Identification and quantification of metabolites of arachidonic acid from cultures of endothelial cells by HPLC-MS2

Epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids (HETEs) are oxidative products of arachidonic acid, some of which participate in the regulation of vascular tone. Little is known about the production of EETs and HETEs in cultures of endothelial cells. This paper reports an assay for the simultaneous quantification of isomers of EETs and HETEs from endothelial cell culture supernatants by employing solid-phase extraction and liquid chromatography-mass spectrometry. The method enabled measurement of 5,6-EET, 8,9-EET, 11,12-EET, 14,15-EET, 5-HETE, 8-HETE, 11-HETE, 12-HETE and 15-HETE. The metabolites were chromatographically separated by reversed-phase HPLC and identified by negative ESI tandem mass spectrometry and this method was used to investigate the metabolism of arachidonic acid with an endothelial cell line. For quantification, the sum of signal intensities of characteristic fragment ions was used. The detection limits for 5,6-EET and of other EET and HETE isomers were 2.0, 0.64 and 8 ng ml(-1) culture medium, respectively. The precision of the method was determined with spiked culture medium (three concentrations, n = 5) and the average RSD ranged from 6.0 to 24.2%. The dynamic range was 0.6-23.5 ng ml(-1) culture medium for EETs and 8.0-200 ng ml(-1) for HETEs. Arachidonic acid was mainly metabolised to HETEs with product levels ranging from 59.3 to 460 ng 10(-6) cells. The median of 8,9-EET and 14,15-EET was 14.5 and 17.7 ng 10(-6) cells, respectively, whereas 5,6-EET and 11,12-EET were below 2 ng 10(-6) cells in a 5-min incubation assay at a 30 microM arachidonic acid substrate concentration.     

A liquid chromatography/mass spectrometric method for simultaneous analysis of arachidonic acid and its endogenous eicosanoid metabolites prostaglandins, dihydroxyeicosatrienoic acids, hydroxyeicosatetraenoic acids, and epoxyeicosatrienoic acids in rat brain tissue

A sensitive, specific, and robust liquid chromatography/mass spectrometric (LC/MS) method was developed and validated that allows simultaneous analysis of arachidonic acid (AA) and its cyclooxygenase, cytochrome P450, and lipoxygenase pathway metabolites prostaglandins (PGs), dihydroxyeicosatrienoic acids (DiHETrEs), hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs), including PGF(2alpha), PGE(2), PGD(2), PGJ(2), 14,15-DiHETrE, 11,12-DiHETrE, 8,9-DiHETrE, 5,6-DiHETrE, 20-HETE, 15-HETE, 12-HETE, 9-HETE, 8-HETE, 5-HETE, 14,15-EET, 11,12-EET, 8,9-EET, and 5,6-EET in rat brain tissues. Deuterium labeled PGF(2alpha)-d(4), PGD(2)-d(4), 15(S)-HETE-d(8), 14,15-EET-d(8), 11,12-EET-d(8), 8,9-EET-d(8), and AA-d(8) were used as internal standards. Solid phase extraction was used for sample preparation. A gradient LC/MS method using a C18 column and electrospray ionization source under negative ion mode was optimized for the best sensitivity and separation within 35 min. The method validation, including LC/MS instrument qualification, specificity, calibration model, accuracy, precision (without brain matrix and with brain matrix), and extraction efficiency were performed. The linear ranges of the calibration curves were 2-1000 pg for PGs, DiHETrEs, HETEs, and EETs, 10-2400 pg for PGE(2) and PGD(2), and 20-2000 ng for AA, respectively.     

高效液相色谱-串联质谱法测定人血浆中替加色罗的浓度

目的:建立人血浆中替加色罗浓度的高效液相色谱-串联质谱测定方法。方法:血浆样本经固相萃取(solid-phase extraction,SPE)小柱提取处理后进行色谱分离,质谱条件为电喷雾电离源,采用多反应监测(multiplereaction monitoring,MRM)方式进行定量分析,用于监测的离子为m/z302.1→172.8(替加色罗)和m/z466→183.8(内标,西沙必利)。结果:血浆中替加色罗检测方法的线性范围为0.1~50 ng.mL-1,最低定量限为0.1 ng.mL-1。血浆中替加色罗的绝对回收率为99.4%~104.2%,日内及日间精密度分别低于5%和6%,符合生物样品分析要求。结论:本法灵敏,准确,可用于替加色罗的药动学及生物等效性的研究。     

用HPLC-MS/MS法同时测定Caco-2细胞单层转运介质中吗替麦考酚酯和麦考酚酸的浓度

目的:建立HPLC-MS/MS法同时测定Caco-2细胞单层转运介质中吗替麦考酚酯(mycophenolate mofetil,MMF)和麦考酚酸(mycophenolic acid,MPA)的浓度,用于药物转运实验研究。方法:采用Zorbax Eclipse XDB-C18色谱柱(50mm×2.1mm,3.5μm);流动相A相:甲醇(含0.05%甲酸),B相:水(含0.05%甲酸);梯度洗脱:0～3.60min,40%A,流速:0.3ml/min,3.61～7.00min,65%A,流速:0.6ml/min,7.01～10.00min,40%A,流速:0.6ml/min;柱温:30℃,以吲哚美辛为内标。质谱检测方式:多种反应监测(MRM),选择监测的离子为:m/z433.8→194.8(MMF),m/z319.1→191.0(MPA)和m/z356.0→312.1(吲哚美辛)。结果:MMF和MPA检测的线性范围均为0.01～20μmol/L,线性回归方程分别为MMF:As/Ai=-0.035 2+0.394 5 c(r=0.999 1);MPA:As/Ai=0.005 5+0.050 8 c(r=0.999 5)。低、中、高浓度(0.1、1.5、15μmol/L)MMF的回收率分别为(103.2±7.5)%、(97.3±3.1)%和(96.0±3.4)%,日内、日间RSD<7.27%;低、中、高浓度(0.1、1.5、15μmol/L)MPA的回收率分别为(106.9±1.0)%、(106.0±5.7)%和(108.4±3.2)%,日内、日间RSD<9.25%(n=5)。结论:本研究建立的测定方法简便、准确、灵敏度高,适用于MMF和MPA体外转运实验研究。     

HPLC-MS/MS法同时测定人血浆中替格瑞洛和阿司匹林及其代谢物

目的:建立液相色谱-质谱(HPLC-MS/MS)法同时测定人血浆中替格瑞洛、AR-C124910XX、阿司匹林和水杨酸的浓度.方法:色谱柱:Diamonsil C18(150.0mm×4.6mm,3.5μm),流动相:乙腈(B)-0.2％甲酸水溶液(A),梯度洗脱;流速:0.8 mL·min-1;柱温:35℃;进样量:...     

高效液相色谱-串联质谱测定人血浆中依普利酮的浓度及其药动学

目的研究依普利酮片单次及多次给药后的人体药动学。方法 30名健康志愿者分为三组,分别服用依普利酮片50、100、200 mg,其中100 mg组为多次给药组,连续给药7 d;采集24 h内动态血标本,高效液相色谱-串联质谱法测定血浆中依普利酮的浓度,并采用DAS 3.2.4软件对试验数据进行处理,计算药动学参数。结果单次口服50、100和200 mg依普利酮片的主要药动学参数ρ_(max)分别为(723.20±203.59)、(1 212.47±249.52)、(2 053.32±394.06)μg·L^(-1),t_(max)分别为(1.8±0.7)、(2.1±0.9)、(1.9±0.4)h,t_(1/2)分别为(2.6±0.4)、(3.0±0.7)、(3.4±1.3)h,AUC_(0-24h)分别为(3 621.29±1 1 17.37)、(7 492.68±2 031.58)、(13 796.25±4 594.37)μg·h·L(-1),t_(max)分别为(1.8±0.7)、(2.1±0.9)、(1.9±0.4)h,t_(1/2)分别为(2.6±0.4)、(3.0±0.7)、(3.4±1.3)h,AUC_(0-24h)分别为(3 621.29±1 1 17.37)、(7 492.68±2 031.58)、(13 796.25±4 594.37)μg·h·L^(-1),AUC_(0-∞)分别为(3 710.53±1 144.47)、(7 592.98±2 082.12)、(14 074.54±4 870.39)μg·h·L(-1),AUC_(0-∞)分别为(3 710.53±1 144.47)、(7 592.98±2 082.12)、(14 074.54±4 870.39)μg·h·L^(-1)。多次给药100 mg后的药动学参数ρ_(max)为(1 231.83±209.99)μg·L(-1)。多次给药100 mg后的药动学参数ρ_(max)为(1 231.83±209.99)μg·L^(-1),t_(max)为(1.7±0.9)h,t_(1/2)为(3.0±0.8)h,AUC_(0-24h)为(7 043.78±1 818.54)μg·h·L(-1),t_(max)为(1.7±0.9)h,t_(1/2)为(3.0±0.8)h,AUC_(0-24h)为(7 043.78±1 818.54)μg·h·L^(-1),AUC_(0-∞)为(7 131.65±1 840.84)μg·h·L(-1),AUC_(0-∞)为(7 131.65±1 840.84)μg·h·L^(-1)。结论在50(-1)。结论在50²00 mg给药剂量范围内,依普利酮片在体内呈线性动力学特征。     

HPLC-MS/MS法和EMIT法分析人血浆中霉酚酸浓度的相关性

目的:建立高效液相色谱串联质谱法(HPLC-MS/MS)测定人血浆中霉酚酸的浓度,并与酶放大免疫分析法(EMIT)测定的结果进行对比。方法:经霉酚酸治疗的患者血浆样本共111份,以EMIT法进行常规监测后再用HPLC-MS/MS法复测,采用Kolmogorov-Smirnova检验、配对t检验、Pearson相关分析、Passing-Bablok回归法和Bland-Altman一致性限度图研究2种方法测定结果的相关性和一致性,并进行经济学分析。结果:EMIT法和HPLC-MS/MS法测定霉酚酸血浆药物浓度结果的差异有统计学意义,EMIT法检测值(C_EMIT)比HPLC-MS/MS法检测值(C_HPLC-MS/MS)高(27.28±28.62)%,Passing-Bablok回归方程为C_HPLC-MS/MS＝0.931×C_EMIT -0.367,r=0.988。此外,HPLC-MS/MS法检测单个样本的成本比EMIT法低35.4元。结论:该研究建立的HPLC-MS/MS法与EMIT法具有较好的相关性,与EMIT法相比,HPLC-MS/MS法成本低,减轻了患者的经济负担,可替代EMIT法用于霉酚酸的常规监测。     

用HPLC—MS／MS法测定人血浆中的二甲双胍浓度

目的：建立高效液相色谱-质谱／质谱（HPLCMS／MS）联用法测定人血浆中二甲双胍浓度的方法。方法：血浆样品经乙腈沉淀蛋白质后，用HPLC—MS／MS法测定二甲双胍浓度。甲醇-乙腈10mmol／L乙酸铵溶液（20：20：60）为流动相，流速为0．2mL／min；采用大气压化学电离源，以多离子反应监测（MRM）方式进行正离子检测，二甲双胍和内标苯乙双胍的定量分析离子对分别为m／z 130．2→71．0和m／z 206．1→59．9。结果：血浆样品中二甲双胍线性范围为2．0～2000μg／L（n=7，r=0．9996），最低定量限为2．0μg／L。低、中、高（10、500、1500 μg／L）3种浓度的日内RSD分别为4．65％、2．84％和3．41％（n=5）；日间RSD分别为7．96％、3．98％和4．77%（n=5）；准确度为95．9％、97．4％和89．90%（n=5）。结论：本方法灵敏度高、专属性强、重现性好、准确，可用于人血浆中二甲双胍的含量测定。     

HPLC-MS/MS法同时测定柴胡疏肝散水提物中12种主要成分的含量

目的：建立高效液相色谱-串联质谱测定柴胡疏肝散水提物冻干粉中柴胡皂苷（A、B₁、C、D）、橙皮苷、柚皮苷、甘草苷、芍药苷、没食子酸、阿魏酸、槲皮素和异甘草素含量的方法。方法：采用Welch Ultimate XB-C₁₈色谱柱（2.1 mm×100 mm,5 μm）;流动相组成为A相：乙腈,B相：0.1%甲酸-水;以0.3 mL·min^-1的流速进行梯度洗脱,进样量为10 μL;采用电喷雾离子源（ESI）,负离子模式,以多反应监测方式（MRM）进行定量分析。结果：柴胡疏肝散水提物中的12种成分在检测范围内与峰面积之间的线性关系良好。测定结果表明,每克柴胡疏肝散水提物冻干粉中含：柴胡皂苷A 6.712 mg,柴胡皂苷B₁ 5.810 mg,柴胡皂苷C 16.700 mg,柴胡皂苷D 0.034 mg,橙皮苷101.600 mg,柚皮苷172.000 mg,甘草苷3.300 mg,芍药苷50.483 mg,没食子酸1.870 mg,阿魏酸4.945 mg,异甘草素0.032 mg,槲皮素0.051 mg。结论：本方法灵敏度高,简便可靠,可用于柴胡疏肝散水提物冻干粉中12种主要成分的定量分析,并为建立柴胡疏肝散的质量标准提供方法学基础。     

Modernization of Chinese herbal compound and the high performance liquid chromatography tandem mass spectrometry (HPLC-MS)

Chinese herbal compound is playing an important role on curing human diseases.And it has been a trend that Chinese herbal compound is being used all over the world in 21 century.However,our Chinese herbal compound is facing serious challenge for the lack of canonical system of quality criterion for Chinese herbal compound so it has been a urgent problem to set up the quality control standards and reveal therapeutic basis of Chinese herbal compound.In order to give full play to the advantages of Chinese herbal compound,modern scientific and technological is used to research of Chinese herbal compound,especially the high performance liquid chromatography tandem mass spectrometry(HPLC-MS),because it is high sensitive,rapid,and obtain more information.It is very necessary that HPLC-MS is uesed to elucidate the effective components of basic substances of Chinese Herbal Compound,and endow traditional Chinese medicine with modern scientific connotation.     

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。     

液相串联质谱法测定保健食品中脂溶性维生素方法建立及其应用

摘 要 目的：建立同时测定保健食品中9种脂溶性维生素的液相色谱－质谱联用法。方法: 用适合的有机溶剂充分溶解试样中的脂溶性维生素, 超声提取后,采用Waters ACQUITY UPLC BEH C18 (100 mm×2.1 mm , 1.7 μm)色谱柱分离;以0.1%甲酸的甲醇溶液和0.1%甲酸的水溶液为流动相进行梯度洗脱,通过大气压化学电离源多反应监测(MRM)模式进行检测。结果: 9种脂溶性维生素在相应的浓度范围内线性关系良好(r≥0.99),方法检出限在0.9~38.3 μg/100 g之间。3个添加水平的回收率分别为78.5%~114.9%,RSD为1.57%～11.1%（n=6）。结论: 该方法简便、快速、准确、灵敏,适用于营养补充剂类保健食品中脂溶性维生素的测定。     

大鼠尿中人参皂苷Rd及其代谢物的LC-MS研究

目的探讨人参皂苷Rd在大鼠体内的代谢产物及转化途径。方法选择SD大鼠6只，单剂量口服和静脉给予人参皂苷Rd，分段收集给药前和给药后0～24 h尿样，将尿样分时段合并后采用旋转薄膜蒸发浓缩，以固相萃取小柱纯化处理，采用高效液相色谱-串联飞行时间质谱进行检测。结果通过比较给药前后的TOF总离子流图，对尿中推测的代谢物和标准物质的出峰时间及相关化合物选择离子扫描二级质谱图进行了比较分析，结果在尿中发现了7种代谢产物，系统分析了这些代谢产物的代谢转化规律及可能结构。结论大鼠尿中人参皂苷Rd的主要转化途径为氧化、水解、结合及异构化代谢反应。     

HPLC-MS/MS法测定大鼠血浆中伏立康唑和卡泊芬净及其药动学初步研究

目的 建立高效液相色谱-串联质谱（HPLC-MS/MS）法同时测定大鼠血浆中伏立康唑和卡泊芬净的浓度,并用于伏立康唑和卡泊芬净单独给药和联合给药后SD大鼠体内的药动学初步研究。方法 伏立康唑、卡泊芬净分别以氘代伏立康唑和氘代卡泊芬净为内标,血浆样品经乙腈提取,以0.1%甲酸-乙腈和0.1%甲酸-水为流动相,用Phenomenex SynergiHydro-RP 80A柱进行梯度分离,0.5 mL/min体积流量,柱温为常温,10 μL进样量,多级反应监测（MRM）ESI正离子模式;12只SD大鼠随机分成3组,即伏立康唑（ig,40 mg/kg）组、卡泊芬净（iv,5 mg/kg）组、伏立康唑（ig,40 mg/kg）与卡泊芬净（iv 5 mg/kg）联合给药组,分别于给药后不同时间点颈静脉采血进行浓度测定,并计算药动学参数。结果 伏立康唑在0.5~500.0 ng/mL、卡泊芬净在4~4 000 ng/mL线性关系均良好,批内精密度（RSD%）和准确度（RE%）均小于10%,伏立康唑和卡泊芬净提取回收率均大于90%;SD大鼠单剂量联合给予伏立康唑和卡泊芬净后,伏立康唑消除变快,卡泊芬净的消除变慢;伏立康唑、卡泊芬净的C_max、AUC均高于单独用药。结论 HPLC-MS/MS法的专属性强、灵敏、准确、可靠,可用于测定SD大鼠血浆中伏立康唑和卡泊芬净的浓度及药动学研究。伏立康唑延缓了卡泊芬净在动物体内的消除速度,卡泊芬净通过促进伏立康唑的吸收,增加了其在动物体内的血药浓度,联用后二者生物利用度均提高。     

HPLC-MS/MS法同时检测生物样本中的氯霉素、甲砜霉素及氟甲砜霉素

目的 建立专属灵敏的高效液相色谱-质谱法( HPLC-MS/MS),用于生物样本中的3种常见抗生素氯霉素、甲砜霉素及氟甲砜霉素的微量检测.方法 生物样本(猪肉、猪肝)经一定的方法提取并纯化后,采用高效液相色谱分离3种抗生素,并用电喷雾离子化串联质谱( ESI-MS/MS)进行检测和定量分析.结果 氯霉素在0.1～10 ng·mL-1、甲砜霉素及氟甲砜霉素在10～100 ng·mL-1线性关系良好,回收率＞86％,RSD＜10％.结论 该方法灵敏度高、专属性强,回收率较高、精密度较好,适用于生物样本中的微量氯霉素、甲砜霉素及氟甲砜霉素的检测.     

液质联用技术研究肽类药物药动学中的样品制备技术

肽类药物的研究开发成为新生物技术药物研究开发的热点之一。然而，建立可靠、灵敏和准确的肽类药物体内分析方法是肽类药物临床前和临床药动学研究的难点。样品制备技术是建立符合药动学研究要求的定量分析方法的关键。现综述液质联用技术在肽类药物药动学研究中的样品制备技术方法的目的、要求、特点和分类。结合近年发表的文献具体阐述了固相萃取法、蛋白质沉淀法、超滤离心法、亲和层析法和部分其他方法的原理及其应用实例。     

VND3207及其代谢产物在大鼠体内的药代动力学

目的建立液质联用(HPLC-MS/MS)方法,同时测定血浆中VND3207及其代谢产物的浓度并探讨VND3207在大鼠体内的药代动力学。方法 SD大鼠ig给予VND3207 70 mg.kg-1后,于不同时间点采集血样,血浆样品经C18反相液相色谱柱梯度洗脱,采用串联质谱正离子检测多反应监测模式对VND3207及其代谢产物丁香酸和丁香醇进行定量分析,计算VND3207及其代谢产物的药代动力学参数。结果 VND3207、丁香酸和丁香醇的定量线性范围均为2～2000μg.L-1,最低定量下限为2μg.L-1,日内和日间精密度CV均<15%,准确度为91.2%～110.7%。通过测定SD大鼠ig给予VND3207 70 mg.kg-1后12 h的血药浓度,计算VND3207,丁香酸和丁香醇药时曲线下面积(AUC0-∞)分别为19.37±10.56,1825.32±719.97和(9.89±1.75)mg.L-1.min;消除半衰期(T1/2)分别为78.0±44.6,114.4±17.9和(66.0±23.8)min。结论 建立了快速、灵敏、准确地同时定量大鼠血浆中VND3207,丁香酸和丁香醇液质联用分析方法。VND3207被大鼠快速吸收,其中大量VND3207被氧化为丁香酸,少量被还原为丁香醇。     

HPLC-MS/MS法测定人血浆中阿雷地平及其主要代谢产物的浓度

目的建立高效液相色谱-质谱联用法(HPLC-MS/MS)定量测定人血浆中阿雷地平及其主要代谢产物羟基阿雷地平的浓度。方法人血浆样品用液液萃取法处理,用Kinetex C₁₈柱(4. 6 mm×100 mm,2. 6μm)色谱柱,以纯水-乙腈溶液为流动相,流速为0. 5 mL·min^-1,用电喷雾离子化源,负离子方式,多反应监测(MRM)扫描方式进行监测。考察该方法的专属性、标准曲线与定量下限、精密度与回收率、基质效应和稳定性。结果血浆中阿雷地平的标准曲线方程为y=4. 45×10^-1x+6. 6×10^-3(r=0. 998 2),在0. 02～10μg·L^-1线性关系良好,定量下限为0. 02μg·L^-1;羟基阿雷地平的标准曲线方程为y=9. 82×10^-1x+1. 70×10^-3(r=0. 996 7),在0. 2～100μg·L^-1线性关系良好,定量下限为0. 2μg·L^-1。2种化合物的日内、日间RSD均<10%,提取回收率为91. 78%～97. 97%,无明显的基质效应。结论本法快速、准确、灵敏度高、重现性好,适用于人体血浆中阿雷地平、羟基阿雷地平浓度的测定,可用于阿雷地平、羟基阿雷地平的药代动力学研究。     

Contact sensitizers modulate the arachidonic acid metabolism of PMA-differentiated U-937 monocytic cells activated by LPS

For the effective induction of a hapten-specific T cell immune response toward contact sensitizers, in addition to covalent-modification of skin proteins, the redox and inflammatory statuses of activated dendritic cells are crucial. The aim of this study was to better understand how sensitizers modulate an inflammatory response through cytokines production and COX metabolism cascade. To address this purpose, we used the human monocytic-like U-937 cell line differentiated by phorbol myristate acetate (PMA) and investigated the effect of 6 contact sensitizers (DNCB, PPD, hydroquinone, propyl gallate, cinnamaldehyde and eugenol) and 3 non sensitizers (lactic acid, glycerol and tween 20) on the production of pro-inflammatory cytokines (IL-1β and TNF-α) and on the arachidonic acid metabolic profile after bacterial lipopolysaccharide (LPS) stimulation. Our results showed that among the tested molecules, all sensitizers specifically prevent the production of PMA/LPS-induced COX-2 metabolites (PGE_2, TxB₂ and PGD₂), eugenol and cinnamaldehyde inhibiting also the production of IL-1β and TNF-α. We further demonstrated that there is no unique PGE₂ inhibition mechanism: while the release of arachidonic acid (AA) from membrane phospholipids does not appear do be a target of modulation, COX-2 expression and/or COX-2 enzymatic activity are the major steps of prostaglandin synthesis that are inhibited by sensitizers. Altogether these results add a new insight into the multiple biochemical effects described for sensitizers.     

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。