超高效液相色谱-质谱/质谱联用法测定人血浆中的辛伐他汀

建立了超高效液相色谱-质谱/质谱联用法(UPLC-MS/MS)测定人血浆中辛伐他汀的浓度。血浆样品经乙醚-正己烷-异丙醇(体积比为80∶20∶3)提取,以洛伐他汀为内标,采用ACQUITY UPLCTM BEH C18柱(50 mm×2.1 mm,1.7 μm)分离,以乙腈-10 mmol/L乙酸铵水溶液(体积比为85∶15)为流动相,流速为0.25 mL/min,通过电喷雾离子化,采用多反应监测(MRM)方式进行正离子检测。线性范围为0.051～20.4 ng/mL,日内及日间测定的相对标准偏差不高于10%,平均回收率为91.6%。方法灵敏度高,分析速度快,操作简便,适用于辛伐他汀药物动力学和生物等效性研究。     

高效液相色谱-质谱联用测定胶原蛋白中的羟脯氨酸

建立了一种简单、快速地测定胶原蛋白中羟脯氨酸(HYP)的高效液相色谱-电喷雾质谱(HPLC-ESI/MS)方法。胶原蛋白经酸水解后,以乙腈-0.05%的三氟乙酸水溶液(体积比为5∶95)为流动相,以1.0 mL/min的流速在C8反相柱上进行分离。以茶氨酸为内标,利用质谱定性定量测定HYP。在电喷雾正离子模式下,对m/z 132和m/z 175离子进行选择离子监测。在11.7～117 mg/L范围内,HYP与内标物茶氨酸的峰面积比和HYP的质量浓度呈良好的线性关系,相关系数为0.9993。含量测定的相对标准偏差为1.87%,回收率为97.85%～101.76%。此方法流动相简单,分析时间短且无需衍生处理,抗干扰能力强,能准确快速地测定胶原蛋白中HYP的含量。     

高效液相色谱-串联质谱联用测定人血液中的全氟化合物

采用HPLC-ESI-MS/MS联用技术,建立了分析血样中9种全氟化合物(PFCs)的方法.以13C4标记的PFOS (MPFOS)作为内标物.以C18反相柱为分析柱,甲醇、醋酸铵为梯度洗脱淋洗液,9种分析物包括全氟己烷磺酸(PFHxS)、全氟庚酸(PFHpA)、全氟辛酸 (PFOA)、全氟辛烷磺酸(PFOS)、全氟壬酸(PFNA)、全氟癸酸(PFDA)、全氟十一酸(PFUnDA)、全氟十二酸(PFDoDA)和全氟十四酸(PFTA),在15 min内即可达到良好的分离.在血样前处理中,采用MTBE液-液萃取和固相萃取相结合的方法,进一步净化样品以延长色谱柱寿命;比较了4种固相萃取小柱对全氟化合物的萃取性能,最终选定HLB柱(Waters).本研究还讨论了两种C18反相柱Acclaim 120(50 mm×4.6 mm, 3 μm)和Acclaim120 (250 mm×4.6 mm, 5 μm)(Dionex) 对PFCs的分析性能,在本实验条件下,两种色谱柱具有相似的分离性能及检出限,线性范围在0.1～50 μg/L之间 (r≥0.9957);对于血液样品该方法的检出限在0.03～0.8 μg/L之间.本研究将该方法成功地应用于血样实际样品中全氟化合物的测定,加标回收除PFTA较低外,其它化合物均在74.2%～118.1%之间.     

高效液相色谱-质谱联用技术测定人血浆中的西替利嗪

建立了人血浆中西替利嗪的液相色谱-质谱联用测定方法.血浆样品调至pH 6,经V(乙酸乙酯):V(CH2Cl2)＝4:1液-液提取后,以Agilent Zorbax SB-C18(2.1 mm×150 mm i.d.,3.5 μm)柱为色谱柱,流动相为V(乙腈):V(1%甲酸水)＝55:45溶液,流速为0.5 mL/min,柱温:25 ℃,进样量:5 μL,在Agilent 1100 LC/MSD XCT离子阱质谱仪上,以多重反应离子(MRM)方式进行定量分析,用于监测的离子为m/z 389→201(西替利嗪)和m/z 515→497(替米沙坦,内标物).西替利嗪的检出限为0.50 μg/L(S/N=3),线性范围为2.5～400 μg/L,方法回收率在82.0%～86.7%之间(n=5),精密度与准确度符合生物样品分析要求.该法可用于西替利嗪临床血药浓度和药代动力学研究.     

高效液相色谱-串联质谱联用技术测定环境水样中的全氟化合物

采用HPLC-ESI-MS/MS联用技术,以C18反相柱为分析柱,以甲醇、醋酸铵为淋洗液,10min即可分离全氟庚酸(PFHeA)、全氟辛酸(PFOA)、全氟辛烷磺酸(PFOS)、全氟壬酸(PFNA)和全氟癸酸(PFDeA)5种全氟化合物。样品溶液500mL经RP柱离线浓缩、2mL甲醇洗脱、水定容至5mL后,50μL进样分析。以363/319、412.9/368.9、498.9/80、462.9/419和512.8/469离子对分别对PFHeA,PFOA,PFOS,PFNA和PFDeA进行监控和定量检测。线性范围在0.5~20ng/L之间(r≥0.9944),5种物质的检出限依次为0.10、0.15、0.11、0.11和0.18ng/L。该方法已成功运用于4种环境水样的测定,4ng/L的加标回收结果在52.6%~117.5%之间。     

高效液相色谱-质谱联用技术同时测定人体尿液中11种代谢物

采用高效液相色谱-质谱联用技术定量检测人体尿样中丙烯醛、苯、1,3-丁二烯、苯乙烯、巴豆醛的巯基尿酸类代谢物及氰化氢代谢物。将解冻后的尿样经高速离心后,取100μL上清液,加入50μL内标溶液及850μL水后上样分析。色谱分析采用XSELECT HSS T3 C18色谱柱(150 mm×2.1 mm i.d,2.5μm),以乙腈-15 mmol醋酸铵溶液梯度洗脱,流速250μL/min,柱温40℃,在多反应监测模式(MRM)下采用负离子扫描模式进行定量分析。本方法共检测了16名吸烟者和6名非吸烟者的尿样,发现日吸烟量大于25支的吸烟者尿样中的烟气成分代谢物浓度高于非吸烟者。     

高效液相色谱-质谱/质谱测定血浆中格列苯脲

本文建立了人血浆中格列苯脲的高效液相色谱-质谱/质谱(HPLC-MS/MS)分析方法。血浆中格列苯脲测定的线性范围是1~300 ng/mL;高、中、低三个浓度分析测定的精密度(RSD)<15%;格列苯脲和格列齐特(内标)绝对回收率均>80%。本方法灵敏、准确,重现性好,用于血药浓度的测定获得满意结果。     

高效液相色谱-质谱联用技术的应用进展

高效液相色谱-质谱联用技术具有高分离能力、高灵敏度、应用范围广和极强的专属性等特点。对高效液相色谱-质谱联用技术在药物分析、食品分析和环境分析等领域的应用,特别是在中草药成分分析、中药指纹图谱研究、药物代谢研究、体内药代动力学研究、西药及中成药成分分析、药物筛选研究等方面的应用进行了综述。     

液相萃取-高效液相色谱-串联质谱联用测定污泥中的全氟化合物

全氟化合物是一种新型持久性有机污染物,污水处理厂是其一个主要污染来源。目前还没有建立起一种统一的污泥样品中全氟化合物的分析方法。本文报道了一种基于液相萃取和高效液相色谱-串联质谱联用技术测定污泥中的7种全氟烷基羧酸及其2种不饱和氟调酸前体物、2种全氟烷基磺酸及其5种磺酰胺衍生物前体物的方法。实验对萃取剂(甲醇)的pH值、超声萃取温度与时间、洗脱剂体积进行了优化,确定了中性溶剂、40℃下超声萃取10min,Envicarbon柱净化的前处理方法,并成功地应用于实际污泥样品中全氟化合物的测定。方法的回收率为74%～141%(不饱和氟调酸除外),线性范围为0.1～20μg/L(羧酸系列)及0.25～50μg/L(磺酸系列)内线性关系良好(r20.99),定量限为0.6～30μg/kg(干重)。内标物质的使用可有效消除环境基质引起的仪器离子抑制现象,使定量更加准确。     

高效液相色谱-电感耦合等离子体质谱联用技术测定花茶中砷形态

应用高效液相色谱-电感耦合等离子体质谱(HPLC-ICP-MS)联用技术,建立了花茶中6种砷形态:亚砷酸根、砷酸根、一甲基砷酸、二甲基砷酸、砷胆碱、砷甜菜碱的分析方法。样品在真空条件下采用水-磷酸进行提取,用Hamilton PRP-X100阴离子交换柱,以碳酸铵溶液和硝酸铵+磷酸氢二铵作为流动相进行梯度洗脱,电感耦合等离子体质谱进行定性和定量分析。方法学验证表明:在0.5～50μg/L范围内各砷形态线性良好,线性相关系数(r2)都大于0.999,定量限为0.5μg/L,加标回收率在89.9%～104.1%之间,相对标准偏差(RSD)在1.4%～4.2%之间。方法适用于各类花茶中的6种砷形态分析。     

Simultaneous Determination of Artesunate and Dihydroartemisinin Concentrations in Human Plasma by High Performance Liquid Chromatography-Mass Spectrometry with Electro-Spray Ionization

An analytical procedure was developed/validated for the quantification of artesunate (ARTS) and a metabolite, dihydroartemisinin (DHA), in human plasma. Plasma samples were processed by solid-phase extraction and analyzed by LC-MS. The detector response was specific and linear for ARTS and DHA concentrations in the range of 5–1000 ng/mL. Intra-/inter-day precision/accuracy were determined to be within the acceptance criteria for assay validation guidelines. The analytes were stable under various processing/handling conditions. The ARTS/DHA concentrations were readily measured in plasma samples up to 8 hrs after an oral administration of an ARTS formulation in humans, suggesting that the assay is practically useful.     

Determination of Tropisetron in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry

A fast and sensitive liquid chromatography tandem mass spectrometric method has been developed and validated for the determination of tropisetron in human plasma. The HPLC separation was performed on a Phenomenex Synergi Fusion RP80 column using acetonitrile ?13 mM ammonium acetate – acetic acid (30:70:0.035, v/v) as the isocratic mobile phase. The assay was linear over the concentration range 0.5–128 ng/mL. The intra- and inter-assay precision was less than 11.6% for tropisetron. The method was successfully used to characterize the pharmacokinetic profiles of tropisetron in 20 healthy volunteers after an intravenous infusion of 5 mg tropisetron.     

HPLC-APCIMS联用法测定全血中杀鼠迷

杀鼠迷(coumatetralyl)又称立克命,化学名为4-羟基-3-(1,2,3,4-四氢-1-萘基)香豆素,是一种慢性、广谱、高效、适口性好的第一代抗凝血类鼠药,其结构式如右所示。由于使用不当,造成人和牲畜中毒的事件常有报道[1]。为配合中毒病人的临床诊断与治疗,有必要建立全血中杀鼠迷的快速     

Determination of Captopril in Human Plasma by Liquid Chromatography/Tandem Mass Spectrometry

Abstract

In this study, a fast and sensitive liquid chromatography/tandem mass spectrometry method for the determination of captopril in human plasma was developed and validated. The analyte and enalaprilat, used as the internal standard, were extracted from plasma using methanol directly precipitate protein. Analysis was performed on a Lichrospher CN column with water (containing 0.1% formic acid) and methanol (60∶40, v/v) as the mobile phase. Linearity was assessed from 6.25 to 800 ng/ml in plasma. The analytical method proved to be applicable in a pharmacokinetic study of captopril after oral administration of 20 mg captopril tablet to 20 healthy volunteers.     

液相色谱-串联质谱法测定人血浆中的头孢替安浓度

为评价盐酸头孢替安酯片在健康人体内的药代动力学特征,应用蛋白沉淀-液相色谱-串联质谱技术建立了灵敏度高、特异性强、快速的健康受试者血浆中头孢替安的分析方法。选用 Waters Symmtry C18色谱柱(50 mm×4.6 mm,5μm),以甲醇和1 mmol/ L 乙酸铵水溶液梯度洗脱,流速1.0 mL/ min。在多反应监测模式(MRM)下,采用电喷雾离子化源,正离子扫描模式下进行定量分析。标准曲线在5.0~5000 ng/ mL 范围内线性关系良好(r>0.99),定量下限为5.0 ng/ mL,方法学验证部分结果均符合生物样本定量测定的要求。本方法快速、灵敏、重现性好,并成功应用于健康受试者盐酸头孢替安酯片药动学研究,同时也为同类药物在人体生物基质中的定量检测提供参考。     

Determination of Diazepam in Human Plasma by Solid-Phase Microextraction and Capillary Gas Chromatography-Mass Spectrometry

A simple, sensitive, and reproducible solid-phase microextraction and capillary gas chromatography-mass spectrometry (SPME-GC-MS) method for determination of diazepam in human plasma is described. The optimum conditions for the SPME procedure were as following: direct extraction mode with a polydimethylsiloxane (PDMS) fiber (100 μm film thickness), 250 μL of sample plasma matrix modified with a solution containing sodium chloride (10% weight by volume) and 4.25 mL of a phosphate buffer solution (0.1mol L⁻¹, pH 6.9), extraction temperature 55°C under a magnetic stirring rate of 2500 rpm for 30 min, followed by the drug thermal desorption (250°C) in a GC injection port for 10 min. The limit of quantification of diazepam in plasma was 10.0 ng mL⁻¹, with a coefficient of variation lower than 14.0% and linearity from 10.0 to 1000.0 ng mL⁻¹, which allows diazepam analyses from sub to therapeutic levels.     

Simultaneous Determination of Chloroquine and Its Metabolite Desethyl Chloroquine in Human Plasma Using Liquid Chromatography Tandem Mass Spectrometry

This study presents a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of chloroquine (CQ) and its metabolite desethyl chloroquine (DCQ) in human plasma. The method generally involved methanol protein precipitation and LC-MS/MS detection. The mass spectrometer was operated with positive electrospray ionization (ESI) source and the data acquisition was carried out in multiple reaction monitoring (MRM) mode. Quantification was performed by labeled isotope dilution method with matrix-matched calibration curves. Inter-batch accuracies were ranged from 90.2% to 109.8%. Both intra-batch and inter-batch precisions (relative standard deviation, RSD, %) of the analytes were no more than 15.0%. The recoveries were from 73.7% to 79.0%, and the limit of quantification (LOQ) was 1.0 and 0.5 ng/mL for CQ and DCQ, respectively. The linear ranges of CQ/DCQ were 1.0/0.5–500.0/250.0 ng/mL with the linear correlation coefficient R² > 0.999. No significant matrix effect was observed in this study. The carryover effect was significantly minimized by the addition of ethylene glycol in the reconstitution solution and the utilization of basic washing solution and repetitive fast washing gradient program. After optimization, the carryover effect was less than 20%. This method is in possession of sufficient resolution, high sensitivity as well as selectivity and convenient to be applied to the trace determination of CQ and DCQ in human plasma.     

高效液相色谱-离子阱质谱法测定人血浆中的头孢拉定和青霉素G

目前,β-内酰胺类抗生素在临床抗感染药物中占有十分突出的地位,但在近年来的药品不良反应报告中,抗生素类药物引起的不良反应也占据了很高的比例,其中有我国生活环境影响、感染性疾病多的客观因素,但病人用药盲目性大、医生用药随意性多的问题也普遍存在。因此,进一步加强对抗生素类药物的监测,开发快速有效的分析测试方法显得十分重要。本文基于实际全血未知样品,开发了基于固相萃取及液质联用技术,快速准确地对血液中青霉素G及头孢拉定进行定性及质谱定量分析的检测方法。     

高效液相色谱法测定血浆中米非司酮

建立了测定血浆中米非司酮浓度的高效液相色谱分析方法。血浆样品以乙醚提取,常温下负压挥发至干,所得残渣用甲醇浸溶后进行测定。Spherisorb C18(250 mm×4.6 mmi.d.,5μm)为色谱柱,流动相为甲醇-乙腈-水(50 25 25)溶液,检测波长为302 nm,用外标法定量。结果表明,在0.05~10.00 mg.L-1范围内呈线性,检出限为0.01 mg.L-1;平均回收率为98.2%,日内、日间平均精密度分别为7.0%,8.3%。米非司酮血浆样品的萃后残渣于-20℃可保存至少7d。     

液相色谱-串联质谱法测定人血浆中卡托普利的浓度

建立了测定人血浆中卡托普利的LC/MS/MS法。取血浆0.2 mL,用对溴苯甲酰甲基溴进行衍生化,经甲醇沉淀蛋白后,以甲醇-10 mmol/L乙酸铵-甲酸(80/20/0.4,V/V)为流动相,用Zorbax SB-C18柱分离,通过配有电喷雾离子化源的四极杆-线性离子阱质谱仪,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/z416→m/z216(卡托普利衍生物)和m/z28→m/z193(安定)。卡托普利的线性范围为2.5~1000μg/L,最低定量限为2.5μg/L,样品分析时间为2.0 m in。该法精密、准确,在灵敏度和分析速度上优于以往文献报道,适用于游离型卡托普利血药浓度的监测和药动学研究。