Simultaneous determination of salidroside and its aglycone metabolite p-tyrosol in rat plasma by liquid chromatography-tandem mass spectrometry

Salidroside and its aglycone p-tyrosol are two major phenols in the genus Rhodiola and have been confirmed to possess various pharmacological properties. In our present study, p-tyrosol was identified as the deglycosylation metabolite of salidroside after intravenous (i.v.) administration to rats at a dose of 50 mg/kg, but was not detectable after intragastric gavage (i.g.) administration through HPLC-photodiode array detection (PDA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Next, an accurate and precise LC-MS/MS method was developed to quantitatively determine salidroside and p-tyrosol in rat plasma samples. Samples were analyzed by LC-MS/MS on a reverse-phase xTerra MS C18 column which was equilibrated and eluted with an isocratic mixture of acetonitrile-water (1:9, v/v) at a flow rate of 0.3 mL/min. The analytes were monitored by multiple reaction monitoring (MRM) under the negative electrospray ionization mode. The precursor/product transitions (m/z) were 299.0 → 118.8 for salidroside, 137.0 → 118.9 for p-tyrosol and 150.1 → 106.9 for the internal standard (IS), paracetamol, respectively. The calibration curve was linear over the concentration ranges of 50-2,000 ng/mL for salidroside and 20-200 ng/mL for p-tyrosol. The inter- and intra-day accuracy and precision were within ± 15%. The method has been successfully applied to the pharmacokinetic study and the oral bioavailability was calculated.     

Determination of ipriflavone in human plasma by LC-MS and its application in a pharmacokinetic study

A sensitive liquid chromatography-mass spectrometric method was developed for the quantification of ipriflavone in human plasma. The method utilized liquid-liquid extraction of plasma with ethyl acetate. A gradient elution was performed on a Hedera ODS-2 column (150×2.1 mm i.d., 5 μm), using a mobile phase consisting of 0.1% formic acid solution and methanol at a flow rate of 0.5 mL/min. The single quadrupole mass spectrometer was operated in selected-ion monitoring mode via positive electrospray ionization interface detecting m/z 239.1 and 285.1 for ipriflavone and diazepam (the internal standard), respectively. To improve the selectivity and sensitivity, the fragment ion m/z 239.1, which was produced by in-source collision-induced dissociation, was chosen as the quantitative ion for ipriflavone. The method was fully validated and applied to a pharmacokinetic study of ipriflavone. After oral administration of a single 200 mg ipriflavone tablet, the C(max,) AUC(0-72 h) , t(1/2) and T(max) were 6.3±6.3 ng/mL, 80.0±69.1 μg h/L, 23.0±8.6 h and 3.4±2.1 h, respectively.     

A rapid and highly sensitive UPLC-MS-MS method for the quantification of zolpidem tartrate in human EDTA plasma and its application to pharmacokinetic study

A rapid and high sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed and validated for the quantification of zolpidem in human EDTA plasma using ondansetron (IS) as an internal standard. The analyte and IS were extracted from human plasma using ethyl acetate and separated on a C18 column (Inertsil-ODS, 5 μm, 4.6 × 50 mm) interfaced with a triple quadrupole tandem mass spectrometer. The mobile phase, which consisted of a mixture of methanol and 20 mM ammonium formate (pH 5.00 ± 0.05; 75:25 v/v), was injected at a flow rate of 0.40 mL/min. The retention times of zolpidem and IS were approximately 1.76 and 1.22. The LC run time was 3 min. The electrospray ionization source was operated in positive ion mode. Multiple reaction monitoring used the [M + H](+) ions m/z 308.13 → 235.21 for zolpidem and m/z 294.02 → 170.09 for the ondansetron, respectively. Five freeze-thaw cycles was established at -20 and -70°C.The linearity of the response/concentration curve was established in human EDTA plasma over the concentration range 0.10-149.83 ng/mL. The lower detection limit [(signal-to-noise (S/N) > 3] was 0.04 ng/mL and the lower limit of quantification (S/N > 10) was 0.10 ng/mL. This LC-MS-MS method was validated with intra-batch and inter-batch precision of 0.52-8.66.The intra-batch and inter-batch accuracy was 96.66-106.11. Recovery of zolpidem in human plasma was 87.00% and IS recovery was 81.60%. The primary pharmacokinetic parameters were T(max) (h) = (1.25 ± 0.725), C(max) (ng/mL) (127.80 ± 34.081), AUC(0→t), = (665.37 ± 320.982) and AUC(0→∞), 686.03 ± 342.952, respectively.     

Delapril and manidipine measurements by liquid chromatography-tandem mass spectrometry in a pharmaceutical formulation

A simple, specific, fast and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous analysis of delapril (DEL) and manidipine (MAN) from their combination formulation was developed and validated using fesoterodine as the internal standard (IS). The LC-MS/MS method was carried out on a Luna C8 column (50 × 3.0 mm i.d., 3 μm) with a mobile phase consisting of methanol and 10 mmol L(-1) ammonium acetate (90 : 0, v/v), run at a flow rate of 0.25 mL min(-1). The mass spectrometry method was performed employing positive electrospray ionization operating in multiple reaction monitoring mode, monitoring the transitions of m/z 453.1 → 234.1 for DEL, m/z 611.1 → 167.0 for MAN and m/z 412.2 → 223.0 for IS. The total analysis time was 3 min and the method was linear in the concentration range of 6-1080 ng mL(-1) and 2-360 ng mL(-1) for DEL and MAN, respectively. Parameters investigated for the method validation, such as the specificity, linearity, precision, accuracy and robustness, gave results within the acceptable range. Moreover, the proposed method was successfully applied for the simultaneous determination of DEL and MAN and the results were compared to validated liquid chromatography and capillary electrophoresis methods showing non-significant differences (P = 0.9).     

Determination of ligustilide in rat blood and tissues by capillary gas chromatography/mass spectrometry

A gas chromatography/mass spectrometry (GC/MS) method was developed to study the pharmacokinetics of ligustilide following oral administration to rats. The method was used for the analysis of samples taken from rats. Biological samples were prepared by liquid-liquid extraction (LLE) using an n-hexane-ether (2:1) solvent mixture for a sample clean-up step and analyzed by GC/MS with a quadrupole MS detector in selected ion monitoring mode (m/z 190). The calibration curves were linear over the concentration range 0.172-8.60 microg/mL (r > 0.99) for blood samples and a different range (r > 0.99) for different tissue samples. The limit of detection (LOD) was 1.0 ng/mL or 1.0 ng/g (three times the signal-noise ratio). Within- and between-day precision expressed as the relative standard deviation (RSD) for the method was 1.58-3.88 and 2.99-4.91%, respectively. The recovery for all samples was >80%, except for liver samples (>70%). The main pharmacokinetic parameters obtained were: T(max) = 0.65 +/- 0.07 h, C(max) = 1.5 +/- 0.2 microg/mL, AUC = 34 +/- 6 h microg/mL and K(a) = 3.5 +/- 0.6/h. The experimental results showed that ligustilide was easily absorbed, but its elimination was slow, from 3 to 12 h after oral administration. The concentrations of ligustilide in rat cerebellum, cerebrum, spleen and kidney were higher than those in other organs.     

Determination and pharmacokinetics of manidipine in human plasma by HPLC/ESIMS

A sensitive HPLC/ESIMS method was established for the determination of manidipine in human plasma and pharmacokinetics study. After basified plasma with ammonia, manidipine and the internal standard (IS) (felodipine) were extracted with n-hexane and separated on a Hypersil ODS2 column with a mobile phase of methanol-5 mm ammonium acetate solution containing 0.1% acetic acid (85:15, v/v). MS determination was performed by electrospray ionization in the selected ion monitoring mode. Manidipine was monitored at m/z 611.4 and IS at m/z 384. The assay had a calibration range from 0.2 to 20 ng/mL and a lower limit of quantification of 0.1 ng/mL. The method has been successfully applied to the pharmacokinetic study in healthy volunteers.     

高效液相色谱-质谱联用法检测免疫抑制剂及其合并用药

建立高效液相色谱-质谱联用法同时测定人血浆中免疫抑制剂及合并用药12种药物浓度的方法.选用Kromasil-C18色谱柱(50 mm× 4.6 mm×5 μm),以甲醇-乙腈-1mmol/L乙酸铵溶液为流动相,采用梯度洗脱进行分离,样本用甲醇沉淀蛋白后进样,流速:1.1 mL/min;柱温:35℃;进样量:20μL.选用3200QTrap型液相色谱-串联质谱仪的多反应监测(MRM)扫描方式进行检测.12种药物的线性范围为0.2～1000μg/L;定量下限为0.2 μg/L.准确度与精密度结果显示方法日间、日内RSD均小于15％;相对偏差-13％～9.33％,稳定性较好.本方法快速、灵敏,专属性强、重现性好,可用于人体血浆中免疫抑制剂及其常用合并用药共12种药物浓度的测定.     

Determination of sodium cromoglycate in human plasma by liquid chromatography with tandem mass

A sensitive and selective liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of sodium cromoglycate (SCG) in human plasma after a nasal dose of 10.4 mg sodium cromoglycate nasal spray, using pravastatin sodium as the internal standard. The method was validated over a linear range of 0.300-20.0 ng/mL. SCG and I.S. were extracted from 1.0 mL of heparinized plasma by C(18) solid-phase extraction cartridges using methanol as eluting solvent. The dried residue was reconstituted with 100 microL of mobile phase, and 10 microL was injected onto the LC-MS/MS system. Chromatographic separation was achieved on a C(18) column (250 x 4.6 mm i.d., 5 microm particle size) with a mobile phase of methanol-acetonitrile-water (containing 2 mmol/L ammonium acetate; 42.5:42.5:15, v/v/v) at a flow rate of 0.4 mL/min. The analytes were detected with a triple quad LC-MS/MS using ESI with positive ionization. Ions monitored in the multiple reaction monitoring mode were m/z 469.0 (precursor ion) to m/z 245.0 (product ion) for SCG and m/z 447.2 (precursor ion) to m/z327.1 (product ion) for pravastatin sodium (internal standard) The average recovery of SCG from human plasma was 94.88% and the lower limit of quantitation was 0.3 ng/mL. Results from a 3-day validation study demonstrated excellent precision and accuracy across the calibration range of 0.3-20 ng/mL. The method was successfully applied to the pharmacokinetic study of SCG in healthy Chinese volunteers. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Selective and sensitive determination of bis(7)-tacrine, a high erythrocyte binding acetylcholinesterase inhibitor, in rat plasma by high-performance liquid chromatography-tandem mass spectrometry

The current study aims to develop a specific and sensitive LC-MS/MS method for determination of bis(7)-tacrine (B7T) in rat plasma. A 100 microL plasma sample was extracted with ethyl acetate. B7T and the internal standard (IS), pimozide, in the samples were then analyzed with LC-MS/MS in positive electrospray ionization condition. Chromatographic separation of B7T and IS was achieved in a C(18) reversed-phase HPLC column (150 x 2.1 mm i.d.) by isocratic elution with a mobile phase consisting of 0.05% formic acid in water and acetonitrile (1:1, v/v) at a flow rate of 0.35 mL/min. Multiple-reaction monitoring (MRM) mode was employed to measure the ion transitions: m/z 247 to 197 for B7T and m/z 462 to m/z 328 for IS, respectively. The method was linear over the studied ranges of 100-5000 and 10-100 ng/mL. The intra-day and inter-day variations of the analysis were less than 6.8% with standard errors less than 9.0%. The detection limit of B7T in rat plasma was 1 ng/mL. The developed method was successfully applied to the pharmacokinetic study of B7T after intravenous administration of 1 mg/kg B7T and further proved to be readily utilized for determination of B7T in rat plasma samples.     

Rapid and sensitive HPLC-MS/MS method for pharmacokinetic assessment of ribavirin in healthy Chinese

A rapid and sensitive quantitative assay method was developed for determining ribavirin pharmacokinetic in human plasma. The chromatographic separation was achieved within 4.5 min using a SinoChrom ODS-BP column (4.6 x 150 mm, 5 microm) with acetonitrile-water (1 mmol/L ammonium acetate buffer, 0.1% formic acid; 15:85, v/v) at a constant flow rate of 0.8 mL/min. The MRM pairs were m/z 245.2 --> m/z 113.1 for ribavirin and m/z 226.1 --> m/z 152.1 for acyclovir (internal standard), respectively, with dwell times of 200 ms for each transition. The results showed calibration curve for ribavirin was linear over a concentration range of 1-1000 ng/mL. The lower limit of quantification (LLOQ) was 1 ng/mL ribavirin. Twenty healthy volunteers received a 300 mg oral dose of ribavirin. Blood samples were then collected up to 120 h postdosing. All plasma data were comodeled for ribavirin by using noncompartmental modeling. The single dose of ribavirin was well tolerated and no serious adverse effects occurred. The mean time to maximum concentration was about 1.25 h. The mean maximum concentration of drug in plasma for oral ribavirin was 250 ng/mL. The mean elimination half-life was 43.6 h. The present study describes a simple, specific, sensitive HPLC-MS/MS method for measuring plasma drug concentration and analyzing human pharmacokinetics of ribavirin.     

Determination of donepezil hydrochloride (E2020) in plasma by liquid chromatography-mass spectrometry and its application to pharmacokinetic studies in healthy, young, Chinese subjects

A sensitive, simple, and specific liquid chromatographic method coupled with electrospray ionization-mass spectrometry for the determination of donepezil in plasma is developed, and its pharmacokinetics in healthy, male, Chinese is studied. Using loratadine as the internal standard, after extraction of the alkalized plasma by isopropyl alcohol-n-hexane (3:97, v/v), solutes are separated on a C(18) column with a mobile phase of methanol-acetate buffer (pH 4.0) (80:20, v/v). Detection is performed with a time-of-flight mass spectrometer equipped with an electrospray ionization source operated in the positive-ionization mode. Quantitation of E2020 is accomplished by computing the peak area ratio (donepezil [M+H](+) m/z 380-loratadine [M+H](+) m/z 383) and comparing them with the calibration curve (r = 0.9998). The linear calibration curve is obtained in the concentration range 0.1-15 ng/mL. The limit of quantitation is 0.1 ng/mL. The mean recovery of E2020 from human plasma is 99.4% +/- 6.3% (ranging 93.4-102.6%). The inter- and intraday relative standard deviation is less than 15%. After an oral administration of 5 mg E2020 to 20 healthy Chinese volunteers, the main pharmacokinetic parameters of E2020 are as follow: T(max), 3.10 +/- 0.55 h; t((1/2)), 65.7 +/- 12.8 h; C(max), 10.1 +/- 2.02 ng/mL; MRT, 89.4 +/- 13.4 h; and CL/F, 9.9 +/- 4.3 L/h.     

A rapid liquid chromatography-tandem mass spectrometry method for quantification of a biologically active molecule camboginol in the extract of Garcinia cambogia

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of camboginol in the extract of fruit rinds of Garcinia cambogia has been developed. Separation was achieved isocratically on an RP C(18) column using a solvent system consisting of a mixture of acetonitrile-water (9:1) and methanol-acetic acid (99.5:0.5) in the ratio of 30:70 as mobile phase at a flow rate of 0.4 mL/min. A multiple reaction monitoring (MRM) method was developed for quantification of camboginol in the fruit rinds extract of G. cambogia using MRM transitions of m/z 601.4 --> m/z 176.7 and m/z 601.4 --> m/z 448.9, respectively. The calibration curve based on peak area against concentration was linear up to 50 ng/mL with a detection limit of 0.5 ng/mL. The method showed satisfactory reproducibility with a coefficient of variation of less than 6%. The method was successfully applied for quantification of camboginol in different Garcinia extracts.     

Rapid liquid chromatography-tandem mass spectrometry method for quantification of ziprasidone in human plasma

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of ziprasidone (ZIP) in human plasma was developed. ZIP and N-methyl ziprasidone as internal standard (IS) were extracted from alkalinized plasma using tert- butyl methyl ether. Separation was performed isocratically on a C8 column with 90% acetonitrile containing 2 mmol/L ammonium acetate as a mobile phase with a total run time of 2.5 min. MS/MS transitions of m/z 413 --> 194 and m/z 427 --> 177 of the analyte and internal standard were used for quantification. Confirmatory ions of m/z 413 --> 177 and m/z 427 --> 180 were collected as well. The calibration curve based on peak-area ratio was linear up to at least 200 ng/mL with a detection limit of 0.1 ng/mL. The method showed satisfactory reproducibility with a coefficient of variation of less than 5%. The method was successfully applied to the analysis of ZIP in spiked human plasma.     

液相色谱-串联质谱检测蔬菜和茶叶中吡虫啉的残留量

介绍了利用液相色谱-串联质谱（LC-MS/MS）快速、准确地测定蔬菜、茶叶产品中吡虫啉残留量的方法。前处理方法为用乙腈提取,再用弗罗里硅土和活性炭混合柱净化。用多反应监测技术确定吡虫啉的两对离子(m/z 256.0/209.3,m/z 256.0/175.2)为定性离子对,m/z 209.3为定量离子。方法的定量限为0.01 mg/kg,线性范围为0.01～0.5 mg/L,加标回收率为76%～90%,相对标准偏差（RSD）为7.4%～11.0%。     

高效液相色谱串联质谱法测定牛奶中的高氯酸盐

建立了高效液相色谱-串联质谱测定牛奶中高氯酸盐的方法.样品经1%乙酸-乙腈(体积比1:4)混合溶液提取,于6 000 r/min离心20 min后,经0.2μ m的尼龙滤膜、On-GuardⅡRP柱、On-GuardⅡAg柱和On-GuardⅡBa柱净化,最大反相性能色谱柱C12(Synergi 4u MAX-RP 8...     

液相色谱-四极杆-飞行时间质谱法快速筛查与确证紫甘蓝中415种农药残留

应用液相色谱-四极杆-飞行时间质谱(LC-QTOF/MS)建立了一次进样可同时对紫甘蓝中415种农药残留进行快速筛查和准确确证的分析方法。实验采用1%(v/v)醋酸乙腈溶液提取,无水硫酸镁和氯化钠进行盐析,ZORBAX SB-C18色谱柱(100 mm×2.1 mm, 3.5 μm)分离,以0.1%(v/v)甲酸水溶液(含5 mmol/L乙酸铵)-乙腈为二元流动相进行梯度洗脱,应用LC-QTOF/MS在电喷雾电离、全离子MS/MS(All Ions MS/MS)扫描正模式下进行检测,基质匹配外标法定量分析。通过优化全自动MS/MS采集模式(Auto MS/MS)和全离子MS/MS采集模式下的不同参数,得到每种采集模式下的最佳条件。然后在2种不同采集模式的最佳条件下对比,最终选取All Ions MS/MS采集模式。实验结果表明,采用所建立的分析方法可以准确定性和定量筛查紫甘蓝中415种农药残留,所有415种农药在各自的范围内线性相关系数(r²)均大于0.990,其中411种农药的筛查限(SDL)≤5 μg/kg, 413种农药的定量限(LOQ)≤10 μg/kg。在1倍、2倍和10倍LOQ添加水平下,农药的回收率分别为65.7%~118.4%、72.0%~118.8%和70.2%~111.2%,相对标准偏差分别为0.9%~19.7%、0.2%~19.9%和0.6%~19.9%。将该方法应用于2019年欧盟能力验证项目的紫甘蓝样品中未知农药残留筛查方法和定量方法考核样的检测,所有添加农药均被准确定性筛查和定量检测,没有假阳性和假阴性。结果表明,该方法快速、准确、可靠,适用于对紫甘蓝中多种农药残留的高通量定性筛查和准确定量,可以扩展到其他果蔬基质中多农残的高通量筛查。     

Rapid and sensitive determination of udenafil in plasma by LC-MS/MS for intranasal pharmacokinetic study in rats

A rapid and sensitive analytical method for udenafil in rat plasma was developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This chromatographic procedure was then applied to the in vivo pharmacokinetic studies in rats for determining the advantages of intranasal administration of the drug over oral administration. Using liquid-liquid extraction (LLE), udenafil and the internal standard (IS) sildenafil were extracted with dichloromethane from 100 μl of plasma samples. Chromatographic separation was performed using Pursuit XRS C?? column (50 mm × 2.1 mm, i.d., 3 μm, Varian Inc., CA, U.S.A.) with an isocratic mobile phase consisting of acetonitrile and 10 mM ammonium acetate (90 : 10, v/v) at a flow rate of 0.2 ml/min over a total run time of 2.5 min. Detection and quantification was performed by mass spectrometry using the multiple reaction-monitoring mode at m/z 517.4→283.1 for udenafil and m/z 475.3→100.0 for IS. Results showed that the developed method was sensitive and specific for udenafil. Linearity was obtained in the range of 0.5-1000 ng/ml. The coefficient of variation of both intra- and inter-day validation were below 11.6% and the intra- and inter-day accuracy ranged from 91.5 to 109.9%. Udenafil concentration was successfully measured from plasma after intranasal as well as after intravenous or oral administration at clinical dose (1.67 mg/kg) in rats. Moreover, the T(max) values obtained from pharmacokinetic studies suggested that administration of udenafil intranasally could be more effective than by the oral route.     

Validated LC-MS/MS method for quantification of gabapentin in human plasma: application to pharmacokinetic and bioequivalence studies in Korean volunteers

A sensitive validated liquid chromatography-tandem mass spectrometric method (LC-MS/MS) for gabapentin (GB) in human plasma has been developed and applied to pharmacokinetic (PK) and bioequivalence (BE) studies in human. In a randomized crossover design with a 1-week period, each subject received a 300 mg GB capsule. The procedure involves a simple protein precipitation with acetonitrile and separated by LC with a Gemini C(18) column using acetonitrile-10 mm ammonium acetate (20:80, v/v, pH 3.2) as mobile phase. The GB and internal standard [(S)-(+)-alpha-aminocyclohexanepropionic acid hydrate] were analyzed using an LC-API 2000 MS/MS in multiple reaction monitoring mode. The ionization was optimized using ESI(+) and selectivity was achieved using MS/MS analysis, m/z 172.0 --> 154.0 and m/z 172.0 --> 126.0 for GB and IS, respectively. The assay exhibited good linearity over a working range of 20-5000 ng/mL for GB in human plasma with a lower limit of quantitation of 20 ng/mL. No endogenous compounds were found to interfere with the analysis. The accuracy and precision were shown for concentrations over the standard ranges. This method was successfully applied for the PK and BE studies by analysis of blood samples taken up to 36 h after an oral dose of 300 mg of GB in 24 healthy volunteers.     

Development and validation of a highly sensitive LC-MS/MS method for quantitation of dexlansoprazole in human plasma: application to a human pharmacokinetic study

A highly sensitive, specific and simple LC-MS/MS method was developed for the simultaneous estimation of dexlansoprazole (DEX) with 50 μL of human plasma using omeprazole as an internal standard (IS). The API-4000 LC-MS/MS was operated under multiple reaction-monitoring mode using electrospray ionization. A simple liquid-liquid extraction process was used to extract DEX and IS from human plasma. The total run time was 2.00 min and the elution of DEX and IS occurred at 1.20 min. This was achieved with a mobile phase consisting of 0.2% ammonia-acetonitrile (20:80, v/v) at a flow rate of 0.50 mL/min on an X-terra RP 18 (50 × 4.6 mm, 5 μm) column. The developed method was validated in human plasma with a lower limit of quantitation of 2 ng/mL for DEX. A linear response function was established for the range of concentrations 2.00-2500.0 ng/mL (r > 0.998) for DEX. The intra- and inter-day precision values for DEX met the acceptance criteria as per FDA guidelines. DEX was stable in the battery of stability studies, viz. bench-top, auto-sampler and freeze-thaw cycles. The developed assay method was applied to an oral bioequivalence study in humans.     

Liquid Chromatography-Electrospray Quadrupole Linear Ion Trap Mass Spectrometric Method for Quantitation of Domperidone in Chinese Healthy Volunteers

A rapid,sensitive,and accurate method based on LC/MS/MS was developed and validated for the determination of domperidone in human plasma.Domperidone and internal standard,tramadol,were extracted from plasma with diethyl ether-dichloromethane(60∶40,volume ratio)and separated by reversed-phase HPLC with methanol-water-ammonia solution(80∶20∶0.2,volume ratio)as the mobile phase.Detection was carried out via multiple-reaction monitoring(MRM)on a Q-trapTM LC/MS/MS system(Q-trapTM).The assay result was linear over a concentration range of 0.1-30 ng/mL with a limit of quantitation(LOQ)of 0.1 ng/mL.The inter-and intra-day precision levels were within 7.52% and 12.9%,respectively,whereas the accuracy was within a range of 87.3%-114%.This method has been successfully applied to evaluate the pharmacokinetics of domperidone in Chinese healthy volunteers given an oral dose of 10 mg.