also effective against all nociceptive agents, was less potent than THC, with an ED₅₀ range between 46.2 and 112.5 mg/kg. CBD in doses as high as 200 mg/kg was without effect. Using PGE₁ as the nociceptive agent, 11-OH THC was equipotent to THC while 8,11-diOH THC was inactive. Naloxone, while able to antagonise the antinociceptive effect of morphine against formic acid-induced writhing, did not reverse the antinociceptive effects of THC. There were no pharmacological interactions between THC, CBD and CBN.     

Variation in the use of biologics in the management of rheumatoid arthritis across the UK

Abstract

Objectives:

Treatment options for rheumatoid arthritis (RA) include conventional synthetic disease-modifying antirheumatic drugs (sDMARDs) and newer biologic DMARDs (biologics). This study describes treatment patterns, adherence to guidance and outcomes at hospital/regional level in the UK.