液相色谱-串联质谱法测定人血浆中奥美拉唑的血药浓度及其药动学

目的:建立液相色谱-串联质谱法测定人血浆中奥美拉唑的血药浓度并进行药动学研究。方法:以兰索拉唑为内标,血浆样品经乙腈沉淀后,经LC-MS/MS分离分析。采用Diamonsil C₁₈柱(2.1 mm×150 mm,5 μm),甲醇-水(含0.01%甲酸)(67:33)为流动相;流速为0.3 ml·min^-1,采用电喷雾离子源(ESI),以多反应监测方式(MRM)进行负离子监测,奥美拉唑和兰索拉唑的定量分析离子对分别为m/z 344.2/193.8,367.9/163.8。结果:奥美拉唑在3.38~2 110.00 ng·ml^-1 (r=0.997 1)范围内线性关系良好,最低定量限为3.38 ng·ml^-1,方法回收率在92.48%~99.39%,日内(n=5)RE均小于3.96%,日间(n=15)RE均小于6.41%。结论:该方法快速简便,灵敏准确,可用于奥美拉唑血药浓度监测和药动学研究。     

LC/MS/MS法测定血浆、羊水中曲马多及其活性代谢物氧去甲基曲马多LC/MS/MS法测定血浆、羊水中曲马多及其活性代谢物氧去甲基曲马多

目的建立液相色谱-串联质谱法(LC/MS/MS)同时测定血浆和羊水中曲马多和氧去甲基曲马多，并研究其在母体和胎儿体内分布。方法生物样本经液-液提取，通过液相色谱-串联质谱，以选择离子反应监测(SRM)方式进行检测。结果测定血浆样品曲马多和氧去甲基曲马多的线性范围为8.0~800.0 μg·L^-1；测定羊水样品曲马多和氧去甲基曲马多的线性范围为1.0~400.0 μg·L^-1。12例剖宫产产妇术前im盐酸曲马多(1.5 mg·kg^-1)后，血浆中曲马多和氧去甲基曲马多浓度较高，羊水中曲马多浓度较低，且未检测出氧去甲基曲马多。结论本方法操作简便、灵敏度高，可用于临床药代动力学研究。     

Significant enhancement of 11‐Hydroxy‐THC detection by formation of picolinic acid esters and application of liquid chromatography/multi stage mass spectrometry (LC‐MS3): Application to hair and oral fluid analysis

Formation of picolinic acid esters of hydroxylated drugs or their biotransformation products is a promising tool to improve their mass spectrometric ionization efficiency, alter their fragmentation behaviour and enhance sensitivity and specificity of their detection. The procedure was optimized and tested for the detection of cannabinoids, which proved to be most challenging when dealing with alternative specimens, for example hair and oral fluid. In particular, the detection of the THC metabolites hydroxyl‐THC and carboxy‐THC requires ultimate sensitivity because of their poor incorporation into hair or saliva. Both biotransformation products are widely accepted as incorporation markers to distinguish drug consumption from passive contamination. The derivatization procedure was carried out by adding a mixture of picolinic acid, 4‐(dimethylamino)pyridine and 2‐methyl‐6‐nitrobenzoic anhydride in tetrahydrofuran/triethylamine to the dry extraction residues. Resulting derivatives were found to be very stable and could be reconstituted in aqueous or organic buffers and subsequently analyzed by liquid chromatography‐mass spectrometry (LC‐MS). Owing to the complex consecutive fragmentation patterns, the application of multistage MS3 proved to be extremely useful for a sensitive identification of doubly picolinated hydroxy‐THC in complex matrices. The detection limits – estimated by comparison of corresponding signal‐to‐noise ratios – increased by a factor of 100 following picolination. All other species examined, like cannabinol, THC, cannabidiol, and carboxy‐THC, could also be derivatized exhibiting only moderate sensitivity improvements. The assay was systematically tested using hair samples and exemplarily applied to oral fluid. Concentrations of OH‐THC identified in THC‐positive hair samples ranged from 0.02 to 0.29pg/mg. Copyright © 2014 John Wiley & Sons, Ltd.     

LC-MS/MS法测定人血浆中的辅酶Q10

目的:建立一种快速、灵敏的LC-MS/MS法测定人血浆中的辅酶Q10。方法:血浆样品经正己烷液-液萃取2次,以甲醇为流动相,CapcellPakC18柱(35mm×2.0mm,5μm)进行分离,采用大气压化学电离源,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反应分别为m/z864→197(辅酶Q10)和m/z796→197(内标辅酶Q9)。结果:测定血浆中辅酶Q10的线性范围为10.0～1000ng·mL-1,定量下限可达10.0ng·mL-1,日内、日间精密度(RSD)均小于8.9%,准确度(RE)在-0.9%～3.8%之间,单个样品分析时间为4.5min。结论:本方法分析测试时间短,灵敏度较高,血浆用量少,适用于人血浆样品中辅酶Q10的测定和药物动力学研究。     

液相色谱-串联质谱法测定人血浆中卡维地洛的浓度

目的建立测定血浆中卡维地洛的液相色谱-串联质谱(LC-MS/MS)方法。方法血浆样品中加入内标氘3-卡维地洛,直接沉淀法处理样品。色谱柱为CAPCELL PACK C_(18)Ⅲ(100.0mm×2.0mm,5μm),流动相为含0.1%甲酸的水溶液-含0.1%甲酸的乙腈溶液(70:30,V/V),流速0.5mL·min~(-1),等度洗脱,进样体积8μL,正离子多离子反应监测(MRM)扫描分析,离子通道分别为m/z 407.3→100.1(卡维地洛),m/z 410.3→100.1(氘3-卡维地洛)。结果卡维地洛线性范围为0.2～200μg·L~(-1)(r>0.999),定量下限为0.2μg·L~(-1),提取回收率在92.27%～104.0%,日内、日间精密度RSD均小于8%。结论本方法操作简便,特异性强,灵敏度高,可适用于卡维地洛的药动学研究。     

液相色谱-串联质谱法同时测定人血浆中厄贝沙坦和氢氯噻嗪的浓度及药动学

目的建立液相色谱-串联质谱法同时测定血浆中厄贝沙坦和氢氯噻嗪的浓度,并用于人体药动学研究。方法 20名健康受试者单剂量口服试验制剂1片(厄贝沙坦150 mg,氢氯噻嗪12.5 mg)后,在0～36 h内不同时间点分别采集血样,分取血浆,以氯沙坦为内标,经甲醇沉淀蛋白浓缩后流动相溶解,采用CuroSil-PFP色谱柱(Phenomenex 250 mm×4.6 mm,5μm),用含4%冰醋酸的水和含4%冰醋酸的甲醇-乙腈(1∶1,V/V)的流动相梯度洗脱分离,电喷雾离子化串联质谱选择性反应监测(SRM),分别采用正和负离子切换测定厄贝沙坦和氢氯噻嗪在血浆中的浓度。结果厄贝沙坦和氢氯噻嗪血浆样品分别在10～4 000μg.L-1和1～400μg.L-1的浓度范围内质谱响应线性良好。定量下限(LLOQ)分别为10.0μg.L-1和1.0μg.L-1,准确度和精密度良好。受试者单剂量口服厄贝沙坦氢氯噻嗪片1片后,测得氢氯噻嗪的ρmax、tmax、AUC0-36和t1/2分别为(86.96±34.99)μg.L-1、(1.75±0.69)h、(434±143)μg.h.L-1和(7.91±1.31)h;厄贝沙坦的相应参数分别为(1 670±409)μg.L-1、(1.55±0.70)h、(7 396±274)μg.h.L-1和(9.45±5.20)h。结论本方法专属性强、灵敏度高、准确性高,满足厄贝沙坦和氢氯噻嗪药动学研究的要求。     

UPLC-MS/MS法测定小鼠血浆及脑组织中马钱子碱浓度

目的建立小鼠血浆及脑组织中马钱子碱浓度的UPLC-MS/MS测定方法 ,用于小鼠马钱子碱药动学研究。方法色谱柱为Acquity UPLC BEHC18柱（2.1mm×50mm,1.7μm）。流动相为水（含0.1%甲酸）-甲醇（75：25,v/v）,流速0.25mL.min-1,柱温40℃。吗氯贝胺为内标,采用ESI＋模式,多重反应选择离子检测,马钱子碱m/z395→324,吗氯贝胺m/z269→182。样品处理采用液液萃取。结果马钱子碱在小鼠血浆中线性范围为5.016～5016ng.mL-1,脑组织中线性范围为3.009～725.4ng.g-1,日内精密度（RSD）均〈8.5%,日间精密度（RSD）均〈11.2%,方法回收率范围血浆中为91.7%～112.9%,脑组织中为95.6%～107.2%。结论本方法简单、灵敏、准确,适用于小鼠体内马钱子碱浓度测定及药动力学研究。     

液相色谱-串联质谱法测定人血浆中瑞舒伐他汀钙浓度及临床药代动力学研究

目的：建立测定人血浆中瑞舒伐他汀钙的液相色谱．串联质谱法，考察瑞舒伐他汀钙在中国健康志愿者体内的药代动力学。方法：含有瑞舒伐他汀钙和氟伐他汀钠的血浆样品经液-液提取后，进行色谱分析，在三重四极杆串联质谱仪上，以多反应离子监测方式进行定量分析。结果：瑞舒伐他汀钙的定量下限为0．03ng／mL，线形范围为0．03～60ng／mL，精密度与准确度符合生物样品分析要求。结论：该方法操作简便、快速、灵敏度高，适合瑞舒伐他汀钙的临床药代动力学研究。     

Long‐term stability of cannabinoids in oral fluid after controlled cannabis administration

Cannabinoid stability in oral fluid (OF) is important for assuring accurate results since OF has become a valid alternative matrix of choice for drug testing. We previously published OF cannabinoid stability studies using Quantisal™, Oral‐Eze®, and StatSure™ devices stored at room temperature for 1 week, 4 °C for up to 4 weeks, and at ‐20 °C up to 24 weeks. Extending refrigerated stability up to 3 months would be helpful for clinical and forensic testing, for re‐analysis of OF samples and for batching research analyses. Individual authentic OF pools were prepared after controlled smoking of a 6.9% ∆⁹‐tetrahydracannabinol cannabis cigarette; the Quantisal™ device was utilized for OF collection. Fifteen healthy volunteers participated in the Institutional Review Board‐approved study. Stability for THC, 11‐nor‐9‐carboxy‐THC (THCCOOH), ∆⁹‐tetrahydrocannabivarin (THCV), cannabidiol (CBD), and cannabigerol (CBG) were determined after storage at 4 °C for 1, 2, and 3 months. Results within ±20% of baseline concentrations were considered stable. All analytes were stable for up to 2 months at 4 °C for all participants with positive baseline concentrations. Baseline concentrations were highly variable. In total, THC, THCCOOH, THCV, CBD, and CBG were stable for 3 months at 4 °C for pooled positive specimens from 14 of 15, 8 of 9, 7 of 8, 8 of 9, and 9 of 10 participants, respectively. In conclusion, Quantisal™‐collected OF specimens should be stored at 4 °C for no more than two months to assure accurate THC, THCCOOH, THCV, CBD, and CBG quantitative results; only one participant's OF was unstable at three months. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.     

液相色谱-串联质谱法测定犬血管组织中雷帕霉素的含量

目的建立犬血管组织中雷帕霉素含量测定的液相色谱-串联质谱方法。方法采用AgilentZorbax C18(2.1 mm×100 mm,3.5μm)色谱柱,流动相为甲醇-水(含10 mmol.L-1醋酸铵,0.08%甲酸)(85∶15,V/V),流速为0.2 mL.min-1;电喷雾离子源,负离子电离模式,选择性反应监测扫描方式,雷帕霉素和罗红霉素(内标)检测的离子对分别为m/z 936.0→m/z 409.0和m/z 837.0→m/z 679.2。结果雷帕霉素在1～1 500μg.L-1浓度范围内有良好的线性关系(r=0.997 6),最低检测限为0.3μg.L-1,日内、日间精密度(RSD)均小于6.7%,提取回收率在81.8%～86.3%范围内,相对回收率在104.4%～109.8%范围内。结论本法简便、快速、灵敏、准确,可用于测定血管组织中雷帕霉素的含量。     

Simultaneous quantification of 19 nonsteroidal anti-inflammatory drugs in oral fluid by liquid chromatography-high resolution mass spectrometry: Application on ultratrail runner's oral fluid

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a therapeutic class suspected to be used by ultratrail runners. The use of NSAIDs during ultratrails is known to be associated with various adverse effects. To study the prevalence of NSAIDs intake in ultratrail runners, oral fluid (OF) is a relevant matrix as it is noninvasive and easy to collect. The aim of our work was to develop and validate a liquid–liquid extraction followed by a liquid chromatography (LC)–mass spectrometry (MS)/high resolution mass spectrometry (HRMS) method for the simultaneous quantification of 19 NSAIDs in OF. After a comparison of different liquid–liquid extraction methods, a double step liquid–liquid extraction with chloroform was performed on OF collected with Quantisal®, with extraction recoveries higher than 90%. An Accucore AQ column was selected for the chromatographic separation of NSAIDs. The Q Exactive Plus mass spectrometer operated in full scan and ddms2 mode after positive and negative electrospray ionization. Selectivity, carry-over, matrix effect, and linearity were validated for all NSAIDs. Within-day and between-day accuracy and precision were validated for all NSAIDs (<15% for quality control [QC] samples and <20% for lower limit of quantitation [LLOQ]), except within-day accuracy for the LLOQ of mefenamic acid. A stability study was also performed on OF at room temperature and +4°C. The method was applied on OF from runners who participate to Ultra Trail du Mont Blanc®.     

液相色谱串联质谱法测定人血浆中文拉法辛及其代谢物的浓度

目的建立测定血浆中文拉法辛及其代谢物O-去甲基文拉法辛的液相色谱串联质谱(LC-MS/MS)方法。方法血浆样品中加入内标(氘6-文拉法辛和氘6-O-去甲基文拉法辛),直接沉淀法处理样品。色谱柱为CAPCELL PAK C18 MGⅢ分析柱(100 mm×2.0 mm,5μm),流动相为含0.3%甲酸的水溶液-含0.3%甲酸的乙腈溶液(78∶22,V/V),流速为0.3 mL.min-1。正离子多离子反应监测(MRM)扫描分析,离子通道分别为m/z 278→58(文拉法辛)、m/z 264→58(O-去甲基文拉法辛)、m/z 284→58(氘6-文拉法辛)、m/z 270→58(氘6-O-去甲基文拉法辛)。结果文拉法辛和O-去甲基文拉法辛的线性范围均为2～1 000μg.L-1,定量下限均为2μg.L-1,提取回收率在90.14%～97.33%,批内、批间RSD均小于8%。结论本方法操作简便,特异性强,灵敏度高,可用于人血浆内文拉法辛和O-去甲基文拉法辛的含量测定研究。     

LC-MS/MS法测定大鼠血浆中亚胺培南浓度及其药动学研究

目的：建立了一种测定大鼠血浆中亚胺培南（IMP）浓度的LC-MS/MS方法,研究不同剂量的IMP在SD大鼠中的药代动力学特征。方法：大鼠血浆样品使用乙腈蛋白沉淀,色谱柱采用Phenomenex Kinetex@ HILIC柱（50 mm × 2.1 mm,2.6 μm）,流动相为0.1%甲酸水溶液（含5 mmol·L-1乙酸铵）-乙腈,行梯度洗脱。采用电喷雾离子源（ESI）,正离子多反应监测模式（MRM）,IMP定量离子对为m/z 300.0 → m/z 142.0。大鼠腹腔注射IMP（50、100和200 mg·kg-1）后于不同时间采血并检测其血药浓度,计算药代动力学参数。结果：测定血浆中IMP的线性范围为0.20 ~ 200 μg·mL-1,日内及日间精密度（RSD）均< 11.46%,准确度为91.67% ~ 105.38%,基质效应为91.33% ~ 104.63%,回收率为88.90% ~ 101.55%,均符合生物样品的分析要求。大鼠腹腔注射50、100和200 mg·kg-1 IMP后主要药动学参数Cmax分别为（86.15 ± 31.59）、（165.59 ± 23.57）和（322.32 ± 63.97）μg·mL-1;t1/2分别为（26.31 ± 6.87）、（29.90 ± 2.27）和（49.71 ± 5.25）min;AUC0-∞分别为（5 261.40 ± 1 513.08）、（13 803.56 ± 1 308.5）和（36 412.38 ± 6 309.41）μg·min-1·mL-1。结论：本法准确、灵敏,适用于大鼠腹腔注射不同剂量IMP后的浓度检测及药代动力学研究。     

液相色谱-串联质谱法测定健康人体血浆中米格列醇浓度及其药代动力学研究

目的建立测定血浆中米格列醇片(降血糖药)的液相色谱-串联质谱法,考察米格列醇在中国健康志愿者体内的药代动力学。方法血浆样品经液-液提取后,进行色谱分离,在三重四极杆串联质谱仪上,以多反应离子监测(MRM)方式进行定量分析,用于监测的离子为m/z 208．3→m／z 146．1 (米格列醇)和m/z 268．5→m/z 250．4(内标,伏格列波糖)。结果米格列醇的最低定量浓度为5．0 μg·L-1,线性范围为5～2 000 μg·L-1,精密度与准确度符合生物样品分析要求。结论该法操作简便、快速、灵敏度高,适于临床药代动力学研究。     

LC-MS/MS法测定比格犬血浆中红景天苷和酪醇的浓度及其药动学研究

目的:建立LC-MS/MS法测定比格犬血浆中红景天苷及其代谢物酪醇的浓度,并应用于药动学研究.方法:血浆样品经氯仿、苯酚和异戊醇混合溶剂萃取,Shimadzu Shim-pack Velox PFPP色谱柱(100 mm×2.1 mm,1.8 μm)分离,以水(A相)-含20％乙腈的甲醇溶液(B相)为流动相,梯度洗脱(...     

液相色谱-串联质谱法测定健康人体内阿德福韦浓度及其药动学研究(英文)

目的建立人血浆和尿样中阿德福韦浓度的液相色谱-串联质谱(LC-MS/MS)测定方法。方法10名健康受试者单剂量口服阿德福韦10mg。于服药前(0h)和服药后抽取静脉血及留取尿样。采用BDS-Phenyl column(250mm×4.6mm,5μm)色谱柱,流动相为甲醇-0.35mol·L-1冰醋酸梯度洗脱,流速为0.3mL.min-1;电喷雾离子化正离子选择性反应检测;检测离子为m/z274.1→162.1(阿德福韦),m/z254.1→135.0(喷昔洛韦,内标)。结果LC-MS/MS测定阿德福韦血浆样品线性范围为0.50～200μg.L-1,尿样线性范围为50～20000μg·L-1,线性关系良好。血浆样品分析的回收率、精密度和准确度均良好,定量限为0.50μg·L-1。主要药动学参数为:ρmax(24±s4)μg·L-1,tmax(1.0±0.6)h,AUC0～t(278±45)h.μg·L-1,AUC0～∞(285±45)h.μg·L-1,t1/2(8.8±1.6)h,CL(F)(36±6)L.h-1,Vd(F)(456±136)L,0～48h的尿累计排泄量为(48±12)%。结论建立的LC-MS/MS测定法专属性强、灵敏度适宜,可以用于阿德福韦的药动学研究。     

用液相色谱-串联质谱法测定人血浆中血小板活化因子

目的：建立一种人血浆中血小板活化因子（PAF）的液相色谱－串联质谱测定方法（LC-MS／MS），从而反映临床冠心病独立风险预测因子脂蛋白相关磷脂酶A2（LP－PLA2）活性。方法：血浆添加底物PAF后，37℃孵育10min，加入甲醇沉淀蛋白质，离心取上清进样。血浆PAF经HPLC法分离，串联质谱法定量检测。以PAF的单位时间减少量来衡量LP—PLAa的活性。结果：在1～50μg／mL添加浓度范围内线性关系良好，线性方程y=0．284c＋0．214，r=0．9991（n=6）。低、中、高浓度（3、20、40μg／mL）质控品的批内、批间精密度分别为2．08％～4．75％（n=6）和5．47％～5．86％（n=18），准确度为93．50％～97．66％，PAF和内标非布索坦的回收率为97．36％～100．8％（n=6）。稳定性研究结果表明，PAF在样品预处理后12h和冻融3次后的准确度为99．96此～107．1％（，产6），说明稳定性良好。应用本方法测定10例冠心病患者和健康对照组的PAF反应量，测定结果分别为（22．77±1．26）mg／mL和（19．62±3．94）mg／mL，说明冠心病患者LP—PLA2活性明显高于健康对照组（P＜0．05）。结论：本方法专一灵敏、准确可靠、重复性好、检测通量高，可作为心血管疾病诊断指标之一，用于临床冠心病与缺血性卒中风险预测的研究。     

LC-MS/MS法分析人血浆中西格列汀浓度及其应用研究

摘要：目的 建立一种测定人血浆中西格列汀浓度的液相色谱-串联质谱（LC-MS/MS）分析方法,并将该方法应 用于西格列汀在人体内的药代动力学研究。方法 以西格列汀-d4为内标,血浆样品经CleanertPPT沉淀板沉淀后, 通过Diamonsil C18色谱柱（100 mm×4.6 mm,5 μm）进行分离,使用甲醇-10 mmol/L甲酸铵水溶液（含10%甲醇,0.1% 甲酸）作为流动相,进行梯度洗脱,流速为0.5 mL/min。通过电喷雾电离源（ESI）,以多反应监测（MRM）模式进行正离 子检测。从选择性、残留、线性范围与定量下限、精密度与准确度、基质效应和回收率、稳定性方面进行方法学验证。 同时考察健康人口服西格列汀片100 mg后的主要药代动力学参数。结果 西格列汀、西格列汀-d4的MRM离子对 分别为 m/z 408.0→235.2、m/z 412.1→239.0。人血浆中西格列汀在 0.5～1 000 μg/L 浓度范围内线性关系良好（R2> 0.99）,定量下限为0.5 μg/L;定量下限和质控样品的批内、批间精密度（RSD）在0.83%~12.80%之间,准确度（RE）在± 10.0%以内。健康人口服西格列汀片100 mg后主要药代动力学参数：达峰时间（Tmax）、达峰浓度（Cmax）、、生物利用度 （AUC）、半衰期（T1/2）分别为（2.44±1.29）h、（375±138）μg/L、（2 915±585）h·μg/L、（11.10±2.41）h。结论 本LC-MS/ MS分析方法敏感度高且样品处理方法简单快速,满足生物分析的法规要求,可应用于人体内西格列汀的药代动力学 研究。     

液相色谱-串联质谱法快速测定兔血清及组织中痕量氟尿嘧啶

目的建立灵敏、快速的液相色谱-串联质谱法测定兔血清及组织中氟尿嘧啶的浓度。方法血清及组织样本经乙酸乙酯一步提取后,以乙腈-水(70:30,V/V)为流动相,Hypercarb C_(18)柱分离,采用电喷雾电离源,以多反应离子检测(MRM)方式进行负离子检测。用于定量分析的离子反应分别为m/z128.9→m/z41.9(氟尿嘧啶)和m/z188.7→m/z41.9(内标,溴尿嘧啶)。结果测定血清中氟尿嘧啶的线性范围为0.25～50μg·L~(-1),定量下限为0.25μg·L~(-1)。日内、日间精密度(RSD)均小于11%。食管组织中氟尿嘧啶的线性范围为0.5～100μg·L~(-1),定量下限为0.50μg·L~(-1)。日内、日间精密度(RSD)均小于10%。结论该法选择性强、灵敏度很高、操作简便、分析时间短,且可同时测定血清及组织中药物浓度,适用于极低浓度氟尿嘧啶生物样本的大批量检测。     

液相色谱-串联质谱法测定人血浆中替扎尼定

目的:建立灵敏的液相色谱-串联质谱法测定人血浆中替扎尼定的浓度。方法:血浆样品碱化后经乙醚液-液萃取,以甲醇-10 mmo·lL-1醋酸铵-甲酸(55∶45∶0.1,v/v/v)为流动相,采用Zorbax SB C18柱(150 mm×4.6 mm,5μm)分离,通过电喷雾电离源,以选择反应监测(SRM)方式进行正离子检测,用于定量分析的离子反应分别为m/z254→44(替扎尼定)和m/z243→210(内标,石杉碱甲)。结果:测定血浆中替扎尼定方法的线性范围为10.0～5000 pg·mL-1,定量下限可达10.0 pg·mL-1。日内、日间精密度(RSD)均小于10.0%,准确度(RE)在±3.6%以内。结论:本方法灵敏度高,血浆用量少,适用于替扎尼定制剂的人体药物动力学研究。