液相色谱-串联质谱法测定大鼠血浆中舒巴坦的浓度及其药动学研究

目的：建立测定大鼠血浆中舒巴坦血药浓度的液相色谱-串联质谱（LC-MS/MS）法,探讨美罗培南、亚胺培南对舒巴坦在大鼠体内的药动学影响。方法：将18只SD大鼠随机分为舒巴坦组、美罗培南+舒巴坦组和亚胺培南+舒巴坦组,分别静脉注射给药,按规定时间点采血,血浆样品经乙酸乙酯萃取,LC-MS/MS法测定血药浓度;采用负离子模式,多重反应监测（multiple reaction monitoring,MRM）,定量离子对为m/z 232.3→m/z 139.9（舒巴坦）和m/z 423.4→m/z 207.1（头孢呋辛,内标）。经DAS 2.0.1计算药动学参数,并进行统计学比较。结果：舒巴坦在0.250~200 μg·mL^-1范围内线性关系良好,方法学符合要求。药动学试验结果表明,合用美罗培南或亚胺培南后,舒巴坦在大鼠体内的主要药动学参数t_max、C_max、AUC、MRT、t_1/2z、CL_z和V_z与单用舒巴坦相比,无显著性差异。结论：和已报道的方法比较,本研究所建方法具有快速、高效,生物样品用量小的特点,适用于舒巴坦在大鼠体内药动学的研究;美罗培南、亚胺培南对舒巴坦在大鼠体内的药动学过程无明显影响,提示评价此类药物相互作用还需同时考虑药效学等方法。     

Simultaneous determination of tanshinones and polyphenolics in rat plasma by UPLC‐MS/MS and its application to the pharmacokinetic interaction between them

The aim of this study was to investigate the pharmacokinetic interaction between tanshinones and polyphenolics which act as the main bioactive compounds in Saliva miltiorrhiza Bunge (SMB). Thus, a rapid and highly sensitive ultra‐performance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS) method was developed and validated to determine the concentrations of Tanshinone IIA (TSIIA), Tanshinone I (TI), Cryptotanshinone (CT), Salvianolic acid B (Sal B), Protocatechuic aldehyde (PAL), Rosmarinic acid (RA), and Danshensu (DSS) in rat plasma. The Sprague–Dawley rats were allocated to three groups which orally administered tanshinones (DST), polyphenolics (DFS), and a mixture of tanshinones and polyphenolics (DTF). These samples were processed by a simple liquid‐liquid extraction (LLE) method with ethyl acetate. Chromatographic separation was achieved on an Acquity BEH C₁₈ column (100 mm × 2. 1 mm, 1.7 µm) with the mobile phase consisting of 0.1% (v/v) formic acid and acetonitrile by gradient elution at a flow rate of 0.4 mL/min. The detection was performed on a triple quadrupole‐tandem mass spectrometer TQ‐MS/MS equipped with negative and positive electrospray ionization (ESI) interface in multiple reaction monitoring (MRM) mode. The statistical analysis was performed by the Student's t‐test with P ≤ 0.05 as the level of significance. The method showed good precision, accuracy, recovery, sensitivity, linearity, and stability. The pharmacokinetic profiles and parameters of these polyphenolics changed when co‐administrated with tanshinones. The tanshinones improved the bioavailability of DSS, accelerated the eliminating rate of RA and Sal B and promoted their distribution in vivo. They also contributed to promoting the biotransformation of Sal B to DSS. The polyphenolics could affect the pharmacokinetic of tanshinones, especially CT and TSIIA. Furthermore, the biotransformation of CT to TSIIA and the bioavailability of TSIIA were both improved. This study may provide useful information to avoid unexpected increase of the plasma drug concentration in the clinical practice. Copyright © 2015 John Wiley & Sons, Ltd.     

LC-MS/MS法测定人血浆中加巴喷丁的浓度及其药动学研究

建立液相色谱串联质谱(LC-MS/MS)法测定人血浆中加巴喷丁的浓度并将其应用于人体药动学研究。取血浆样品经甲醇沉淀蛋白后,以甲醇0.2%甲酸水溶液(80∶20)为流动相,用Inertsil ODS-3 C18柱(50 mm×2.1 mm ID,3μm)分离,采用电喷雾离子源,以多反应监测(MRM)方式进行正离子检测,定量分析的离子反应分别为m/z 172→m/z 154(加巴喷丁)和m/z 130→m/z 71(内标二甲双胍)。加巴喷丁线性范围为40.8～8.16×103 ng.mL 1,定量限为40.8 ng.mL 1,每个样品测试时间仅2.2 min,日内、日间精密度(RSD)均小于12%,准确度(RE)在±6.4%范围内。应用此法研究了20名健康志愿者单剂量口服加巴喷丁胶囊600 mg后的药动学特点。该方法快速、专属、灵敏、适用性强,可应用于加巴喷丁的人体药动学研究。     

艾司奥美拉唑UPLC-MS/MS测定方法建立及其在健康中国人中的生物等效性研究

目的 建立UPLC-MS/MS法测定人血浆中艾司奥美拉唑浓度,并应用于人体生物等效性研究。方法 采用UPLCMS/MS法,以艾司奥美拉唑-d3为内标,ACE 3 C₁₈-AR （50 mm×2.1 mm,3 μm）为分析柱,流动相A为5 mmol·L^-1乙酸铵水溶液,流动相B为乙腈,体积流量为0.6 mL·min-1进行梯度洗脱;采用电喷雾离子源,以多反应监测（MRM）正离子模式进行检测,用于定量分析的离子对为m/z 346.1→198.1（艾司奥美拉唑）、m/z 349.1→198.1（艾司奥美拉唑-d3）。应用建立的方法测定人血浆中艾司奥美拉唑浓度,并计算生物等效性。结果 艾司奥美拉唑在3~3 000 ng·mL^-1范围线性关系良好（r ≥ 0.999 4）,批内、批间精密度和准确度、回收率、基质效应及稳定性均符合生物样品测定要求。应用该方法进行人体生物等效性样品测定,证明受试制剂和参比制剂生物等效。结论 建立的人血浆中艾司奥美拉唑浓度测定方法准确、灵敏、选择性好、重现性高,可用于受试者单次口服40 mg艾司奥美拉唑镁肠溶干混悬剂的生物等效性研究,受试制剂和参比制剂生物等效。     

The development and validation of a method for quantifying olanzapine in human plasma by liquid chromatography tandem mass spectrometry and its application in a pharmacokinetic study

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Development and validation of an ultra‐fast and sensitive microflow liquid chromatography‐tandem mass spectrometry (MFLC‐MS/MS) method for quantification of LSD and its metabolites in plasma and application to a controlled LSD administration study in humans

Lysergic acid diethylamide (LSD) is a semi‐synthetic hallucinogen that has gained popularity as a recreational drug and has been investigated as an adjunct to psychotherapy. Analysis of LSD represents a major challenge in forensic toxicology due to its instability, low drug concentrations, and short detection windows in biological samples. A new, fast, and sensitive microflow liquid chromatography (MFLC) tandem mass spectrometry method for the validated quantification of LSD, iso‐LSD, 2‐oxo 3‐hydroxy‐LSD (oxo‐HO‐LSD), and N ‐desmethyl‐LSD (nor‐LSD) was developed in plasma and applied to a controlled pharmacokinetic (PK) study in humans to test whether LSD metabolites would offer for longer detection windows. Five hundred microlitres of plasma were extracted by solid phase extraction. Analysis was performed on a Sciex Eksigent MFLC system coupled to a Sciex 5500 QTrap. The method was validated according to (inter)‐national guidelines. MFLC allowed for separation of the mentioned analytes within 3 minutes and limits of quantification of 0.01 ng/mL. Validation criteria were fulfilled for all analytes. PK data could be calculated for LSD, iso‐LSD, and oxo‐HO‐LSD in all participants. Additionally, hydroxy‐LSD (HO‐LSD) and HO‐LSD glucuronide could be qualitatively detected and PK determined in 11 and 8 subjects, respectively. Nor‐LSD was only sporadically detected. Elimination half‐lives of iso‐LSD (median 12 h) and LSD metabolites (median 9, 7.4, 12, and 11 h for oxo‐HO‐LSD, HO‐LSD, HO‐LSD‐gluc, and nor‐LSD, respectively) exceeded those of LSD (median 4.2 h). However, screening for metabolites to increase detection windows in plasma seems not to be constructive due to their very low concentrations. Copyright © 2016 John Wiley & Sons, Ltd.     

UHPLC‐MS/MS and UHPLC‐HRMS identification of zolpidem and zopiclone main urinary metabolites and method development for their toxicological determination

Zolpidem and zopiclone (Z‐compounds) are non‐benzodiazepine hypnotics of new generation that can be used in drug‐facilitated sexual assault (DFSA). Their determination in biological fluids, mainly urine, is of primary importance; nevertheless, although they are excreted almost entirely as metabolites, available methods deal mainly with the determination of the unmetabolized drug. This paper describes a method for the determination in urine of Z‐compounds and their metabolites by ultra‐high‐pressure liquid chromatography/tandem mass spectrometry (UHPLC‐MS/MS) and UHPLC coupled with high resolution/high accuracy Orbitrap® mass spectrometry (UHPLC‐HRMS). The metabolic profile was studied on real samples collected from subjects in therapy with zolpidem or zopiclone; the main urinary metabolites were identified and their MS behaviour studied by MS/MS and HRMS. Two carboxy‐ and three hydroxy‐ metabolites, that could be also detected by gas chromatography/mass spectrometry (GC‐MS) as trimethylsylyl derivatives, have been identified for zolpidem. Also, at least one dihydroxilated metabolite was detected. As for zopiclone, the two main metabolites detected were N‐demethyl and N‐oxide zopiclone. For both substances, the unmetabolized compounds were excreted in low amounts in urine. In consideration of these data, a UHPLC‐MS/MS method for the determination of Z‐compounds and their main metabolites after isotopic dilution with deuterated analogues of zolpidem and zopiclone and direct injection of urine samples was set up. The proposed UHPLC‐MS/MS method appears to be practically applicable for the analysis of urine samples in analytical and forensic toxicology cases, as well as in cases of suspected DFSA. Copyright © 2013 John Wiley & Sons, Ltd.     

Development and validation of an LC–MS/MS method for quantification of NC-8 in rat plasma and its application to pharmacokinetic studies

ent-16-Oxobeyeran-19-N-methylureido (NC-8) is a recently synthesized derivative of iso-steviol that showed anti-hepatitis B virus (HBV) activity by disturbing replication and gene expression of the HBV and by inhibiting the host toll-like receptor 2/nuclear factor-κB signaling pathway. To study its pharmacokinetics as a part of the drug development process, a highly sensitive, rapid, and reliable liquid chromatography tandem mass spectrometry (LC–MS/MS) method was developed and validated for determining NC-8 in rat plasma. After protein precipitation extraction, the chromatographic separation of the analyte and internal standard (IS; diclofenac sodium) was performed on a reverse-phase Luna C₁₈ column coupled with a Quattro Ultima triple quadruple mass spectrometer in the multiple-reaction monitoring mode using the transitions, m/z 347.31 → 75.09 for NC-8 and m/z 295.89 → 214.06 for the IS. The lower limit of quantitation was 0.5 ng/mL. The linear scope of the standard curve was between 0.5 and 500 ng/mL. Both the precision (coefficient of variation; %) and accuracy (relative error; %) were within acceptable criteria of <15%. Recoveries ranged from 104% to 113.4%, and the matrix effects (absolute) were nonsignificant (CV ≤ 6%). The validated method was successfully applied to investigate the pharmacokinetics of NC-8 in male Sprague–Dawley rats. The present methodology provides an analytical means to better understand the preliminary pharmacokinetics of NC-8 for investigations on further drug development.     

液相色谱串联质谱法测定犬血浆中埃索美拉唑质量浓度及药动学研究

目的建立液相色谱联用质谱法(LC-MS/MS)测定犬血浆中埃索美拉唑(esomeprazole,EMZ)药物质量浓度,并用于其药动学进行研究。方法以地西泮为内标,血浆经乙腈沉淀蛋白处理,色谱柱为Shim-pack XR-ODS柱(100mm×2mm,5μm);流动相为乙腈:2mmol.L-1乙酸铵(含1mL.L-1甲酸);流速0.3mL.min-1;质谱条件:电喷雾离子化电离源ESI,正离子多反应检测,检测离子分别为346.2→198.2 m/z(埃索美拉唑)和285.2→193.2 m/z(地西泮)。采用DAS 2.0软件进行药动学参数估算。结果埃索美拉唑质量浓度在0.5～3 000μg.L-1范围内呈良好线性关系(r>0.99),最低定量限(LLOQ)为0.5μg.L-1,平均回收率为100.8%±6.7%,高、中、低3种质量浓度的日内和日间精密度实验RSD均小于15%。埃索美拉唑主要药动学参数AUC0-36,Cmax,tmax,t1/2z,CLz/F分别为(99 435.28±2 473.73)μg.h.L-1,(2 478.75±425.69)μg.L-1,(1.44±0.32)h,(3.41±2.86)h,(0.46±0.14)L.h-1.kg-1。结论该实验建立的分析方法专属性好,灵敏度高,准确快捷,适用于埃索美拉唑犬体内生物样品的分析。     

UPLC-MS/MS法测定大鼠血浆中间氯苯基哌嗪的质量浓度及其在药动学研究中的应用

目的建立测定大鼠血浆中间氯苯基哌嗪(m-chlorophenylpiperazine,m-CPP)的UPLC-MS/MS方法,并应用该法比较了按m-CPP计相同剂量下,大鼠灌胃给予盐酸WS和盐酸曲唑酮后,m-CPP在大鼠体内的药物动力学行为。方法色谱柱为Thermo Hypersi L GOLD a Q C18柱(100 mm×2.1mm,1.9μm),流动相为乙腈-体积分数0.1%甲酸水溶液梯度洗脱,采用乙腈沉淀蛋白法处理血浆样品,以正离子扫描多反应监测模式进行检测。结果大鼠血浆中的m-CPP在质量浓度为0.20~152.10μg·L-1内线性关系良好(r=0.998 4),定量下限为0.20μg·L-1,提取回收率大于85%,日内和日间精密度均小于7%,准确度为100.8%~103.5%。20只Sprague Dawley大鼠分别灌胃给予盐酸曲唑酮9.9 mg·kg-1(按m-CPP计4.8 mg·kg-1)和盐酸WS 10.2 mg·kg-1(按m-CPP计4.8mg·kg-1)生理盐水溶液,血浆中m-CPP的tmax分别为(0.6±0.3)和(0.6±0.2)h,ρmax分别为(32.6±16.2)和(22.3±12.0)μg·L-1,AUC0-10分别为(89.0±27.5)和(66.3±17.1)μg·h·L-1,AUC0-∞分别为(96.8±26.8)和(75.3±15.5)μg·h·L-1,t1/2分别为(3.1±1.6)和(4.0±3.9)h。结论盐酸WS组中m-CPP的AUC0-10和AUC0-∞均大于盐酸曲唑酮组(P<0.05),Cl小于盐酸曲唑酮组(P<0.05),其他药动学参数无显著性差异(P>0.05)。     

LC-MS/MS法同时测定人血浆中兰索拉唑与代谢产物的浓度及其药动学研究(英文)

目的建立同时测定人血浆中兰索拉唑及其代谢产物5’-羟基兰索拉唑和兰索拉唑砜的LC-MS/MS法。方法血浆样本用乙腈沉淀蛋白后,选用Zorbax SB-C18 Narrow-Bore色谱柱(150 mm×2.1 mm,5μm),以甲醇︰10 mmol.L-1乙酸铵(65︰35,V/V)为流动相,流速为0.4 mL.min-1。选用API3200型三重四极杆串联质谱仪的多重反应监测(MRM)扫描方式进行监测,电喷雾离子化源,负离子方式。结果兰索拉唑、5’-羟基兰索拉唑、兰索拉唑砜以及内标奥美拉唑的保留时间分别为2.63、1.56、2.21、2.30 min;血浆中兰索拉唑、5’-羟基兰索拉唑、兰索拉唑砜的线性范围分别为2.00～800、1.00～400、0.200～80.0μg.L-1(r>0.99),定量下限分别为2.00、1.00、0.200μg.L-1;日内、日间相对标准差(RSD)均小于8.0%;相对偏差(RE)均在±6.0%的范围以内;提取回收率较高,且可重现;兰索拉唑、5’-羟基兰索拉唑、兰索拉唑砜在各种贮存条件下均较稳定。该方法成功地应用于兰索拉唑肠溶片在中国健康人体内的药动学研究,兰索拉唑、5’-羟基兰索拉唑、兰索拉唑砜的ρmax分别为165～1400、15.8～177、10.2～530μg.L-1,AUC0-t分别为651～7 189、99.3～639、20.5～4 372μg.h.L-1。兰索拉唑及其代谢产物的药动学存在显著的个体间差异。结论该方法快速、灵敏、专属性强、重现性好,适用于兰索拉唑及其代谢产物的人体药动学研究。     

大鼠血浆中岩白菜素含量分析方法的建立及其体内药动学

目的建立血浆中岩白菜素的HPLC的测定方法,研究岩白菜素及岩白菜素磷脂复合物在大鼠体内的药动学行为。方法采用Odyssil C18色谱柱(250 mm×4.6 mm,5μm),流动相为甲醇-乙腈-质量分数为0.2%的磷酸水溶液(体积比为4∶16∶80),流速为0.8 m L·min-1,检测波长为220 nm。应用液-液萃取法处理血浆,测定两只大鼠分别口服岩白菜及其磷脂复合物后不同时刻血浆中岩白菜素的质量浓度。结果岩白菜素质量浓度在0.01~5 mg·L-1内线性关系良好,定量下限为0.01 mg·L-1;提取回收率均在78.6%~90%之间;日内、日间精密度均小于13.7%。结论该方法准确度高、灵敏度强、专属性好,可作为测定大鼠血浆岩白菜素质量浓度的方法,为探讨岩白菜素的药动学行为提供方法依据。     

Development and validation of an LC‐MS/MS method for simultaneous determination of piperaquine and 97‐63, the active metabolite of CDRI 97‐78, in rat plasma and its application in interaction study

Piperaquine‐dihydroartemisinin combination is the latest addition to the repertoire of ACTs recommended by the World Health Organization (WHO) for treatment of falciparum malaria. Due to the increasing resistance to artemisinin derivatives, CSIR‐CDRI has developed a prospective short acting, trioxane antimalarial derivative, CDRI 97‐78. In the present study, a liquid chromatography‐electrospray ionization‐tandem mass spectrometry (LC–ESI‐MS/MS) method for the simultaneous quantification of piperaquine (PPQ) and 97‐63, the active metabolite of CDRI 97‐78 found in vivo, was developed and validated in 100 μL rat plasma using halofantrine as internal standard. PPQ and 97‐63 were separated using acetonitrile:methanol (50:50, v/v) and ammonium formate buffer (10 mM, pH 4.5) in the ratio of 95:5(v/v) as mobile phase under isocratic conditions at a flow rate of 0.65 mL/min on Waters Atlantis C₁₈ (4.6 × 50 mm, 5.0 µm) column. The extraction recoveries of PPQ and 97‐63 ranged from 90.58 to 105.48%, while for the internal standard, it was 94.27%. The method was accurate and precise in the linearity range 3.9–250 ng/mL for both the analytes, with a correlation coefficient (r) of ≥ 0.998. The intra‐ and inter‐day assay precision ranged from 2.91 to 8.45% and; intra‐ and inter‐day assay accuracy was between 92.50 and 110.20% for both the analytes. The method was successfully applied to study the effect of oral co‐administration of PPQ on the pharmacokinetics of CDRI 97‐78 in Sprague‐dawley rats and vice versa. The co‐administration of CDRI 97‐78 caused significant decrease in AUC_0–∞ of PPQ from 31.52 ± 2.68 to 14.84 ± 4.33 h*µg/mL. However, co‐administration of PPQ did not have any significant effect on the pharmacokinetics of CDRI 97‐78. Copyright © 2015 John Wiley & Sons, Ltd.     

Development and validation of an LC‐MS/MS method after chiral derivatization for the simultaneous stereoselective determination of methylenedioxy‐methamphetamine (MDMA) and its phase I and II metabolites in human blood plasma

3,4‐Methylenedioxymethamphetamine (MDMA, ecstasy) is a racemic drug of abuse and its two enantiomers are known to differ in their dose‐response curves. The S‐enantiomer was shown to be eliminated at a higher rate than the R‐enantiomer. The most likely explanation for this is a stereoselective metabolism also claimed in in vitro studies. Urinary excretion studies showed that the main metabolites in humans are 4‐hydroxy 3‐methoxymethamphetamine (HMMA) 4‐sulfate, HMMA 4‐glucuronide and 3,4‐dihydroxymethamphetamine (DHMA) 3‐sulfate. For stereoselective pharmacokinetic analysis of phase I and phase II metabolites in human blood plasma useful analytical methods are needed. Therefore the aim of the presented study was the development and validation of a stereoselective liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method for the simultaneous quantification of MDMA, 3,4‐methylenedioxyamphetamine, DHMA, DHMA 3‐sulfate, HMMA, HMMA 4‐glucuronide, HMMA 4‐sulfate, and 4‐hydroxy 3‐methoxyamphetamine in blood plasma for evaluation of the stereoselective pharmacokinetics in humans. Blood plasma samples were prepared by simple protein precipitation and afterwards all analytes were derivatized using N‐(2,4‐dinitro‐5‐fluorophenyl) L‐valinamide resulting in the formation of diastereomers which were easily separable on standard reverse phase stationary phases. This simple and fast method was validated according to international guidelines including specificity, recovery, matrix effects, accuracy and precision, stabilities, and limits of quantification. The method proved to be selective, sensitive, accurate and precise for all tested analytes except for DHMA. Copyright © 2014 John Wiley & Sons, Ltd.     

An improved LC-MS/MS method for quantitative determination of ilaprazole and its metabolites in human plasma and its application to a pharmacokinetic study

Aim： To improve and validate an analytical method based on liquid chromatography and electrospray ionization tandem mass spectrometry （LC-ESI-MS/MS） for the quantitative measurement of ilaprazole and its two metablites in human plasma. Methods： Separation of analytes and the internal standard （IS）, omeprazole, was performed on a Thermo HyPURITY C18 column （150×2.1 mm, 5 um） with a mobile phase consisting of 10 mmol/L ammonium formate water-acetonitrile solution （50：50, v/v） at a flow rate of 0.25 mL/min. The API4000 triple quadruple mass spectrometer was operated in multiple reactions monitoring mode via positive electrospray ionization interface using the transition m/z 367.2 → m/z 184.0 for ilaprazole, m/z 383.3 → m/z 184.1 for ilaprazole sulfone, m/z 351.2 → m/z 168.1 for ilaprazole thiol ether and m/z 346.2 → m/z 198.0 for omeprazole. Results： The method was linear over the concentration range of 0.23-2400.00 ng/mL for ilaprazole, 0.05-105.00 ng/mL for ilaprazole thiol ether and 0.06-45.00 ng/mL for ilaprazole sulfone. The intra- and inter-day precisions were all less than 15% in terms of relative standard deviation （RSD）, and the accuracy was within 15% in terms of relative error （RE） for ilaprazole, ilaprazole sulfone and ilaprazole thiol ether. The lower limit of quantification （LLOQ） was identifiable and reproducible at 0.23, 0.05 and 0.06 ng/mL with acceptable precision and accuracy for ilaprazole, ilaprazole sulfone and ilaprazole thiol ether, respectively. Conclusion： The validated method offered sensitivity and a wide linear concentration range. This method was successfully applied for the evaluation of the pharmacokinetics of ilaprazole and its two metabolites after single oral doses of 5 mg ilaprazole to 12 healthy Chinese volunteers.     

超高效液相色谱串联质谱法测定大鼠血浆中埃索美拉唑质量浓度及药动学研究

目的：建立超高效液相色谱串联质谱（UPLC-ESI-MS/MS）法测定大鼠血浆中埃索美拉唑的含量,并应用于药动学研究。方法：血浆样品经蛋白沉淀法处理后,采用Agilent ZORBAX Eclipse Plus C₁₈色谱柱（50 mm×2.1 mm,1.8 μm）,以A（0.1%甲酸）-B（乙腈）（80：20）为流动相,柱温为35℃,采用电喷雾电离源（ESI）源,以多反应监测（MRM）方式进行正离子检测。通道分别为m/z 346→198（埃索美拉唑）和m/z 254→156（内标,磺胺甲卟唑）,用非室模型计算药动学参数。结果：埃索美拉唑的线性范围为0.2~20 ng·mL^-1（r=0.999 7）,检出限为0.12 ng·mL^-1,日内日间精密度均小于10%。低、中、高3个浓度提取回收率均大于90%,达峰时间（t_max）为（1.5±0.5）h,达峰浓度（C_max）为（620.65±2.89）ng·mL^-1,药物浓度-时间曲线下面积（AUC_0-t）为（2 530.68±60.17）ng·h·mL^-1,半衰期（t_1/2）为（3.87±0.03）h。结论：该方法操作简便、快速、准确度高、重复性好,可用于大鼠血浆中埃索美拉唑的测定和药动学研究。     

液-质联用法测定大鼠血浆中索他洛尔的浓度及其药动学研究

目的：建立大鼠血浆中索他洛尔的LC-MS/MS定量分析方法,考察口服给药后,索他洛尔在大鼠体内的药动学特征。方法：大鼠口服给药,分别在给药前和给药后不同的时间点从眼底静脉丛取血。采用LC-MS/MS分析方法,以阿替洛尔为内标测定大鼠血浆中索他洛尔的含量,并运用DAS1.0软件计算待测药物各药动学参数。结果：索他洛尔在5~5 000 ng·mL^-1范围内线性关系良好;日内日间精密度（RSD）范围为2.99%~5.75%,准确度（RE）为98.56~105.71%;提取回收率为92.50%~97.16%,基质效应为96.59%~102.10%。结论：所建立的LC-MS/MS分析方法准确、灵敏,可用于大鼠血浆中的索他洛尔的含量测定和药动学研究。     

LC-IT-MS/MS法测定大鼠体内商陆皂苷甲浓度及其药动学研究

目的:建立测定SD大鼠体内商陆皂苷甲(EsA)血药浓度的高效液相-离子阱串联质谱方法;研究EsA在SD大鼠体内的药动学特征。方法:采用Diamonsil C18色谱柱(50 mm×2.1 mm,3μm),流动相为甲醇-水(含0.1%冰醋酸)(70∶30),流速为0.2 mL.min-1,采用ESI源,正离子检测模式,以人参皂苷Rg1为内标,血浆样品经正丁醇液液萃取后进样分析,测定大鼠血浆中EsA浓度,BAPP软件计算主要药动学参数。结果:在选定的色谱条件下,EsA和内标分离良好,没有内源性物质干扰。EsA在5～500 ng.mL-1范围内线性良好(r=0.998 3),最低定量限为5 ng.mL-1,提取回收率大于70%,日内和日间精密度小于10%。SD大鼠灌胃给予EsA 15 mg.kg-1后,其主要药动学参数AUC0～24 h为(1 013.85±82.73)ng.h.mL-1,AUC0-∞为(1 076.31±92.70)ng.h.mL-1,t1/2为(6.16±0.63)h,Cmax为(218.80±38.33)ng.mL-1,Tmax为(0.8±0.1)h。结论:本方法简便快捷、灵敏准确;本研究所获得的EsA在SD大鼠体内的药动学参数为EsA的临床应用提供了依据。     

HPLC-MS/MS法测定人体血浆中丙泊酚的浓度及其药动学研究(英文)

目的:采用HPLC-MS/MS法检测人体血浆中丙泊酚的浓度,并将该方法用于临床药动学研究。方法:采用Zorb-ax Eclipse XDB-C18(50 mm×4.6 mm,5μm)色谱柱分离;流动相为甲醇和0.1%氨水二元梯度洗脱系统;流速为0.3 mL.min-1;通过电喷雾离子化电离源(ESI),采用负离子检测。结果:线性范围为0.010～12μg.mL-1,相关系数≥0.99,定量下限为0.010μg.mL-1。日内及日间精密度不高于15%,准确度的相对误差(RE)在-2.0%～5.0%。药代动力学符合三室模型,清除率为0.029 L.min-1.kg-1,中央室分布容积为0.60 L.kg-1,血药浓度消除半衰期t1/2α为0.84 min,t1/2β为6.7 min,t1/2γ为128.7 min。结论:该方法高效、灵敏,特异性强,准确度、精密度好,适用于丙泊酚药物动力学研究。     

Development and validation of a semi-automated method for L-dopa and dopamine in rat plasma using electrospray LC/MS/MS

A semi-automated alumina-based extraction method for the determination of L-dopa and dopamine in plasma using liquid chromatography mass spectrometry was validated. The method exploited the use of a Tomtec Quadra 96 liquid handing robot to expedite aluminum oxide extraction for sample clean up. Two 96-well sample plates can be processed in less than 2 h and extracts, collected in a 96-well plate format, can be directly injected onto the ESI/LC/MS/MS instrumentation. Chromatographic separation of the analytes was performed on a reverse-phase ODS column (TosoHaas ODS-80) with a mobile phase of acetonitrile/0.1% formic acid (5/95 v/v) at a flow rate of 0.22 ml/min. Analytes were detected by a triple-quadruple mass spectrometer equipped with an electrospray ionization source (ESI). Recoveries were evaluated for a number of pH modifiers and elution solvents. Under optimized conditions, the mean recoveries of L-dopa and dopamine were 56 and 67%, respectively. Intra-run and inter-run precision, calculated as percent relative standard deviation of replicate quality controls, was in the range of 1.45-10.8% for both L-dopa and dopamine. Intra-run and inter-run accuracy, calculated as percent error, was in the range -2.5 to 6.69% for both analytes. The limit of quantitaiton was 2.5 ng/ml for both L-dopa and dopamine when 100 microl of plasma was extracted. The method is simple, rapid, accurate and suitable for the quantification of L-dopa and dopamine in plasma or other biological fluid samples from clinical, preclinical, or pharmacological studies.