目的:评价高脂餐对中国健康受试者单次口服DDO-3055片药动学(PK)和药效学(PD)的影响.方法:采用随机、开放、两阶段双交叉试验设计.筛选合格的健康男性受试者14例,随机分成A,B两组,每组各7例受试者.试验分成2个阶段,第1阶段:A组受试者于d 1高脂餐后给药,B组受试者于d 1空腹给药.第2阶段:A组受试者于d 7空腹给药,B组受试者于d 7高脂餐后给药.两阶段均采用单次口服给药,给药剂量均为200 mg.受试者在每一阶段给药前60 min内和给药后0.5,1,1.5,2,2.5,3,4,6,8,12,24和48 h进行PK血样采集,在每一阶段给药前60 min内和给药后4,8,12,24和48 h进行PD血样采集.结果:入组的14例健康男性受试者均完成本研究.血浆中DDO-3055的峰浓度(Cmax),0-t时间的血药浓度-时间曲线下面积(AUC0-t),AUC0-∞的几何均值比(高脂餐/空腹)分别为77.9％,95.0％,95.0％,其比值的90％CI分别为67.6％ ～89.7％,85.9～105％,85.9％ ～105％.与空腹相比,高脂餐后血浆DDO-3055的Cmax降低22.1％,AUC0-t和AUC0-∞均降低5.0％.与空腹给药相比,高脂餐后血清平均内源性促红素(EPO)最大值与空腹给药相比略有增加,分别为15.015和14.739 mIU·mL-1;餐后平均EPO最大值较基线变化百分比与空腹给药相比有所增加,分别为92.976％和72.796％.本研究未发生不良事件、严重不良事件.结论:高脂餐饮食对健康男性受试者单次口服DDO-3055片的AUC0-t和AUC0-∞无影响,Cmax降低,说明食物对DDO-3055片的吸收速度有一定影响,但影响较弱.

目的 评价中国健康志愿者单次静脉注射低、中、高3个负荷剂量的盐酸尼非卡兰的安全性及QT间期等药效学指标的变化.方法 用随机双盲、安慰剂对照、剂量爬坡临床试验.低、中、高(0.15,0.30和0.50 mg·kg-1)3个剂量试验组,每组纳入14例受试者,每组中各有12名受试者给予试验药物,各组另外2名受试者给予安慰剂.根据体重计算给药量,药物溶于0.9％NaCl,配制为含2 mg·mL-1盐酸尼非卡兰的液体,注射泵5 min匀速注射给药.评价4组受试者给药前后QT间期、PR间期、QRS间期、RR间期、QTc间期指标的变化.结果 低、中、高剂量试验组和安慰剂组受试者用药后血压无明显变化,低剂量试验组心率较基线无明显变化,中、高剂量试验组心率较基线略有下降,部分时间点心率的平均值低于60次/分,均在给药后24 h回复至基线水平.低、中、高剂量试验组受试者均于给药结束即刻出现QT间期延长,静注结束后3 min达到峰值,分别为(450.33±22.25),(476.33±59.30)和(524.31±55.80)ms,QTc间期的变化趋势同QT间期.安慰剂组的QT间期、QTc间期均无明显变化.低、中、高剂量试验组及安慰剂组各时间点PR间期、QRS间期无明显变化.低、中、高剂量试验组受试者RR间期在负荷给药结束即刻至静注结束3 min出现延长,在静脉注射结束3 min至4 h稳定;RR间期在静脉结束后4～6 h较基线明显下降,6～10 h逐渐恢复至基线,10～12 h较基线下降.安慰剂组RR间期的变化趋势同试验组.低、中、高剂量试验组和安慰剂组受试者用药后均无不适主诉.本研究无严重不良事件.结论 在0.15～0.50 mg·kg-1剂量内,受试者单次静脉给予负荷剂量盐酸尼非卡兰的安全性好,盐酸尼非卡兰抗心律失常的药效学指标QT间期延长具有剂量依赖性.

Objective: To analyze the clinical characteristics and risk factors of non-operative acute upper gastrointestinal hemorrhage in patients with adenocarcinoma of the esophagogastric junction. Methods: The clinical diagnosis and treatment data of patients with adenocarcinoma of esophagogastric junction with non-operative acute upper gastrointestinal hemorrhage admitted to Cancer Hospital of Chinese Academy of Medical Sciences from 2004 to 2018 were collected retrospectively, and the survival of patients was followed up by telephone. SPSS software was used for database establishment and analysis. Cox proportional-hazards model was applied to analyse the survival and related risk factors. Results: A total of 70 patients were included in this study, with a median age of 65 (20-81 years). The ratio of male to female is 2.18∶1. There were 36 cases of Siewert type Ⅱ (51.4%) and 34 cases of Siewert type Ⅲ (48.6%). The lymph node metastasis rates of Siewert Ⅱ and Siewert Ⅲ were 75.0% and 94.1%, respectively (P=0.028). The median overall survival time (OS) of all 70 patients was 11.6 months. The median OS of Siewert Ⅱ and Siewert Ⅲ were 20.0 months and 8.5 months, respectively, and the 1-year survival rates were 42% and 9%, respectively (P=0.027). The median OS of M0 and M1 patients were 19.1 and 7.7 months, respectively, and the 1-year survival rates were 40% and 4%, respectively (P=0.049). The median OS of the treatment of operation+chemotherapy, chemotherapy or best supportive care after hemorrhage were 60.0, 22.2, and 7.9 months, respectively, and the 1-year survival rates were 89%, 45%, and 2%, respectively (all P<0.05). Multivariate analysis showed that Siewert Ⅲ (HR=1.965, 95%CI: 1.078-3.583), M1 stage (HR=1.787, 95%CI: 1.002-3.187) and operation+chemotherapy treatment after hemorrhage (HR=0.132, 95%CI:0.032-0.552) were independent prognostic factors for patients of esophagogastric junction adenocarcinoma with non-operative acute upper gastrointestinal hemorrhage. Conclusions: The survival of patients of esophageal gastric junction adenocarcinoma with non-operative acute upper gastrointestinal hemorrhage is poor, especially for patients of Siewert Ⅲ and the late stage. Active operation and chemotherapy after bleeding may positively affect the survival of these patients.

目的 本研究拟通过分析触珠蛋白-CD163-氧应激诱导型血红素加氧酶1(Hp-CD163-HO-1)通路主要基因的交互作用,探索其与2型糖尿病(T2DM)患者冠状动脉粥样硬化性心脏病(冠心病,CAD)发生及病变复杂程度的关联.方法 入选2010年至2015年于阜外心血管病医院行冠状动脉(冠脉)造影检查的T2DM患者共573例,依据造影检查结果分为T2DM+CAD组(n=301)及T2DM-CAD组(n=272);选取T2DM+CAD组中未合并既往事件、经皮冠脉介入治疗、或行冠脉搭桥术的病例作为SYNTAX组(n=131),应用生物信息学筛选通路tagSNPs,以二次PCR及qRT-PCR法进行基因型检测,使用Plink软件及广义多因子降维法统计方法分析tagSNPs及其交互作用在T2DM患者中与CAD发生风险及病变复杂程度的关联.结果 CD163 rs11054072 GA型、白介素4(IL-4)rs3756074 TT型及氧应激诱导型血红素加氧酶1(HMOX1)rs743811 TT型与T2DM患者CAD风险相关;HMOX1 rs743811 TC型及干扰素-γ(IFN-γ)rs2069705 AG型与T2DM合并CAD患者的SYNTAX评分相关.IFNγrs2069705与白介素10(IL-10)rs3790622,白介素6(IL-6)rs1800796、HMOX1 rs743811与IL10 rs1800871分别存在交互作用,并且与T2DM患者冠脉SYNTAX评分相关(P<0.05).结论 Hp-CD163-HO-1通路基因的多态性及交互作用与T2DM患者CAD的发生风险和病变复杂程度有关.

背景心力衰竭,简称心衰,给我国带来了沉重的社会和经济负担.B型利钠肽作为心衰的重要生物标志物,被国内外指南一致作为Ⅰ类推荐.然而,我国B型利钠肽检测在心衰临床诊疗中的应用情况未见报道.目的研究分析2015年我国心衰住院诊疗中在医院水平应用B型利钠肽检测的可及性和检测率.方法 2015年“重大慢病国家注册登记研究—心力衰竭回顾性病历登记研究”(简称China PEACE心衰回顾性病历登记研究)采用分层两阶段随机抽样方法:第一阶段,将全国按经济区域划分为5层,采用简单随机抽样方法确定研究的协作医院;第二阶段,采用系统随机抽样方法,从每家协作医院抽取2015年出院诊断为心衰的住院患者病历.收集协作医院的基本信息,提取心衰患者住院病历信息,分析医院水平B型利钠肽检测的可及性和检测率,规定B型利钠肽检测率≥60％为B型利钠肽医院应用及格.结果 最终纳入188家医院共计15 163份心衰病历.2015年B型利钠肽检测的整体可及性为85.1％ (160/188),各经济地域医院的B型利钠肽检测的整体可及性分布比较,差异有统计学意义(x2=34.3,P＜0.01).多因素Logistic回归分析结果显示,有独立心内科[OR=6.40, 95％CI (1.78, 23.05)]、医院床位数＞300张[OR=4.45,95％CI(1.24,15.95)]是医院水平B型利钠肽检测可及性的影响因素(P＜0.05),同时B型利钠肽在西部农村地区的检测可及性低于东部城市地区[OR=0.37, 95％CI (0.14,0.96),P＜0.05].159家研究的可及医院中B型利钠肽的整体检测率为63.5％(40.0％,82.3％).各经济地域医院的B型利钠肽检测率比较,差异有统计学意义(H=13.19,P=0.01).多因素Logistic回归分析结果显示,有独立心内科[OR=4.91,95％CI(1.53,15.77)]是B型利钠肽医院应用及格的影响因素(P＜0.05).结论 2015年B型利钠肽检测在全国医院水平已基本普及,但就有检测能力的医院而言,在心衰住院患者临床诊疗的检测率有待提高.因此,需要继续推广诊疗指南在临床实践中的应用,特别重视对西部农村地区的资源投入.

目的 比较高效液相色谱-串联质谱法(HPLC-MS/MS)和化学发光微粒子免疫检测技术(CMIA)测定人全血他克莫司(FK506)浓度结果的相关性,以及2种方法在他克莫司浓度监测工作中的应用.方法 收集253例心脏移植患者(n=581)术后服用他克莫司的全血样本,采用HPLC-MS/MS法测定人全血他克莫司血药浓度,通过专属性、标准曲线与定量下限、精密度、准确度、基质效应和提取回收率以及稳定性试验进行方法学验证;并与CMIA法的测定结果进行比较,观察、比较2种检测手段的测定结果及相关性.结果 用HPLC-MS/MS测定人全血他克莫司浓度,线性范围2～30 ng·mL-1,定量下限为2ng· mL-1;日内及日间精密度(RSD％)均小于15％.按照Bland-Altman法计算,95.52％ LoA=(0.22,5.62),95.52％的差值都位于一致限内,两种方法测定值一致性良好.回归方程为FK506 HPLC-MS/MS=0.70×FK506CMIA-0.17,Pearson相关系数为0.902 4(P ＜0.05),说明两种方法具有良好的相关性.结论 HPLC-MS/MS法测定他克莫司血药浓度定量特异性强,灵敏度高.与CMIA法相比,HPLC-MS/MS测定值低,对他克莫司母药有高度的选择性.

Objective: To analyze association of CYP2C19 genotype and platelet function phenotype and their impact on clinical outcomes including bleeding events of coronary artery disease(CAD) patients received clopidogrel post percutaneous coronary intervention(PCI). Methods: Coronary atherosclerotic heart diseases patients underwent elective PCI and coronary stent implantation in Fuwai hospital were prospectively enrolled during May 2012 to April 2013. Patients were assigned into groups by genotype of CYP2C19 (extensive metabolizers, intermediate metabolizers, and poor metabolizers) and phenotype of platelet function (clopidogrel responders, semi-responders, and non-responders). The rates of major adverse cardiovascular events, combined cardiovascular events, and bleeding events were recorded during a at least 12 months follow-up period and compared among above defined groups. The association between genotype or phenotype and clinical outcome was assessed using multivariable Cox regression hazards model. Results: Three hundred and eighty patients received coronary stent implantation and met the inclusion criteria of the study, including 157(41.3%) clopidogrel extensive metabolizers, 176(46.3%) intermediate metabolizers, and 47(12.4%) poor metabolizers according to the genotype grouping; 98(25.8%) were responders to clopidogrel, 149(39.2%) were semi-responders, and 133 (35.0%) were non-responders according to the phenotype grouping. Three hundred and seventy-six patients accomplished follow-up. The highest combined cardiovascular events rate was observed in the poor metabolizers (34.0%(16/47)) as compared to the intermediate metabolizers (19.0%(33/174), P=0.026) and the extensive metabolizers (15.5%(24/155), P=0.005). The highest bleeding events rate was observed in the clopidogrel responders (33.7%(33/98)) as compared to the semi-responders (18.9%(28/149), P=0.008) and non-responders (17.7%(23/130), P=0.008). In multivariable Cox regression analysis, the adjusted risk of cardiovascular death, acute myocardial infarction, stent embolism, target lesion revascularization and angina onset was 2.305 times higher in clopidogrel poor metabolizers than in extensive and semi-metabolizers (95%CI=1.208-4.399, P=0.011). The adjusted HR for bleeding events was 0.540 (95%CI=0.321-0.909, P=0.021) among semi-responders vs. responders, was 0.52 (95%CI=0.301-0.905, P=0.021) among non-responders vs. responders during the 12 months follow-up period. Conclusions: Among CAD patients underwent stenting and clopidogrel treatment, poor CYP2C19 metabolizers group carries a significantly higher risk for combined cardiovascular events than in extensive metabolizers group, while clopidogrel responders patients are at significantly higher risk for bleeding as compared to the semi-responders and non-responders.

Objective To analyze risk factors of liver injury after intravenous administration of amiodarone.Methods Clinical data of 1 919 patients with intravenous administration of amiodarone were analyzed retrospectively;the patients were treated in 5 hospitals in Beijing from June 10,2011 to May 10,2012.According to the occurrence of liver injury after drug administration,patients were divided into liver injury group(185 cases)and normal liver function group(1 734 cases).Gender,age,body mass index,cardiac function,history of alcohol drinking,history of liver diseases,solvent of amiodarone,the loading dose,the total dose during the first 24 h of administration,type of arrhythmia,glomerular filtration rate and drug-related adverse reactions were analyzed.Results In 1 919 patients,370 cases(19.3％) had corrected QT interval(QTc interval) prolongation;185 cases (9.6％) had liver function injury;42 cases(2.2％) had severe hypotension;30 cases(1.6％) had bradyarrhythmia and 14 cases had phlebitis (0.7％).Multivariate logistic regression analysis showed that male was an independent risk factor of liver injury after amiodarone administration (odds ratio =1.805,95％ confidence interval:1.152-2.829,P =0.010);using 5％ glucose solution as the solvent of amiodarone was a protective factor(odds ratio =0.594,95％ confidence interval:0.393-0.898,P =0.013).Conclusions Liver injury and QTc interval prolongation are main adverse effects of intravenous administration of amiodarone.Male is an independent risk factor and using 5％ glucose solution as solvent is a protective factor of amiodarone-induced liver injury.

Objective:To determine the occurrence of amiodarone-induced side effects,and analyze risk factors for amiodarone-induced QTc interval (QT interval corrected by heart rate) prolongation.Methods:Clinical data of 534 in-patients with intravenous amiodarone administration in our hospital from June 10,2011 through May 10,2012 were analyzed retrospectively.According to whether or not the QTc interval prolonged after intravenous amiodarone administration,patients were divided into QTc interval prolongation group(L-QTc) and QTc interval non-prolongation group (N-QTc),then demographic characteristics,medical history,operation,acute kidney injury following cardiac surgery,bonus dose,total dose of amiodarone during the first 24 hours,and types of arrhythmia were compared between two groups,using chi-square or t-student test first and multivariable logistic regression analysis finally.Results:After cases with incomplete ECG records before or after amiodarone administration were picked out,total 243 cases were analyzed.It revealed that 62 patients (25.5％) occurred QTc interval prolongation,18 (5.62％) patients had liver injury,5 patients (2.1％) appeared severe decreased blood pressure,and 2 (0.8％) patients got phlebitis,but nobody had allergic response,bradyarrhythmia or atrioventricular block.Multivariable logistic regression analysis showed that acute kidney injury following cardiac surgery were an independent risk factor for QTc prolongation.Conclusion:Intravenous amiodarone used to be administrated in patients after cardiac surgery in our hospital.Intravenous amiodarone administration induced higher occurrence of QTc interval prolongation.Acute kidney injury following cardiac surgery is an independent risk factor for QTc prolongation.

Purpose The goal of this study was to develop a population pharmacokinetic (PK) and PK/pharmacodynamics (PD) model for ibutilide, to evaluate the time course of its effect on QT interval in Chinese. Methods The population PK and PK/PD model were developed using data from 40 Chinese healthy volunteers using nonlinear mixed-effects modeling, and the final population PK/PD model was applied on 100 patients with atrial fibrillation (AF) and/or atrial flutter (AFL). Findings The PK parameters of ibutilide were best described by a 3-compartment model with first-order elimination. No statistically significant covariate was found for each PK model parameter. Individualized QT interval correction, by heart rate, was performed by a power model, and the circadian rhythm of QT intervals was described by 2 mixed-effect cosine functions. The QT interval data of ibutilide was well characterized by a sigmoid Emax model ( E ( C ) = E m a x γ × C γ / ( EC 50 γ + C γ ) ) with an effect compartment. The final PK/PD model was used to estimate individual parameters of patient data and found good predictions compared with healthy volunteers; AF and/or AFL patients had lower Emax and higher EC50. Implications A population PK and PK/PD model for ibutilide in healthy volunteers was developed and could well capture ibutilide’s PK/PD characteristics. The final PK/PD model was applied on patients with AF and/or AFL successfully.

目的 建立液相色谱-串联质谱法（LC-MS/MS法）测定人血浆中氯胺酮及其代谢物去甲基氯胺酮对映异构体浓度，并用于氯胺酮和右氯胺酮临床药动学研究。 方法 血浆经固相萃取后，采用PLC-MS/MS测定。色谱柱为酸性糖蛋白结合硅胶柱（100 mm×4 mm，5 μm），流动相为异丙醇-10 mmol·L-1醋酸胺溶液（氨水调pH至7.6~7.7）（6：94），流速0.5 mL·min-1，柱温28℃；质谱采用电喷雾离子化（ESI）及多重反应监测（MRM）模式；选择检测离子反应对为m/z 238→m/z 207（R-/S-氯胺酮），m/z 224→m/z 207（R-/S-去甲基氯胺酮），m/z 291→m/z 230（内标甲氧氨苄嘧啶）。 结果 人血浆中氯胺酮对映异构体的线性范围为5~1 000 ng·mL-1，最低定量限为5 ng·mL-1；代谢物去甲基氯胺酮对映异构体的线性范围为2.5~500 ng·mL-1，最低定量限为2.5 ng·mL-1。本方法专属性良好，氯胺酮对映异构体批内批间精密度均小于5%，去甲基氯胺酮对映异构体的批内批间精密度均小于7%。此检测方法应用于全麻腹腔镜手术受试者静脉注射盐酸氯胺酮注射液或盐酸右氯胺酮后的药代动力学研究中。21例患者单次静脉注射消旋体氯胺酮后，R-氯胺酮和S-氯胺酮半衰期分别为（4.06±1.75）h、（3.33±2.23）h；停药后即刻浓度C0~24 h曲线下面积AUC0~24 h分别为（407±91）h·ng·mL-1、（361±87）h·ng·mL-1。代谢物R-N-去甲基氯胺酮和S-N-去甲基氯胺酮半衰期分别为（8.63±2.57）h、（8.73±2.93）h；达峰浓度Cmax分别为（100±22）ng·mL-1、（91±20）ng·mL-1；24 h曲线下面积AUC0~24 h分别为（557±211）h·ng·mL-1、（515±167）h·ng·mL-1。 结论 本方法准确，专属性强，灵敏度高，可满足实际临床研究的需要。

Objective To establish the population pharmacokinetic and pharmacokinetic models of ibutilide in healthy subjects,and to study the dose-exposure-drug effect relationship and variation of ibutilide in healthy subjects and to provide the basis for clinical practice of ibutilide.Methods A total of 40 healthy subjects were enrolled in this single-center,randomized,dose-escalation trial.13 plasma concentrations of ibutilide and 29 QT interval observations were collected from each subject.NONMEM 7.2 was used to establish and evaluate the pharmacokinetic and pharmacodynamic models.Results The pharmacokinetic model of ibutilide was best described by the three-compartment model with linear elimination,and the pharmacodynamic model was rationally characterized by the sigmoid Emax model.Goodness-of-fit (GOF) was validated by visual predictive check(VPC) and Bootstrap,which indicated that the population pharmacokinetic and pharmacodynamic models of ibutilide in healthy subjects were stable and reliable.Parameters with high confidence were obtained,and the individual variation of population pharmacodynamic parameters the exponent of the sigmoid equation (γ) and the maximum response of QT interval (Emax) were 133.50％ and 64.10％,respectively.Conclusion The population pharmacokinetic and pharmacodynamic models of ibutilide in healthy volunteers were established for the first time and the presence of ibutilide-sensitive and poor-response population were observed,which suggested the necessity of individualized administration for ibutilide.

目的：极度右心室肥厚是肥厚型心肌病（HCM）中非常罕见的一种特殊形态，表现为右心室壁的显著肥厚，既往只有散在的病例报告。全基因组测序是最新的二代测序技术，尚未有将全基因组测序用于HCM的研究。本文探究HCM伴有极度右心室肥厚患者的遗传学特点。

Objective:To evaluate the linearity of Coulter automated hematology analyzer LH 780. Methods:The linearity control used to be samples, the linear range of WBC, RBC, Hgb, Plt were evaluated with Coulter original reagents, calibrator and control. Results:The test results of the four parameters showed good linear relationship. The linear range of WBC, RBC, Hgb, Plt were (0.03~363.5)×109 /L, (0.00~7.92)×1012/L, 0.3~236.0 g/L and (0.3~2511.0)×109/L, respectively. Conclusion:For Coulter hematology analyzer LH 780, there is a wide linearity that can meet the demands of clinical laboratories.

目的 探讨冠状动脉造影与支架置入术对腺苷二磷酸(ADP)诱导的血小板聚集率的影响.方法 前瞻性纳入2012年5月1日至2013年4月30日中国医学科学院阜外医院冠心病患者343例,术前至少7d连续服用阿司匹林100 mg,每日1次;氯吡格雷75 mg,每日1次.根据支架置入情况分为单纯冠状动脉造影组(造影组,173例)和支架置入组(170例).患者在接受冠状动脉介入操作之前及之后24 h内,分别采集空腹血样本,用光学比浊法测定血小板聚集率,比较两组患者术前、术后血小板聚集率的变化,支架置入组有66例患者自愿参加血小板聚集率复测亚组分析.结果 两组患者术前、术后血小板聚集率比较,差异无统计学意义(P＞0.05);造影组患者术前、术后血小板聚集率比较,差异无统计学意义(P=0.062),而支架置入组患者术后血小板聚集率显著高于术前[(55.59±10.47)％比(52.47±11.97)％,P＜0.001],差异有统计学意义;支架置入组患者术后血小板聚集率增加大于造影组[(3.12±8.31)％比(1.06±7.40)％,P=0.010],差异有统计学意义.随着患者支架置入数量的增加,术后血小板聚集率呈递增趋势,但差异无统计学意义(P＞0.05).支架置入组血小板聚集率复测亚组患者(66例)术后30 d血小板聚集率显著低于术后24 h[(54.71±11.64)％比(56.68±10.21)％,P=0.019],且与术前基线值比较,差异无统计学意义[(54.71±11.64)％比(54.26±12.23)％,P=0.901].结论 冠状动脉支架置入操作可导致术后血小板活性升高,该作用可在术后30 d内消失,而单纯冠状动脉造影则无此影响.

A liquid chromatography-tandem mass spectrometry (LC-MS) method to quantify tolvaptan and its two main metabolites and applied to human study was first developed and validated as a measure of compliance in clinical research. Because of the structure similarity of tolvaptan and its multiple metabolites, the method was optimized to obtain a chromatographic and MS separation of the endogenous interference and isotope ions as well as high analysis throughput. Tolvaptan, its two main metabolites and the internal standard were extracted from human serum (0.1mL) using solid-phase extraction, separated on a Waters nova-pak C18 column (150×3.9mm, 5μm) using isocratic elution with a mobile phase composed of acetonitrile, water and formic acid (65:35:0.25, v/v/v). The total run-time was shortened to 3.5min. The mass transition ranges under positive electrospray ionisation that were monitored for quantitation included m/z 449-252 for tolvaptan, m/z 479-252 for metabolite DM-4103, m/z 481-252 for metabolite DM-4107 and m/z 463-266 for the internal standard (IS). The limit of quantification in plasma for all three analytes was 1ng/mL. The method was validated over a linear range from 1 to 500ng/mL for all three analytes with acceptable inter- and intra-assay precision and accuracy. The stability of the analytes was determined to be suitable for routine laboratory practices. The method was successfully applied to samples taken from research volunteers who ingested a 15mg tolvaptan tablet.

目的 对ACL TOP 500全自动凝血分析仪进行检测性能评价,包括精密度、准确度和线性范围,并验证参考区间.方法 使用原装配套试剂、校准品和质控品,评价凝血酶原时间(PT)、活化的部分凝血活酶时间(APTr)和纤维蛋白原(FIB)的精密度和准确度,至少20次质控品的检测结果用于评价精密度;20份样本的检测结果与另一台同型号仪器比对用于评价准确度;采用5份样本评价FIB的线性范围;20份健康个体样本用于验证上述3个项目及国际标准化比值(INR)的参考区间.结果 所有项目两水平质控品检测结果的变异系数均＜3.6％;全部样本各项目与同型号仪器的比对结果的差异在总误差范围内;FIB的线性范围为0.52 g/L ～ 7.74 g/L;拟验证的参考区间可接受.结论 ACLTOP 500全自动凝血分析仪的检测性能良好,能满足临床实验室的要求.