Development of a simple method for simultaneous determination of tazarotene and betamethasone dipropionate and their metabolites using LC–MS method and its application to dermatopharmacokinetic study

In our study, a method for the determination for tazarotene and betamethasone dipropionate in human tissue‐engineered skin was established. Tazarotene gel, betamethasone dipropionate cream or a combination cream was administered to the skin. Then the skin was taken off at 0.25, 0.75, 1.75, 3, 5, 8, 12, 24, 36, 48 h time points after the residual drug was removed. The concentrations of tazarotene, betamethasone dipropionate and their major metabolites in skin were determined by LC–MS. Tazarotene and tazarotenic acid were detected in the concentration range of 2–200 μg/mL with an LLOQ of 2 μg/mL. Betamethasone dipropionate was detected in the concentration range 0.5–300 μg/mL with an LLOQ of 0.5 μg/mL, and betamethasone was detected at 2–200 μg/mL with an LLOQ of 2 μg/mL. The intra‐ and inter‐day precisions of the four analytes in the skin homogenate were all <15% (RSD, %). The results showed that tazarotene could be metabolized to tazarotenic acid and betamethasone dipropionate could be metabolized to betamethasone in tissue‐engineered skin. The results also revealed that this method was suitable for the simultaneous determination of tazarotene, betamethasone dipropionate and their metabolites in tissue‐engineered skin.     

液相色谱-串联质谱法测定尿液中7种有机磷酸酯代谢物

利用液相色谱-三重四极杆质谱(LC-MS/MS)联用技术,建立了人尿液中7种有机磷酸酯代谢产物-有机磷酸二酯的检测方法.针对不同理化性质的有机磷酸二酯,采用固相萃取技术进行富集净化,筛选出高效的固相萃取柱,并对其洗脱条件进行优化;同时,对流动相和质谱参数进行优化,获取用于各代谢产物定性与定量分析的特征离子对.研究结果表明,前处理采用Oasis WAX固相萃取柱富集、2 mL含5%氨水的甲醇和2 mL甲醇洗脱目标物,除磷酸二乙酯(DEP,17.8%~36.2%)外,其余目标化合物回收率均在60.5%~104.0%之间.在优化的液相色谱条件下,7种化合物可达到完全基线分离.7种有机磷酸二酯的检测限和定量限分别在0.005~0.2μg/L和0.02~0.5μg/L之间,日内和日间精密度结果(RSD≤15.4%)表明,本方法具有较好的稳定性和重现性.本方法用于普通人群尿液中有机磷酸二酯的检测,7种化合物在尿液中均有检出,总浓度在0.5~6.7μg/L之间.     

Simultaneous quantitative analysis of phosphocreatine,creatine and creatinine in plasma of children by HPLC–MS/MS method: Application to a pharmacokinetic study in children with viral myocarditis

A simple and rapid HPLC–MS/MS method was developed and validated for simultaneous measurement of phosphocreatine and its metabolites creatine and creatinine in children's plasma. A 50 μL aliquot of plasma was prepared by protein precipitation with acetonitrile–water (1000 μL, 1:1, v/v) followed by separation on a Hypersil Gold C₁₈ column (35°C) with gradient mobile phase consisting of 2 mm ammonium acetate aqueous solution (pH 10) and methanol at a flow rate of 0.3 mL/min and analyzed by mass spectrometry in both positive (phosphocreatine) and negative (creatine and creatinine) ion multiple reaction monitoring mode. Good linearity (r > 0.99) was obtained for the three analytes. The intra‐day and inter‐day values of CV were <5.46% (?13.09% ≤ RE ≤ 2.57%). The average recoveries of the three analytes were 70.9–97.5%. No obvious impact was found for the quantitation of three analytes in normal, hemolyzed and hyperlipemic plasma. In the end, this method was successfully applied to a pharmacokinetic study of phosphocreatine in children (six cases) with viral myocarditis of children after intravenous infusion of 2 g of the test drug. The pharmacokinetc parameters of phosphocreatine/creatine were as follows: t_1/2 0.24/0.83 h, T_max 0.49/0.55 h, C_max 47.34/59.29 μg/mL, AUC_last 17.07/59.63 h μg/mL, AUC_inf 17.16/79.01 h μg/mL and MRT 0.29/0.67 h.     

Quantification of docetaxel and its main metabolites in human plasma by liquid chromatography/tandem mass spectrometry

Docetaxel is an antineoplastic agent widely used in therapeutics. The objective of this study was to develop and validate a routine assay, using liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS), for the simultaneous quantification of docetaxel and its main hydroxylated metabolites in human plasma. A structural analogue, paclitaxel, was used as the internal standard. Determination of docetaxel and four metabolites (M1, M2, M3 and M4) was achieved using only 100 microL of plasma. Liquid-liquid extraction was used for sample preparation, with extraction efficiency of at least 90% for all analytes. Detection used positive-mode electrospray ionization in selected reaction monitoring mode. The lower limit of quantification (LLOQ) was 0.5 ng/mL for all analytes. The assay was linear in the calibration curve range 0.5-1000 ng/mL and acceptable precision and accuracy (<15%) were obtained with concentrations above the LLOQ. This method was sufficiently selective and sensitive for quantification of metabolites in plasma from cancer patients receiving docetaxel chemotherapy, and is suitable for routine analyses during pharmacokinetic studies.     

固相萃取-超高效液相色谱-串联质谱法测定人尿中苯氧乙酸除草剂和有机磷、拟除虫菊酯农药代谢物北大核心CSCD

基于96孔固相萃取-超高效液相色谱-串联质谱法,建立了人尿中2种苯氧乙酸除草剂、2种有机磷农药代谢物和4种拟除虫菊酯农药代谢物的测定方法。通过对液相色谱条件、质谱条件和样品前处理过程的系统优化,实现了在16 min内对8种目标分析物的分析测定。具体方法:1 mL尿液经β-葡萄糖醛酸酶酶解过夜,Oasis HLB 96孔固相萃取进行目标分析物的提取净化,甲醇洗脱;以0.1%(体积分数)乙酸乙腈和0.1%(体积分数)乙酸水作为流动相,Acquity BEH C_(18)作为分析柱进行色谱分离;负离子电喷雾(ESI-)多反应监测(MRM)模式下检测目标化合物,同位素内标法定量。2,4-二氯苯氧乙酸(2,4-D)、2,4,5-三氯苯氧乙酸(2,4,5-T)2种苯氧乙酸除草剂和3-苯氧基苯甲酸(3-PBA)、4-氟-3-苯氧基苯甲酸(4F-3PBA)、反式二氯乙烯基二甲基环丙烷羧酸(trans-DCCA)3种拟除虫菊酯农药代谢物在0.1~100μg/L内、对硝基苯酚(PNP)、3,5,6-三氯-2-吡啶酚(TCPY)2种有机磷农药代谢物、顺式二氯乙烯基二甲基环丙烷羧酸(cis-DCCA)1种拟除虫菊酯代谢物在0.2~100μg/L内线性关系良好,相关系数均大于0.9993;方法检出限为0.02~0.07μg/L,方法定量限为0.08~0.2μg/L;低、中、高3个水平下的加标回收率为91.1%~110.5%,日内精密度为2.9%~7.8%,日间精密度为6.2%~10%。应用该方法测定了214份尿液样本。结果显示除2,4,5-T外,其余7种目标分析物均有检出。TCPY、PNP、3-PBA、4F-3PBA、trans-DCCA、cis-DCCA、2,4-D的检出率为2.8%~99.1%。检出浓度(中位值)由高到低分别是2.0μg/L(TCPY)、1.8μg/L(PNP)、0.99μg/L(trans-DCCA)、0.81μg/L(3-PBA)、0.44μg/L(cis-DCCA)、0.35μg/L(2,4-D)和未检出(4F-3PBA)。该方法操作简便,定量准确,灵敏度高,每批次可完成96个样品测定,适用于人尿中多种农药及农药代谢物的批量分析测定。     

Simultaneous LC‐MS/MS bioanalysis of etoposide and paclitaxel in mouse tissues and plasma after oral administration of self‐microemulsifying drug‐delivery systems

In this study, a liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method was developed and validated to simultaneously determine the anticancer drugs etoposide and paclitaxel in mouse plasma and tissues including liver, kidney, lung, heart, spleen and brain. The analytes were extracted from the matrices of interest by liquid–liquid extraction using methyl tert‐butyl ether–dichloromethane (1:1, v/v). Chromatographic separation was achieved on an Ultimate XB‐C₁₈ column (100 × 2.1 mm, 3 μm) at 40°C and the total run time was 4 min under a gradient elution. Ionization was conducted using electrospray ionization in the positive mode. Stable isotope etoposide‐d3 and docetaxel were used as the internal standards. The lower limit of quantitation (LLOQ) of etoposide was 1 ng/g tissue for all tissues and 0.5 ng/mL for plasma. The LLOQ of paclitaxel was 0.4 ng/g tissue and 0.2 ng/mL for all tissues and plasma, respectively. The coefficients of correlation for all of the analytes in the tissues and plasma were >0.99. Both intra‐ and inter‐day accuracy and precision were satisfactory. This method was successfully applied to measure plasma and tissue drug concentrations in mice treated with etoposide and paclitaxel‐loaded self‐microemulsifying drug‐delivery systems.     

Glycidyl fatty acid esters in food by LC-MS/MS: method development

An improved method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the analysis of glycidyl fatty acid esters in oils was developed. The method incorporates stable isotope dilution analysis (SIDA) for quantifying the five target analytes: glycidyl esters of palmitic (C16:0), stearic (C18:0), oleic (C18:1), linoleic (C18:2) and linolenic acid (C18:3). For the analysis, 10 mg sample of edible oil or fat is dissolved in acetone, spiked with deuterium labelled analogs of glycidyl esters and purified by a two-step chromatography on C18 and normal silica solid phase extraction (SPE) cartridges using methanol and 5% ethyl acetate in hexane, respectively. If the concentration of analytes is expected to be below 0.5 mg/kg, 0.5 g sample of oil is pre-concentrated first using a silica column. The dried final extract is re-dissolved in 250 μL of a mixture of methanol/isopropanol (1:1, v/v), 15 μL is injected on the analytical C18 LC column and analytes are eluted with 100% methanol. Detection of target glycidyl fatty acid esters is accomplished by LC-MS/MS using positive ion atmospheric pressure chemical ionization operating in Multiple Reaction Monitoring mode monitoring 2 ion transitions for each analyte. The method was tested on replicates of a virgin olive oil which was free of glycidyl esters. The method detection limit was calculated to be in the range of 70-150 μg/kg for each analyte using 10 mg sample and 1-3 μg/kg using 0.5 g sample of oil. Average recoveries of 5 glycidyl esters spiked at 10, 1 and 0.1 mg/kg were in the range 84% to 108%. The major advantage of our method is use of SIDA for all analytes using commercially available internal standards and detection limits that are lower by a factor of 5-10 from published methods when 0.5 g sample of oil is used. Additionally, MS/MS mass chromatograms offer greater specificity than liquid chromatography-mass spectrometry operated in selected ion monitoring mode. The method will be applied to the survey of glycidyl fatty acid esters in food products on the Canadian market.     

同位素稀释-高效液相色谱-质谱联用技术检测大鼠血浆中的芥子气水解产物

应用同位素稀释-高效液相色谱-质谱联用技术(LC-MS/MS),建立了同时定量检测血浆中芥子气水解代谢产物硫二甘醇(TDG)和二羟乙基亚砜(TDGO)的方法.应用甲醇和乙腈混合溶剂沉淀染毒大鼠血浆中蛋白,采用ZORBAX-C18色谱柱(100 mm×3.0 mm,3.5μm),以5 mmol/L甲酸铵-甲醇梯度洗脱分离待测物.以d8-TDG为内标,在正离子多反应监测模式下定性和定量分析TDG和TDGO.方法学验证结果表明,TDG在5～800 μg/L和TDGO在0.5～80.0 μg/L范围内均呈良好的线性关系(r2＞0.991),定量限分别为5和0.5 μg/L,加标回收率在101％～118％之间,方法的日内和日间精密度(RSD)均小于10％.对SD大鼠(n=6)采用皮下注射方式进行染毒后采样测定,代谢动力学参数计算结果显示,TDG和TDGO的达峰时间(tmax)分别为30和60 min,峰值浓度(cmax)为(1724±227)μg/L和(301±115)μg/L,血浆浓度-时间曲线下面积(AUC)为(3286±249) μg· h/L和(1010±363) μg· h/L.     

悬浮固化-分散液液微萃取-液相色谱-串联质谱测定纺织废水中磷系阻燃剂

建立了悬浮固化-分散液液微萃取结合液相色谱-串联质谱测定纺织废水中5种痕量磷系阻燃剂的方法。通过对萃取过程中萃取剂、分散剂的种类与体积、盐浓度、溶液pH值等对萃取效率的影响因素优化,确立了最佳萃取条件。采用了密度小于水的十一烷醇（400 μL）为萃取剂,甲醇（300 μL）为分散剂,控制溶液pH值在6~9之间,NaCl添加量为2 g,萃取时间为涡旋2 min。在优化的萃取条件下,该方法在2~100 μg/L均有良好的线性关系,相关系数大于0.995,除二（2,3-二溴丙基）磷酸酯（BIS）的检出限为5 μg/L外,三（2-氯乙基）磷酸酯（TCEP）、三（1,3-二氯-异丙基）磷酸酯（TDCP）、三（1-氮丙啶基）氧化膦（TEPA）和三（2,3-二溴丙基）磷酸酯（TRIS）的检出限均为2 μg/L。后整理、染色和印花等实际废水样品加标试验表明,方法的平均回收率为71.6%~114.5%,RSD为2.7%~11.2%（n=6）。对11个样品进行检测,其中3个废水样品检出TCEP与TDCP化合物,含量为2.6~3.4 μg/L。本方法简单,快速,灵敏度好且环保绿色,能够对纺织废水中的5种痕量磷系阻燃剂进行准确的定性与定量检测。     

Liquid chromatography–tandem mass spectrometry method for simultaneous determination of cyclosporine A and its three metabolites AM1, AM9 and AM4N in whole blood and isolated lymphocytes in renal transplant patients

A LC‐MS/MS method was developed and validated for the determination of cyclosporine A (CsA) and its three phase 1 metabolites AM1, AM9, and AM4N in whole blood and lymphocytes isolated on the Histopaque gradient. 200 μL of whole blood was precipitated with 10 mol/L zinc sulfate in acetonitrile/methanol (40:60, v/v) and lymphocytes isolated from 1.5 mL blood were extracted with acetonitrile/methanol (40:60, v/v). The analytes and internal standard cyclosporine D were separated on RP column BEH C18, 2.1×50 mm, 1.7 μm using gradient LC‐MS/MS analysis in positive electrospray mode. Time of analysis was 5 min. Linearity in blood was 5–2000 μg/L for CsA, AM1, and AM9; 2–500 μg/L for AM4N; and 2–500 μg/L for all substances in lymphocytes. Coefficient of variations was 1.8–9.8% and recovery was 92.0–110.0%. The method was used in early and chronic renal transplant patients for therapeutic drug monitoring of CsA to compare either its share in lymphocytes as target organ or binding to one lymphocyte. The same parameters were calculated for all metabolites tested.     

加速溶剂萃取-固相萃取/超高效液相色谱-串联质谱法测定育苗基质中矮壮素与助状素

研究建立了一种加速溶剂萃取-固相萃取/超高效液相色谱-串联质谱法（SPE-UPLC-MS/MS）测定育苗基质中矮壮素和助状素的分析方法。样品采用快速溶剂萃取仪（ASE）提取,经CBA弱阳离子交换柱净化后,在亲水作用色谱柱上用SeQuant ZLC-HILIC MEKCK色谱柱进行分离;电喷雾正离子（ESI+）模式电离,多反应监测（MRM）模式检测。矮壮素和助状素的质量浓度在0.2~10 μg/kg范围内线性关系良好（r2>0999）,在2、5、10 μg/kg加标水平的平均回收率分别为77%~106%和97%~111%,相对标准偏差（RSD）分别为7.3%~21.7%和5.6%~16.1%,检出限（LOD）均为0.02 μg/kg,定量下限（LOQ）均为0.1 μg/kg。该方法简便、快速、灵敏、准确,适合育苗基质中矮壮素和助状素残留的确证和定量测定。     

Determination of levetiracetam in human plasma by liquid chromatography/electrospray tandem mass spectrometry and its application to bioequivalence studies

The first liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the determination of levetiracetam, an antiepileptic drug, in human plasma is described. The plasma filtrate obtained after solid-phase extraction (SPE), using a polymer-based, hydrophilic-lipophilic balanced (HLB) cartridge, was submitted directly to a short column LC/MS/MS assay. There was no significant matrix effect on the analysis. For validation of the method, the recovery of the free analytes was compared to that from an optimized extraction method, and the analyte stability was examined under conditions mimicking sample storage, handling, and analytical procedures. The extraction procedure yielded extremely clean extracts with a recovery of 79.95% and 89.02% for levetiracetam and the internal standard (IS), respectively. The intra-assay and inter-assay precision for the samples at the lower limit of quantitation (LLOQ) were 6.33 and 6.82%, respectively. The calibration curves were linear for the dynamic range of 0.5 to 50 microg/mL with a correlation coefficient r >/= 0.9971. The intra-assay accuracy at LLOQ, LQC, MQC, and HQC levels ranged from 81.60 to 95.40, 93.00 to 103.47, 95.97 to 104.09, and 91.15 to 95.18%, respectively, while the inter-assay accuracy at LLOQ, LQC, MQC and HQC levels varied from 80.20 to 95.40, 88.53 to 107.53, 95.97 to 108.45, and 91.15 to 112.70%, respectively. The method is rugged and fast with a total instrumental run time of 2 min. The method was successfully applied for bioequivalence studies in human subject samples after oral administration of 1000 mg immediate release (IR) formulations.     

Simultaneous determination of cyadox and its metabolites in plasma by high‐performance liquid chromatography tandem mass spectrometry

Cyadox is a novel antimicrobial growth‐promoter of the quinoxalines. For food safety and pharmacokinetic studies, a convenient, sensitive and reproducible LC‐ESI‐MS/MS method was developed for the simultaneous determination of cyadox and its major metabolites, quinoxaline‐2‐carboxylic acid, 1,4‐bisdesoxycyadox, cyadox‐1‐monoxide and cyadox‐4‐monoxide in chicken plasma. Plasma sample was subjected to a simple deproteinisation with acetonitrile. Analysis was performed on a C₁₈ column by detection with mass spectrometry in multiple reaction monitoring mode. A gradient elution program with 0.2% formic acid, methanol and acetonitrile was performed at a flow rate of 0.2 mL/min. The decision limits (CCαs) of five analytes in plasma ranged from 1.0 to 4.0 μg/L, and the detection capabilities (CCβs) were <10 μg/L. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. The extraction recoveries of five analytes were between 87.4 and 93.9% in plasma at the spiked levels of 5 (10)–200 μg/L with the relative standard deviations <10% for each analyte. The developed method demonstrated a satisfactory applicability in real plasma samples.     

Dispersive liquid-liquid microextraction and gas chromatography-mass spectrometry determination of polychlorinated biphenyls and polybrominated diphenyl ethers in milk

An effective multi‐residue pretreatment technique, solid‐phase extraction (SPE) combined with dispersive liquid–liquid microextraction (DLLME), was proposed for the trace analysis of 14 polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in milk samples using gas chromatography–mass spectrometry (GC‐MS). Interesting analytes in milk samples were extracted with hexane after protein precipitation. The hexane extracts were loaded on an LC‐Florisil column to isolate analytes from the milk matrix. The elutes were dried and dissolved in acetone, which was used as the disperser solvent in subsequent DLLME procedures. The effects of several important parameters on the extraction efficiency were evaluated. Under the optimized conditions, a linear relationship was obtained in the range of 0.02–10.00 μg/L (PCBs) and 0.5–100.00 μg/L (PBDEs). The LOD (S/N=3) and relative standard deviations (RSDs, n=5) for all analytes were 0.01–0.4 μg/L and 0.6–8.5%, respectively. The recoveries of the standards added to raw bovine milk samples were 74.0–131.8%, and the repeatabilities of the analysis results were 1.12–17.41%. This method has been successfully applied to estimating PCBs and PBDEs in milk samples.     

在线净化液相色谱-串联质谱法快速测定牛奶中的6种孕激素

建立了在线净化液相色谱-串联质谱同时测定牛奶中炔诺酮、17α-羟基孕酮、甲羟孕酮、乙酸甲地孕酮、孕酮和醋酸美伦孕酮6种孕激素的方法。本方法采用乙腈为提取溶剂提取目标化合物。提取液经在线净化柱Cyclone-P净化,经Phenyl-Hexyl色谱柱分离,流动相采用0.5%（v/v）甲酸水溶液-乙腈,在电喷雾正离子模式下以多反应监测（MRM）方式测定,内标法定量。方法在0.1~50 μg/L范围内呈线性关系,线性相关系数均大于0.999。6种分析物的测定低限为0.5 μg/kg,在牛奶中3个水平的添加回收率在90.8%~107.5%之间,相对标准偏差在6.3%~11.8%之间。该方法快速简便,灵敏度高,选择性好,可用于牛奶样品中孕激素的快速定性定量分析。     

Simultaneous determination of cyclophosphamide, ifosfamide, doxorubicin, epirubicin and daunorubicin in human urine using high-performance liquid chromatography/electrospray ionization tandem mass spectrometry: bioanalytical method validation

A reversed-phase high-performance liquid chromatography (rp-HPLC) system interfaced with an electrospray ionization (ESI) source coupled to tandem mass spectrometry (MS/MS) was developed and validated for the determination of cyclophosphamide (CP), ifosfamide (IF), daunorubicin (DNR), doxorubicin (DXR), and epirubicin (EPI) in human urine. The analysis of samples containing multiple analytes with a dissimilar range of polarities was carried out using a conventional reversed-phase chromatographic BDS Hypersil C8 column. The analytical run was 15 min. The triple quadrupole mass spectrometer was operated in positive ion mode and multiple reaction monitoring (MRM) was used for drug quantification. The method was validated over a concentration range of 0.2 to 4.0 microg.L(-1) for CP, IF, DXR, EPI and 0.15-2.0 microg.L(-1) for DNR in human urine. The lower limit of quantification (LLOQ) was 0.2 microg.L(-1) for CP, IF, EPI and was set at 0.3 and 0.15 microg.L(-1) for DXR and DNR, respectively. The relative standard deviations (RSD%) were <11.2% for inter- and intra-day precisions. The overall accuracy was also within 114.7% for all analytes at the concentrations of the quality control samples. The potential of ionization suppression resulting from the endogenous biological material on the rp-HPLC/MS/MS method was evaluated and measured. The feasibility of the proposed HPLC/ESI-MS/MS procedure was demonstrated by analyzing urine samples from pharmacy technicians and nurses working in hospitals or personnel employed in drug-manufacturing plants.     

A rapid MCM‐41 dispersive micro‐solid phase extraction coupled with LC/MS/MS for quantification of ketoconazole and voriconazole in biological fluids

A rapid dispersive micro‐solid phase extraction (D‐μ‐SPE) combined with LC/MS/MS method was developed and validated for the determination of ketoconazole and voriconazole in human urine and plasma samples. Synthesized mesoporous silica MCM‐41 was used as sorbent in d ‐μ‐SPE of the azole compounds from biological fluids. Important D‐μ‐SPE parameters, namely type desorption solvent, extraction time, sample pH, salt addition, desorption time, amount of sorbent and sample volume were optimized. Liquid chromatographic separations were carried out on a Zorbax SB‐C₁₈ column (2.1 × 100 mm, 3.5 μm), using a mobile phase of acetonitrile–0.05% formic acid in 5 mm ammonium acetate buffer (70:30, v /v). A triple quadrupole mass spectrometer with positive ionization mode was used for the determination of target analytes. Under the optimized conditions, the calibration curves showed good linearity in the range of 0.1–10,000 μg/L with satisfactory limit of detection (≤0.06 μg/L) and limit of quantitation (≤0.3 μg/L). The proposed method also showed acceptable intra‐ and inter‐day precisions for ketoconazole and voriconazole from urine and human plasma with RSD ≤16.5% and good relative recoveries in the range 84.3–114.8%. The MCM‐41‐D‐μ‐SPE method proved to be rapid and simple and requires a small volume of organic solvent (200 μL); thus it is advantageous for routine drug analysis.     

搅拌棒吸附子萃取与GC-MS法测定水中20种有机氯农药

建立了搅拌棒吸附子萃取/气相色谱-质谱法(SBSE/GC-MS)同时检测水中α-六六六、γ-六六六、β-六六六、七氯、δ-六六六、艾氏剂、环氧七氯、γ-氯丹、顺-氯丹、硫丹Ⅰ、p,p-滴滴伊、狄氏剂、异狄氏剂、p,p-滴滴滴、硫丹Ⅱ、p,p-滴滴涕、异狄氏剂醛、硫丹硫酸盐、甲氧滴滴涕、异狄氏剂酮20种有机氯农药含量的方法.样品在室温下经拌棒吸附子搅拌吸附,甲醇解吸附后,以J&W DB-35 MS(30 m×0.25 mm×0.25 μm)石英毛细管色谱柱为分析柱,气相色谱-质谱选择离子流模式检测.考察了萃取时间、氯化钠及甲醇加入量等对萃取的影响.实验结果表明:在2.5 ～20.0 μg/L 范围内,20种有机氯农药呈良好的线性关系,检出限(S/N=3)为0.008 ～0.118 μg/L,水样中分别添加2.5、20 μg/L的20种有机氯农药,回收率为 52% ～117%,相对标准偏差小于13%(n= 6).该方法操作简便、快速、灵敏度高,应用于实际样品检测,结果满意.     

Liquid chromatography–tandem MS/MS method for simultaneous quantification of paracetamol,chlorzoxazone and aceclofenac in human plasma: An application to a clinical pharmacokinetic study

A facile, fast and specific method based on liquid chromatography–tandem mass spectrometry (LC–MS/MS) for the simultaneous quantitation of paracetamol, chlorzoxazone and aceclofenac in human plasma was developed and validated. Sample preparation was achieved by liquid–liquid extraction. The analysis was performed on a reversed‐phase C₁₈ HPLC column (5 μm, 4.6 × 50 mm) using acetonitrile–10 mM ammonium formate pH 3.0 (65:35, v/v) as the mobile phase where atrovastatin was used as an internal standard. A very small injection volume (3 μL) was applied and the run time was 2.0 min. The detection was carried out by electrospray positive and negative ionization mass spectrometry in the multiple‐reaction monitoring mode. The developed method was capable of determining the analytes over the concentration ranges of 0.03–30.0, 0.015–15.00 and 0.15–15.00 μg/mL for paracetamol, chlorzoxazone and aceclofenac, respectively. Intraday and interday precisions (as coefficient of variation) were found to be ≤12.3% with an accuracy (as relative error) of ±5.0%. The method was successfully applied to a pharmacokinetic study of the three analytes after being orally administered to six healthy volunteers.     

液相色谱-串联质谱法测定蔬菜和水果中6种新型酰胺类杀菌剂的残留量

建立了蔬菜、水果中啶酰菌胺、氟啶酰菌胺、环氟菌胺、嘧菌胺、双炔酰菌胺和硅噻菌胺6种新型酰胺类杀菌剂残留量的液相色谱-串联质谱(liquid chromatography-tandem mass spectrometry, LC-MS/MS)检测方法。试样经乙腈提取、Florisil固相萃取柱净化、以乙腈和水为流动相梯度洗脱、结合新型核壳型填料色谱柱(Poroshell 120 EC-C₁₈)分离,采用电喷雾正离子扫描、多反应监测模式质谱检测,外标法定量。结果表明:固相萃取结合新型色谱柱分离解决了酰胺类农药分析中基质效应强的难点问题。6种杀菌剂在0.5~100 μg/L范围内线性关系良好,相关系数(r)≥0.9990;对7种蔬菜及3种水果进行0.5、5和50 μg/kg 3个加标水平的回收试验,回收率为65%~124%,相对标准偏差(RSD, n=5)为1%~18%; 6种杀菌剂的方法检出限(S/N≥3)为0.10~0.17 μg/kg。该净化、分离模式显著降低了蔬菜、水果中6种新型酰胺类农药的基质效应,方法简单准确,可满足蔬菜和水果中啶酰菌胺等6种新型酰胺类杀菌剂残留检测的要求。