Determination of pyridine, 2-picoline, 4-picoline and quinoline from mainstream cigarette smoke by solid-phase extraction liquid chromatography/electrospray ionization tandem mass spectrometry

The present paper describes the development and validation of a new reversed-phase liquid chromatography–electrospray ionization tandem mass spectrometric method (RP-HPLC–ESI-MS/MS) for simultaneous determination of pyridine, 2-picoline, 4-picoline and quinoline from mainstream cigarette smoke. Liquid–liquid extraction followed by solid-phase extraction was applied to extract the target analytes from cigarette smoke. Baseline chromatographic separation was achieved by utilizing a Zorbax SB-Aq (4.6 × 150 mm, 5 μm) column in gradient chromatographic conditions with acetonitrile and ammonium acetate buffer as mobile phases. Popular commercially available Indian brand filtered and non-filtered cigarettes were analyzed using the same method. The identification of each chemical was established by chromatographic retention times, analyte specific fragmentation patterns and relative peak area ratios of two product/precursor ion pairs. The limit of detection of this method ranged from 1.74 to 14.32 ng/cig using an injection volume of 20 μl. The reproducibility of this method is excellent and better standard deviations were obtained compared to literature reported values for these chemicals. RSD value is less than 9% for all analytes.     

Analysis of primary aromatic amines in the mainstream waterpipe smoke using liquid chromatography-electrospray ionization tandem mass spectrometry

In recent years waterpipe smoking has spread worldwide and emerged as global health issue. Yet only little is known on the composition of waterpipe smoke. Here, we present a study on the identification and quantification of primary aromatic amines (PAAs) in this complex environmental matrix. Smoking of the waterpipe was conducted with a smoking machine and particulate matter was collected on glass fiber pads. We developed a fast, simple and specific liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS/MS) approach to simultaneously detect 31 different PAAs in this matrix. The detection limits comprised a range of 0.45-4.50 ng per smoking session, represented by 2-aminobiphenyl and 3,4,5-trichloroaniline, respectively. Intra- and inter-day precision were determined and proved excellent. We detected 31.3 ± 2.2 ng aniline and 28.0 ± 1.6 ng 4,4'-oxydianiline in the smoke of one waterpipe session. The water in the bowl exerted a small but considerable filter effect on PAAs. The method worked-out showed excellent sensitivity and specificity and is thus highly suited for the determination of PAAs in mainstream waterpipe smoke.     

气相色谱-质谱法测定卷烟烟气总粒相物中14种芳香胺

以五氟丙酸酐为衍生化试剂,氘代2-氨基萘和氘代邻甲苯胺为双内标,采用DB-35MS石英毛细管柱(30 m×0.25 mm i.d×0.25 μm d.f)和选择离子模式,建立了卷烟烟气总粒相物中芳香胺的气相色谱-质谱分析方法.该方法检出限在0.03～2.13 ng/cig.之间,加标平均回收率在92.6%～110.4%之间,相对标准偏差在0.18%～6.4%之间.已用该方法测定了某品牌卷烟烟气总粒相物中14种芳香胺.     

高效液相色谱-串联质谱法测定纺织品中的致癌芳香胺

建立了高效液相色谱-串联质谱法(LC/MS/MS)测定纺织品中致癌芳香胺的检测方法.纺织品中的偶氮染料在柠檬酸缓冲液中用连二亚硫酸钠还原为芳香胺,用硅藻土提取还原液中的芳香胺,用乙醚洗脱,浓缩至近干后用甲醇定容.使用液相色谱-串联质谱进行测定,色谱柱为XTerra MS C18柱,流动相为甲醇和0.025 mol/L乙...     

Rapid simultaneous determination of 14 sulfonamides in wastewater by liquid chromatography tandem mass spectrometry

This paper describes a rapid method for the determination of 14 kinds of sulfonamides (SAs) in wastewater using SPE, and LC-MS/MS with positive ESI (ESI(+)) and selected reaction monitoring (SRM) mode. The SPE was performed on an Oasis hydrophilic-lipophilic-balanced (HLB) cartridge. Chromatographic separation on a C18 column was achieved using a binary eluent containing methanol and water with 0.2% formic acid. Typical recoveries of the analytes ranged from 22.3 to 87.0% at a fortification level of 100 ng/L. The LODs in wastewater except sulfathiazole (3 ng/L) could be detected and quantified at levels as low as 1 ng/L. Finally, the method was applied to water from the municipal outlet and the aquaculture wastewater effluent. Sulfamethazine (SM(2)), sulfamethoxypyridazine (SMP), and sulfamethoxazole (SMZ) were most frequently found in wastewater in a concentration range between 1.2 and 31.7 ng/L.     

Determination of flomoxef in human plasma by liquid chromatography/electrospray ionization tandem mass spectrometry

A specific, sensitive, rapid and reproducible method for the determination of flomoxef in human plasma using high‐performance liquid chromatography–tandem mass spectrometry was developed and validated. Flomoxef was detected using an electrospay ionization method operated in negative‐ion mode. Chromatographic separation was performed in gradient elution mode on a Luna® C₁₈(2) column (3 μm , 20 × 4.0 mm) at a flow rate of 1 mL/min and runtime 3.5 min. The mobile phase consisted of acetonitrile and water containing 0.1% formic acid as additive. Extraction of flomoxef from plasma and precipitation of plasma proteins was performed with acetonitrile with an absolute recovery of 86.4 ± 1.6%. The calibration curve was linear with a correlation coefficient of 0.999 over the concentration range 10–5000 ng/mL and the lower limit of quantification was 10 ng/mL. The intra‐ and inter‐day precisions were <11.8%, while the accuracy ranged from 99.6 to 109.0%. A stability study of flomoxef revealed that it could be successfully analyzed at 4ºС over 24 h, but it was unstable in solutions at room temperature during short‐term storage (4 h) and several freeze–thaw cycles. Copyright © 2013 John Wiley & Sons, Ltd.     

Rapid and sensitive liquid chromatography tandem mass spectrometry method for the quantification of ambroxol in human plasma

A sensitive, specific and rapid high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was described and validated for the quantification of ambroxol in human plasma using enalaprilat as the internal standard (IS). Chromatographic separation was performed on a Lichrospher CN column with a mobile phase of methanol and water (containing 0.1% formic acid) (70:30, v/v). The total run time was 5.0 min for each sample. The analytes was detected by mass spectrometry with electrospray ionization source in positive selected reaction monitoring mode. The precursor-fragment ion reaction for ambroxol was m/z 378.9 --> 263.8, and for IS was m/z 349.0 --> 205.9. The linearity was established over the concentration range of 1.56-400.00 ng/mL. The inter-day and the intra-day precisions were all within 10%. A simple protein precipitation with methanol was adopted for sample preparation. The extraction recoveries of ambroxol and IS were higher than 90.80%. The validated method was successfully applied in pharmacokinetic study after oral administration of 90 mg ambroxol to 24 healthy volunteers.     

Determination of bencycloquidium bromide in dog plasma by liquid chromatography with electrospray ionization tandem mass spectrometry

A rapid, selective and sensitive liquid chromatography/tandem mass spectrometry (LC‐MS/MS) method was developed and validated for determining bencycloquidium bromide (BCQB) in beagle dog plasma. The plasma sample was deproteinized with methanol which contained l‐ethyl‐bencycloquidium bromide as internal standard, and supernantant was assayed by LC‐MS/MS. The chromatographic separation was performed on a Phenomenex C₁₈ column (100 × 2.0 mm, i.d., 3.0 μm) with a gradient programme mobile phase consisting of methanol and ammonium acetate (5 mm) containing 0.15% acetic acid and at a flow rate of 0.3 mL/min. Electrospray ionization in positive ion mode and selective reaction monitoring was used for the quantification of BCQB with a monitored transitions m/z 330.2 → 142.1 for BCQB and m/z 344.2 → 126.2 for IS. Validation results indicated that the lower limit of quantification was 0.05 ng/mL and the assay exhibited a linear range of 0.05–10.0 ng/mL and gave a correlation coefficient of 0.9998. The intra‐ and inter‐run precisions of the assay were 1.7–4.6 and 3.2–15.6%, respectively, and the intra‐ and inter‐day accuracies were ?8.8 to 1.1 and ?5.0 to 4.6%, respectively. The developed method was applied for the pharmacokinetic study of BCQB in beagle dogs following a single intranasal dose. Copyright © 2009 John Wiley & Sons, Ltd.     

A sensitive method for determination of salvianolic acid A in rat plasma using liquid chromatography/tandem mass spectrometry

Salvianolic acid A (SAA), a major effective constituent of Salvia miltiorrhizas, is widely used in traditional Chinese medicine. A sensitive rapid analytical method was established and validated for SAA in rat plasma, which was further applied to assess the pharmacokinetics of SAA in rats receiving a single oral dose of SAA. The method used liquid chromatography tandem mass spectrometry in multiple reaction monitoring mode with chloramphenicol as the internal standard. A simple liquid-liquid extraction based on ethyl acetate was employed. The combination of a simple sample cleanup and short chromatographic run time (3 min) increased the throughput of the method substantially. The method was validated over the range 1.4-1000 ng/mL with a correlation coefficient >0.99. The lower limit of quantification was 1.4 ng/mL for SAA in plasma. Intra- and inter-day accuracies for SAA were 95-113 and 98-107%, and the inter-day precision was less than 12%. This method is more sensitive and faster than previous methods. After a single oral dose of 100 mg/kg of SAA, the mean peak plasma concentration (Cmax) of SAA was 318 ng/mL at 0.5 h, the area under the plasma concentration-time curve (AUC0-12 h) was 698 +/- 129 ng.h/mL, and the elimination half-life (T1/2) was 3.29 h.     

Development and validation of a sensitive method for simultaneous determination of rosuvastatin and N‐desmethyl rosuvastatin in human plasma using liquid chromatography/negative electrospray ionization/tandem mass spectrometry

A sensitive and specific liquid chromatography tandem mass spectrometric method was developed and validated for the simultaneous determination of rosuvastatin (ROS) and N‐desmethyl rosuvastatin (NOR‐ROS) in human plasma using deuterium‐labeled internal standards. The plasma samples were prepared using liquid–liquid extraction with diethyl ether. Chromatographic separation was accomplished on an Xterra MS C₁₈ column. The mobile phase consisted of a gradient mixture of 15 µmol/L ammonium acetate in water and in methanol, maintained at a flow rate of 0.4 mL/min. Mass spectrometric detection was carried out in negative electrospray ionization mode and monitored by quantification and qualification transitions for each analyte. Using 300 μL plasma samples, the lower limits of quantification of ROS and NOR‐ROS were 0.05 and 0.02 µg/L respectively. The linearity of ROS and NOR‐ROS ranged from 0.05 to 42 and 0.02 to 14 µg/L respectively. The relative standard deviations of ROS and NOR‐ROS were <13 and 9%, respectively, while the deviations from expected values were within ?4.7–9.8 and ?5.2–4.6%, respectively. The present method offered high sensitivity and was successfully applied to a 24 h pharmacokinetic study of ROS and NOR‐ROS in healthy subjects receiving a single dose of 10 mg ROS. Copyright © 2013 John Wiley & Sons, Ltd.     

Gender-dependent pharmacokinetics of olaparib in rats determined by ultra-high performance liquid chromatography/electrospray ionization tandem mass spectrometry

The aim of the present study was to develop a liquid chromatography/electrospray ionization tandem mass spectrometry (LC–ESI–MS/MS) method for the determination of olaparib in rat plasma. The plasma samples were processed using one-step protein precipitation with acetonitrile and then separated on Waters Acquity BEH C₁₈ column (50 × 2.1 mm, particle size 1.7 μm) using water containing 0.1% formic acid and acetonitrile as mobile phase with optimized gradient elution. Mass spectrometric detection was carried out by selective reaction monitoring mode via positive ESI mode with precursor-to-product transitions of m/z 435.3 > 367.1 and m/z 443.1 > 375.2 for olaparib and ²H₈-olaparib (internal standard). The method was linear over the concentration range 0.1–2000 ng/ml with correlation coefficient >0.9987. The lower limit of quantitation was 0.1 ng/ml. The method showed excellent accuracy and precision, negligible matrix effect and high extraction recovery. The validated method was subsequently utilized to determine the concentration of olaparib in rat plasma and further applied to the pharmacokinetic study of olaparib in rat plasma. Our results demonstrated that olaparib showed gender-dependent pharmacokinetics in rats. Compared with that in males, olaparib showed high plasma exposure, long half-life, low clearance and high bioavailability in females.     

Rapid quantification of lisinopril in human plasma by liquid chromatography/tandem mass spectrometry

An assay based on protein precipitation and liquid chromatography/tandem mass spectrometry (LC-MS/MS) has been developed and validated for the quantitative analysis of lisinopril in human plasma. After the addition of enalaprilat as internal standard (IS), plasma samples were prepared by one-step protein precipitation using perchloric acid followed by an isocratic elution with 10 mm ammonium acetate buffer (pH adjusted to 5.0 with acetic acid)-methanol (70:30, v/v) on a Phenomenex Luna 5 mu C(18) (2) column. Detection was performed on a triple-quadrupole mass spectrometer utilizing an electrospray ionization (ESI) interface operating in positive ion and selected reaction monitoring (SRM) mode with the precursor to product ion transitions m/z 406 --> 246 for lisinopril and m/z 349 --> 206 for enalaprilat. Calibration curves of lisinopril in human plasma were linear (r = 0.9973-0.9998) over the concentration range 2-200 ng/mL with acceptable accuracy and precision. The limit of detection and lower limit of quantification in human plasma were 1 and 2 ng/mL, respectively. The validated LC-MS/MS method has been successfully applied to a preliminary pharmacokinetic study of lisinopril in Chinese healthy male volunteers.     

A generic stepwise optimization strategy for liquid chromatography electrospray ionization tandem mass spectrometry methods

The feasibility and advantages of using sophisticated chemometric tools in combination with the execution of thoroughly planned experiments to determine experimental conditions for optimal performance of an LC-ESI-MS/MS analysis is demonstrated. A stepwise strategy is proposed, which provides a controlled optimization procedure of the chromatographic quality (in terms of separation among the sample constituents) and maximizes the mass spectrometric signal of the selected product ions. Design of experiments (DOE) and response surface methodology are applied throughout the procedure. The stepwise approach has the advantage of dealing with the different optimization criteria separately, i.e. first ensuring sufficient chromatographic separation, then maximizing the amount of precursor ion entering the mass spectrometer, and finally generating high amounts of selected product ions. The experiments are performed on a linear ion trap mass spectrometer. Retention mapping using the band-tracking model is applied during LC development, which facilitates the optimization of segmented gradients. A set of different siderophores, strong iron chelates, is used as the model substances.     

A sensitive and specific liquid chromatography/tandem mass spectrometry method for determination of echinacoside and its pharmacokinetic application in rats

A rapid and sensitive method based on liquid chromatography/tandem mass spectrometry (LC/MS/MS) for the determination of echinacoside in rat plasma was established and fully validated. A single step of liquid–liquid extraction with n‐butanol was utilized. Chromatographic separation of the analyte and the internal standard (IS), chlorogenic acid, from the sample matrix was performed using a Capcell‐MG C₁₈ analytical column (100 2.0 mm × 5 µm), with a gradient of acetonitrile and water containing 0.1% acetic acid as the mobile phase. Detection was performed on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization source operated in negative ion selected reaction monitoring mode. The method was linear in the concentration range 10–2500 ng/mL. The deviations of both intra‐ and inter‐day precisions (RSD) were 7.1% and the assay accuracies were within 99.2–106.5%. Echinacoside proved to be stable during sample storage, preparation and analysis when an antioxidant solution was used. The method was successfully applied to a pharmacokinetic study in rats after an intragastric administration of echinacoside (100 mg/kg). With the lower limit of quantification at 10 ng/mL, this method proved to have sufficient selectivity, sensitivity and reproducibility for the pharmacokinetic study of echinacoside. Copyright © 2009 John Wiley & Sons, Ltd.     

Determination of ethyl glucuronide in hair samples by liquid chromatography/electrospray tandem mass spectrometry

A method for the determination of ethyl glucuronide (EtG) in hair samples, using liquid chromatography/electrospray tandem mass spectrometry (LC/ESI-MS/MS), was developed and validated. The treatment of hair samples was as follows: to 100 mg of washed (dichloromethane followed by methanol, 1 ml each) and cut (1-2 mm) material, 700 microl of water, 20 microl of internal standard solution (pentadeuterated EtG, D(5)-EtG, 500 microg/l) and 20 microl of methanol were added. Samples were incubated at 25 degrees C overnight and then ultrasonicated for 2 h. Finally, 8 microl of the centrifuged solution (13,000 rpm) were analyzed by LC/ESI-MS/MS in negative ion mode. The surviving ions of EtG and D(5)-EtG were monitored together with the following MRM transitions: m/z 221 --> 75, m/z 221 --> 85 (EtG) and m/z 226 --> 75, m/z 226 --> 85 (D(5)-EtG). The method exhibited a mean correlation coefficient better than 0.9998 over the dynamic range (3-2000 pg/mg). The lower limit of quantification (LLOQ) and the limit of detection (LOD) were 3 and 2 pg/mg respectively. The intra- and interday precision and accuracy were studied at four different concentration levels (3, 5, 56 and 160 pg/mg) and were always better than 7% (n = 5). Matrix effects did not exceed 20%. The method was applied to several hair samples taken from autopsies of known alcoholics, from patients in withdrawal treatment, from social drinkers, from adult teetotalers and from children not exposed to ethanol, with EtG concentrations globally ranging from < or =2 to 4180 pg/mg.     

直接萃取-GC/MS法测定卷烟主流烟气中四种芳香胺

采用气相色谱/质谱法直接测定了卷烟主流烟气中的1-氨基萘、 2-氨基萘、 3-氨基联苯和4-氨基联苯等4种芳香胺.该方法直接用CH2Cl2溶剂超声振荡萃取滤片中的芳香胺,超声萃取的同时加入衍生试剂,使萃取和衍生化同步进行,萃取液过硅酸镁柱进行进一步纯化,然后旋转浓缩后进行GC/MS分析.方法的RSD在1.0%～3.7%之间,加标回收率在92.9%～101.1%之间.     

Development of a sensitive liquid chromatography/tandem mass spectrometry method for the determination of fenofibric acid in rat plasma

A rapid and sensitive LC‐MS/MS method for the quantification of fenofibric acid in rat plasma was developed and validated. Plasma samples were prepared by liquid–liquid extraction with a mixture of N‐hexane–dichloromethane–isopropanol (100:50:5, v/v/v). Isocratic chromatographic separation was performed on a reversed‐phase Discovery C₁₈ column (2.1 × 50 mm, 5 µm). The mobile phase was methanol–water–formic (75:25:0.25, v/v/v). Detection of fenofibric acid and the internal standard (IS) diclofenac acid was achieved by ESI MS/MS in the negative ion mode using m/z 317 → m/z 213 and m/z 294 → m/z 250 transitions, respectively. The method was linear from 0.005 to 1.250 µg/mL when 100 μL plasma was analyzed. The lower limit of quantification was 0.005 µg/mL. The intra‐ and inter‐day precision values were below 8.2%, and accuracy ranged from ?0.9 to 2.1% in all quality control samples. The recovery was 90.3–94.7% and 83.3% for fenofibric acid and IS, respectively. Total run time for each sample analysis was 2.5 min. The validated method was successfully applied to a pharmacokinetic study in six rats after oral administration of fenofibrate, the ester prodrug of fenofibric acid (equivalent to fenofibric acid 5 mg/kg). The method permits laboratory scientists with access to the appropriate instrumentation to perform rapid fenofibric acid determination. Copyright © 2011 John Wiley & Sons, Ltd.     

A sensitive method for determination of furanodiene in rat plasma using liquid chromatography/tandem mass spectrometry and its application to a pharmacokinetic study

Furanodiene, a sesquiterpene component extracted from the essential oil of the rhizome of Curcuma wenyujin Y.H. Chen et C. Ling (Wen Ezhu), is widely used in traditional Chinese medicine. A sensitive analytical method was established and validated for furanodiene in rat plasma, which was further applied to assess the pharmacokinetics of furanodiene in rats receiving a single dose of furanodiene. Liquid chromatography tandem mass spectrometry (LC/MS/MS) in multiple reaction monitoring mode was used in the method and costundide was used as internal standard. A simple protein precipitation based on methanol was employed. The simple sample cleanup increased the throughput of the method substantially. The method was validated over the range of 1–1000 ng/mL with a correlation coefficient >0.99. The lower limit of quantification was 1 ng/mL for furanodiene in plasma. Intra‐ and inter‐day accuracies for furanodiene were 88–115 and 102–107%, and the inter‐day precision less than 14.4%. After a single oral dose of 10 mg/kg of furanodiene, the mean peak plasma concentration of furanodiene was 66.9 ± 23.4 ng/mL at 1 h, the area under the plasma concentration–time curve (AUC_{0–10 h}) was 220 ± 47.8 h ng/mL, and the elimination half‐life was 1.53 ± 0.06 h. After an intravenous adminstration of furanodiene at a dosage of 5 mg/kg, the area under the plasma concentration–time curve was 225 ± 76.1 h?ng/mL, and the elimination half‐life was 2.40 ± 1.18 h. Based on this result, the oral bioavailability of furanodiene in rats at 10 mg/kg is 49.0%. Copyright © 2011 John Wiley & Sons, Ltd.     

LC/MS/MS法同时测定卷烟主流烟气中4种TSNAs

烟草特有亚硝胺（TSNAs）是存在于、烟草制品和卷烟烟气中的一类有害物质。TSNAs在卷烟烟气中的含量很低,卷烟烟气背景复杂,化学成分达3800多种,卷烟烟气中TSNAs的准确定量难度很大。多年来,TSNAs的测量方法随着分析仪器的进步而不断发展,从薄层色谱到GC、LC,从填充柱到毛细管柱,从FID检测到氮磷检测器检测、热能分析仪检测、质谱检测。     

Isothiocyanates as derivatization reagents for amines in liquid chromatography/electrospray ionization–tandem mass spectrometry

The applicability of 3‐pyridyl isothiocyanate, p‐(dimethylamino)phenyl isothiocyanate and m‐nitrophenyl isothiocyanate as the derivatization reagents for amines in high‐performance liquid chromatography/electrospray ionization–tandem mass spectrometry (LC/ESI‐MS/MS) was examined. The generated derivatives of amines with these reagents were favorably separated on the reversed‐phase column and detected by ESI‐MS/MS. The C–N bond of the generated thiourea structure was efficiently cleaved by collision‐induced dissociation and gave the single and intense product ion. Among the three reagents, 3‐pyridyl isothiocyanate was the most suitable as the derivatization reagent with regard to the reactivity to amines and the detection sensitivity. Copyright © 2009 John Wiley & Sons, Ltd.