Sensitive bioassay for the simultaneous determination of pseudoephedrine and cetirizine in human plasma by liquid-chromatography-ion trap spectrometry

A liquid chromatography-ion trap mass spectrometry coupled with electrospray ionization (HPLC-ESI-ion trap mass spectrometry) method for simultaneous determination of cetirizine and pseudoephedrine in human plasma is presented. Chromatographic separation was performed on a Hypurity C18 column (Thermo Hypersil-Keystone 2.1 mm x 150 mm, 5 microm, USA), The mobile phase was composed of 65% methanol and 35% water (contained 0.1% formic acid, 10 mM ammonium formate), which was run with a flow-rate of 0.2 ml/min at 40 degrees C. Quantitation was achieved by monitoring the product ions at m/z 166-->m/z 148 (pseudoephedrine), m/z 389.9-->m/z 201.1 (cetirizine), m/z 264-->m/z 246 (tramadol, IS). The calibration curve of pseudoephedrine and cetirizine was established with standard solutions. The limit of detection for pseudoephedrine and cetirizine each was 5 ng/ml. This simplified analytical method is sensitive, specific and accurate enough for simultaneous determination of pseudoephedrine and cetirizine in human plasma and is successfully applied to the pharmacokinetic study of pseudoephedrine and cetirizine.     

Determination of omeprazole in human plasma by liquid chromatography-electrospray quadrupole linear ion trap mass spectrometry

An analytical method for the determination of omeprazole in human plasma has been developed based on liquid chromatography mass spectrometry. The analyte and internal standard sildenafil are extracted from plasma by liquid-liquid extraction using diethyl ether:dichloromethane (60:40, v/v) and separated by reversed phase high-performance liquid chromatography (HPLC) using acetonitrile:methanol:10 mM ammonium acetate (37.5:37.5:25, v/v/v) as mobile phase. Detection is carried out by multiple reaction monitoring on a Q TRAP LC/MS/MS system (Q TRAP). The method has a chromatographic run time of 3.5 min and is linear within the range 0.50-800 ng/mL. Intra- and inter-day precision expressed as relative standard deviation ranged from 0.4 to 8.5% and from 1.2 to 6.8%, respectively. Assay expressed as relative error was <5.7%. The method has been applied in a bioequivalence study of two capsule formulations of omeprazole.     

LC/MS/MS法测定人血浆中头孢克肟含量

目的 建立人血浆中头孢克肟的LC/MS/MS法.方法 血浆样品经蛋白沉淀提取,采用C8色谱柱分析,以乙腈:水:甲酸(40:60:0.5,v/v/v)为流动相,三重四级杆质谱检测器,正离子多反应监测模式(MRM),监测离子分别为:m/z 454.3→m/z 285.2(头孢克肟),m/z 282.2→m/z 212.2(...     

The quantitation of procaine in equine plasma by liquid chromatography-linear ion trap mass spectrometry

A method for the extraction and quantitation of procaine in equine plasma was developed for use with liquid chromatography-mass spectrometry (LC-MS). Procaine was isolated from equine plasma by liquid-liquid extraction at pH 11 with dichloromethane using procaine-d10 as an internal standard. Quantitation was achieved by LC-MS using a 3-microm C-18 column coupled to an electrospray ionization source on a linear ion-trap mass spectrometer. The limit of detection and limit of quantitation was determined to be 50 and 200 pg/mL, respectively. The lowest limit of detection determined by previous methods was 1 ng/mL. Administration samples were obtained as part of a larger study to determine a regulatory limit for procaine in racehorses and procaine concentrations were determined using this method.     

Trace quantitation of the novel cholinesterase inhibitor in human plasma by capillary gas chromatography/ion trap mass spectrometry

This paper demonstrates the utility of an ion trap mass spectrometer as a detector for trace quantitative determinations of pharmaceuticals in human plasma by capillary gas chromatography/mass spectrometry. A novel acetylcholinesterase inhibitor (CI-1002) was selected as an illustrative example for the technique. When coupled with a selective solid-phase extraction, this approach was capable of quantifying as little as 34 pg (0.50 ng ml⁻¹, RSD = 12.7%) of compound on the column, and the inter-run precision was typically 3–4% RSD over a 0.5–25 ng ml⁻¹ linear range. The advantages and requirements of the technique, in addition to the propects for improvements in the detection limit, are discussed.     

LC-ESI-MS/MS法测定人血浆中卢帕他定的浓度（英文）

目的建立测定人血浆中卢帕他定浓度的LC-ESI-MS/MS方法。方法血浆样品加入内标,碱化后用二氯甲烷：乙酸乙酯（20：80）提取,在37℃真空干燥箱中干燥至干,残渣用200μL流动相溶解后进样。色谱条件为：色谱柱为Agilent Eclipse XDB-C18（4.6mm×150mm,5μL）;流动相为乙腈（含1%甲酸）：20mmol·L^-1醋酸铵（76：24,V/V）,流速为0.6mL·min^-1。质谱条件：采用美国安捷仑1100高效液相色谱系统和离子阱（Agilent MSD Trap XCT）检测仪,质谱条件为电喷雾离子源,检测方式为正离子电离、多离子反应监测（MRM）,用于定量分析的离子为卢帕他定m/z416→309,内标氯雷他定m/z383→337。结果该方法应用于检测20名健康志愿者服药后的血浆样品。线性范围为0.05～14ng·mL^-1（r=0.998）,日内和日间精密度均低于15%,方法回收率为85.1%～114.0%。最低检测限为0.05ng·mL^-1（当n=5时,RSD=9.22%）。结论该方法灵敏、准确、快速,可用于该药药代动力学和生物等效性研究。     

高效液相-质谱联用测定阿奇霉素的血浆浓度

目的：本实验建立了高效液相质谱联用（HPLGMS／MS）法测定正常人血浆中的阿奇霉素浓度。方法：血浆中加入罗红霉素作为内标，以碱化的醋酸乙酯提取，进行HPLC-MS／MS的测定。采用HanbonLichrospherC18柱（2．1mm&#215;100 mm，5μm），柱温30℃，流动相为乙睛-醋酸铵缓冲液（O．2％醋酸＋0．1％醋酸铵溶液）（60：40），流速0．25mL&#183;min-1；质谱采用选择性离子检测方法。结果：阿奇霉素的线性范围为1．O～1000mg&#183;L-1，最低检测质量浓度为1．0μg&#183;L-1。回收率及精密度的测定均符合生物样品分析的要求。结论：该方法操作简便，灵敏度高，专属性强，可用于测定阿齐霉素的血药浓度。     

HPLC-MS-MS法测定人血浆中托吡酯的浓度

目的:建立测定人血浆中托吡酯浓度的HPLC-MS-MS方法。方法:采用液液萃取法,以甲基叔丁基醚为提取溶剂;HPLC采用Hypersil ODS C18色谱柱(150 mm×4.6 mm,5μm),流动相为5 mmol·L-1醋酸铵溶液-甲醇(25∶75),流速0.5 mL·min-1;质谱采用ESI源,负离子检测模式,定量分析离子为托吡酯m/z338.1[M-H]-→78.0,双氯芬酸钠m/z294.1[M-H]-→249.7。结果:人血浆中托吡酯的标准曲线范围为10.00~3 600.00 ng.mL-1(n=7),r>0.999;日内和日间精密度均小于8.9%;提取回收率(低、中、高)分别为(75.5±3.1)%,(77.0±1.6)%和(72.8±1.5)%,内标提取回收率为(76.1±3.5)%;基质效应(低、中、高)分别为(99.2±5.6)%,(98.9±4.2)%和(99.4±3.8)%,内标基质效应为(100.4±1.3)%。结论:该方法灵敏、快速、专属性强,可用于人血浆中托吡酯浓度的测定。     

液质联用法测定人血浆中米格列奈的浓度

目的建立LC-MS/MS法测定人血浆中米格列奈的浓度,并研究其在健康男性受试者体内的药动学。方法血浆经液-液萃取。色谱柱:Agilent TC-C18柱,流动相:乙腈-水-甲酸(体积比为70.0∶30.0∶0.3),质谱检测采用多反应监测模式(multiple reaction monitoring,MRM),电喷雾离子源,分析时间:2.0 min。结果米格列奈线性为5.0～4 000.0μg.L-1,定量下限为5.0μg.L-1。日内、日间精密度(relative standard deviation,RSD)均不大于10.5%,准确度(relative error,RE)为-0.8%～-2.0%。健康男性受试者口服含米格列奈10 mg的受试制剂(规格:10 mg/片)和参比制剂(规格:5 mg/片)后主要药动学参数为:tmax分别为(0.375±0.079)和(0.396±0.166)h,ρmax分别为(887±292)和(902±298)μg.L-1,t1/2分别为(1.37±0.45)和(1.49±0.57)h,AUC0-t分别为(1047±379)和(1 067±430)μg.h.L-1,AUC0-∞分别为(1 070±394)和(1 092±433)μg.h.L-1。结论该法适用于米格列奈的药动学及生物等效性研究。     

液相色谱-串联质谱法测定人血浆中匹伐他汀

目的:建立灵敏、快速的液相色谱-串联质谱(LC-MS-MS)法测定人血浆中匹伐他汀,并用于药动学研究。方法:血浆样品经乙腈沉淀蛋白后,以乙腈-5 mmol·L~(-1)醋酸铵溶液(90:10,V:V)为流动相,Zorbax XDB C_8柱分离。采用电喷雾电离源(ESI),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 422→m/z 290(匹伐他汀)和m/z 515→m/z 276(内标,替米沙坦)。结果:测定血浆中匹伐他汀的线性范围为0.1～100μg·L~(-1),定量下限为0.1μg·L~(-1)。日内、日间精密度(RSD)均小于12.0%,准确度(RE)在±2.4%以内。结论:该方法选择性好、灵敏度高、操作简便,适用于匹伐他汀的临床药动学研究。     

LC-MS/MS法测定人体血浆中谷氨酰胺的含量

目的建立测定人血浆中谷氨酰胺浓度的液相色谱串联质谱法(LC-MS/MS)。方法血浆样品用质量分数为10%的三氯乙酸沉蛋白,色谱柱:Inertsil-CN柱,流动相:5 mmol·L~(-1)醋酸铵(含体积分数为0.1%的甲酸)-甲醇-乙腈(体积比为70∶15∶15),流速:750μL·min~(-1),质谱:采用多反应检测模式,API2000电喷雾离子源。结果谷氨酰胺的线性为12~384 mg·L~(-1),定量下限为12 mg·L-1,日间日内精密度(relative standard deviation,RSD)均不大于15%。健康男性受试者单剂量口服谷氨酰胺颗粒5 g后的主要药动学参数为:tmax为(0.77±0.13)h,ρmax为(75.3±29.0)mg·L~(-1),t_(1/2)为(1.83±1.93)h,采用梯形法计算,AUC_(0-t)为(109.2±40.1)mg·h·L~(-1),AUC_(0-∞)为(114.0±40.4)mg·h·L~(-1)。结论该法适合于谷氨酰胺颗粒的人体药动学研究。     

液质联用法测定人血浆中沙格雷酯的浓度

目的建立人血浆中沙格雷酯质量浓度的液相色谱-串联质谱(LC-MS/MS)测定方法。方法色谱柱为Elipse XDB-C18柱,流动相为乙腈-0.01 mol·L-1醋酸铵(体积比为65∶35),血浆样品经乙腈沉淀蛋白处理,以选择反应监测(selected reaction monitoring,SRM)扫描方式检测,测定健康男性受试者经口给予盐酸沙格雷酯后血浆中沙格雷酯的质量浓度。结果沙格雷酯线性为5.0¹ 000μg·L-1,定量下限为5.0μg·L-1。日内、日间精密度(Relative Standard Deviation,RSD)均不大于9.0%,准确度(Relative Error,RE)为-6.5%1 000μg·L-1,定量下限为5.0μg·L-1。日内、日间精密度(Relative Standard Deviation,RSD)均不大于9.0%,准确度(Relative Error,RE)为-6.5%².6%。沙格雷酯在健康男性血浆中主要药动学参数tmax为(0.49±0.21)h,ρmax为(725±264)μg·L-1,t1/2为(0.58±0.21)h,AUC0-t为(534±111)μg·h·L-1,AUC0-∞为(540±111)μg·h·L-1。结论该方法适用于沙格雷酯在健康人体内药动学的研究。     

Sensitive determination of buprenorphine and its N-dealkylated metabolite norbuprenorphine in human plasma by liquid chromatography coupled to tandem mass spectrometry

A highly sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the quantitative determination of buprenorphine and its active metabolite norbuprenorphine in human plasma. Automated solid phase extraction (SPE) on disposable extraction cartridges (DEC) is used to isolate the compounds from the biological matrix and to prepare a cleaner sample before injection and analysis in the LC-MS/MS system. After conditioning, the plasma sample (1.0 ml) is loaded on the DEC filled with octyl silica (C8) and washed with water. The analytes are, therefore, eluted by dispensing methanol containing 0.1% of acetic acid. The eluate is collected and evaporated to dryness. The residue is dissolved in mobile phase and an aliquot is injected in the LC-MS/MS system. On-line LC-MS/MS system using atmospheric pressure chemical ionization (APCI) has been developed for the determination of buprenorphine and norbuprenorphine. The separation is obtained on a RP-18 stationary phase using a mobile phase consisting in a mixture of methanol and 50 mM ammonium acetate solution (50:50, v/v). Clonazepam is used as internal standard (IS). The MS/MS ion transitions monitored are m/z 468-->468, 414-->414 and 316-->270 for buprenorphine, norbuprenorphine and clonazepam, respectively. The method was validated regarding recovery, linearity, precision and accuracy. The limits of quantification (LOQs) were around 10 pg/ml for buprenorphine and 50 pg/ml for norbuprenorphine.     

液相色谱-串联质谱法测定人血浆中罗格列酮

目的:建立测定人血浆中罗格列酮的液相色谱-质谱-质谱联用法,并用于临床药动学研究。方法: 血浆样品经液-液萃取后,以乙腈-水-甲酸(90:10:0．5)为流动相,采用Zorbax SB—C18柱分离,通过电喷雾离子化四极杆串联质谱,以选择反应监测(SRM)方式进行检测。用于定量分析的离子反应分别为m／z 358→ 135(罗格列酮)和m／z 256→167(内标苯海拉明)。结果:标准曲线线性范围为0．50～1 000μg·L-1,定量下限为0．50μg·L-1,日内、日间精密度(RSD)均小于7．4％。应用此法测试了20名男性健康受试者口服酒石酸罗格列酮片(相当于罗格列酮4 mg)后血浆中罗格列酮的浓度。结论:该法灵敏、快速、准确,操作简便、线性范围宽,适用于罗格列酮的临床药动学研究。     

Determination of eperisone in human plasma by liquid chromatography-ESI-tandem mass spectrometry

A sensitive and selective method for the determination of 4′-ethyl-3-methyl-3-piperidinopro-piophenone hydrochloride (eperisone hydrochloride) in human plasma was developed and validated. The procedure employed an internal standard and a solvent extraction step followed by chromatography on a Xterra C₁₈ minibore column. Detection was by electrospray ionization tandem mass spectrometry with multiple reaction monitoring. The mass transitions of eperisone and tolperisone (IS) were m/z 260 → 98 and m/z 246 → 98, respectively. The method has a limit of detection of 0.1 pg/mL for eperisone based on the three times signal-to-noise value with a linear range from 0.01 to 10.0 ng/mL for the analyte. Extraction recovery was on average 98.6±7.2% (SD) for eperisone. The Intra- and inter-day assay accuracy ranged from 93 to 114% and precision (RSD) was better than 8.5%. The method was successfully employed to analyze plasma samples and evaluate pharmacokinetics of eperisone in healthy male volunteers.     

液相色谱-串联质谱法测定人血浆中的利培酮

利培酮为苯并异噁唑类化合物,通过阻断5-HT2受体和多巴胺D2受体发挥抗精神病作用.同其他抗精神病药物相比,利培酮所引起的椎体外系副作用更少,药效更为明显 .     

液相色谱-串联质谱法测定人血浆中奥洛他定的浓度

目的建立人血浆中奥洛他定浓度测定的液相色谱-串联质谱（LC—MS／MS）定量方法。方法以地氯雷他定为内标,血浆样品经蛋白沉淀处理后,在0．2mL·min^-1的流速下以乙腈-甲醇-0．1％甲酸水溶液（25：5：70,V／V／V）为流动相进行等度洗脱,采用CAPCELLPAKC18柱（50mm×2．1mm,3．5μm）分离。样品经电喷雾离子源（ESI）正离子化后,通过三重四极杆串联质谱仪,采用多反应离子检测方式测定奥洛他定（m／z338．2／165．2）和内标地氯雷他定（m／z311．1／259．1）的浓度。结果奥洛他定质量浓度在1～200μg·L^-1内线性良好,定量下限为1μg·L^-1,方法回收率为85％-115％,批内、批间RSD均〈10％。结论本方法专属性强、灵敏度高,操作简便、快速,符合生物样品分析要求,适用于临床药动学研究。     

Specific and sensitive analysis of nefopam and its main metabolite desmethyl-nefopam in human plasma by liquid chromatography-ion trap tandem mass spectrometry

A specific and sensitive liquid chromatography–tandem mass spectrometric (LC–MS–MS) method using an ion trap spectrometer was developed for quantitation of nefopam and desmethyl-nefopam in human plasma. Nefopam, desmethyl-nefopam and the internal standard (ethyl loflazepate) were extracted in a single step with diethyl ether from 1 mL of alkalinized plasma. The mobile phase consisted of acetonitrile with 0.1% formic acid (50:50, v:v). It was delivered at a flow-rate of 0.3 mL/min. The effluent was monitored by MS–MS in positive-ion mode. Ionisation was performed using an electrospray ion source operating at 200 °C. Nefopam and desmethyl-nefopam were identified and quantified in full scan MS–MS mode using a homemade MS–MS library. Calibration curves were linear over the concentration range of 0.78–100 ng/mL with determination coefficients >0.996. This method was fast (total run time < 6 min), accurate (bias < 12.5%), and reproducible (intra- and inter-assay precision < 17.5%) with a quantitation limit of 0.78 ng/mL. The high specificity and sensitivity achieved by this method allowed the determination of nefopam and desmethyl-nefopam plasma levels in patients following either intermittent or continuous intravenous administration of nefopam.     

液-质联用测定人血浆中罗红霉素浓度

目的:建立高效液相色谱-质谱联用法测定人血浆中罗红霉素浓度。方法:以克拉霉素为内标,血浆样品经乙腈沉淀后,经HPLC-MS/MS分离分析。采用Waters ODS C18柱(2.1mm×50mm,3.5μm),以甲醇-5mmol.L-1醋酸铵(含0.03%甲酸)(55∶45)为流动相;流速:0.2mL.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,罗红霉素和内标克拉霉素的定量分析离子对分别为m/z837.5→679.4和m/z748.5→590.3。结果:罗红霉素血浆浓度测定方法线性范围为0.02025~13.500mg.L-1,r=0.999 0。定量下限为0.02025mg.L-1,方法回收率在85%~115%之间。日内和日间RSD均小于15%。结论:本试验所建立的方法灵敏、准确、可靠,适于罗红霉素的人体内药动学研究。