Rapid Simultaneous Determination of Eight Benzimidazoles in Animal Feed by LC�CMS�CMS

A rapid, sensitive and reliable LC?CMS?CMS method for the determination of eight benzimidazoles in animal feed was developed and validated. Samples were extracted with acidic acetonitrile. The extract was diluted with 0.1% formic acid in water, and analyzed by LC?CMS?CMS on a Waters XBridge? C₁₈ column with acetonitrile/0.1% formic acid in water as mobile phase. The samples were quantified with the matrix standard calibration curve method. Good linearity was obtained for eight benzimidazoles at a concentration of 0.005?C2.5 ??g mL^?1 with a linear relative coefficient more than 0.990. Recoveries of 84.0?C104.0% with CVs of 2.50?C7.50% were obtained. Limit of detection was 2.1?C63.0 ??g kg^?1. The method demonstrated to be suitable for the determination of eight benzimidazoles in animal feed samples.     

LC�CMS�CMS Determination of Gizzerosine in Poultry Feed

A new selective method for the determination of the bioactive amine gizzerosine in poultry feed is presented based on hydrophilic interaction chromatography coupled to electrospray ionisation and tandem quadrupole mass spectrometry. The protonated molecular ions were selected for fragmentation and scanning of the two major product ions using the mass analyser in the multiple reaction monitoring mode. The analytical methodology included acid hydrolysis of feed sample aliquots and desalting and crude clean-up of hydrolysates using cation-exchange chromatography on a polymeric solid-phase extraction sorbent. Mean overall recoveries (n = 9) were 68?C82% in spike-recovery experiments. The limit of detection was 0.25 mg kg^?1. The method was applied to the analysis of fish meal and fish meal-containing poultry feed samples. Although gizzerosine could not be detected in any of the samples, it was found in fish meal made from sand eel after heating to 130 °C for 24 h.     

Uncertainty Analysis of Chlormequat Residue in Fruits by LC�CMS�CMS

A method for determination of chlormequat (CCC) residue in fruits by liquid chromatography?Ctandem mass spectrometry (LC?CMS?CMS) was developed. Residue of CCC was extracted from samples with methanol?Cwater (v/v, 1:1) containing 1.0% acetic acid, cleaned up by strong cationic exchange (SCX) cartridge, and then determined by LC?CMS?CMS. The method showed good linearity over the concentration range 0.002?C5.0 mg kg^?1 with correlation coefficient above 0.997. The limit of detection (LOD) and limit of quantitation (LOQ) for CCC were 5 × 10^?4 mg kg^?1 (S/N = 3) and 0.002 mg kg^?1 (S/N = 10), respectively. Recoveries for CCC at three spiked levels (0.025, 0.050, and 0.20 mg kg^?1) were in the range 80?C102%. Estimation of measurement uncertainty was calculated for CCC at the level of 0.025 mg kg^?1 in fruits. The results demonstrated that the uncertainty of recovery was the main contribution to the combined standard uncertainty. The relative combined standard uncertainties associated with the method ranged from 11 to 13%, depending on the sample matrices.     

Determination of Fulvestrant in Rat Plasma by LC�CMS�CMS: Application to a Pharmacokinetic Study

A reversed-phase liquid chromatography coupled to tandem mass spectrometry (LC?CMS?CMS) method was developed and validated for the determination of fulvestrant in rat plasma. Sample preparation involved a liquid-liquid extraction using 1.0 mL of n-hexane?Cisopropanol (90:10, v/v) to extract the analyte from 0.1 mL of rat plasma. The analytes were separated on a phenyl-based column using the mobile phase consisting of methanol/water containing 5 mM ammonium acetate at the flow rate of 0.3 mL min^?1. The analytes were monitored by tandem mass spectrometry under electrospray negative ionization mode. Linear calibration curves were generated over the fulvestrant concentration ranges of 0.05?C10.0 ng mL^?1 in rat plasma. The accuracy and within- and between-day precisions were within the generally accepted criteria for bioanalytical methods (<15%). This developed and validated assay method was successfully employed to characterize the plasma concentration-time profile of fulvestrant after its intramuscular administration in rats at a dose of 10 mg kg^?1.     

Determination of Pilocarpine in Human Plasma by LC�CAPCI�CMS�CMS and Application to a Pharmacokinetic Study

A sensitive, specific and rapid high performance liquid chromatography?Catmospheric pressure chemical ionization source-tandem mass spectrometry (LC-APCI-MS-MS) method for the determination of pilocarpine in human plasma was developed and validated. The method is based on liquid?Cliquid extraction, followed by a reversed-phase liquid chromatographic separation, and detected by means of tandem mass spectrometry. The linear calibration curve covered a concentration range of 2?C500 ??g L^?1. The intra- and inter-day precisions for pilocarpine were <10% and the accuracies were between 90 and 110%. The method was applied successfully to a pharmacokinetic study involving 20 healthy Chinese male volunteers after oral administration of 6 mg pilocarpine.     

LC�CMS�CMS Quantitative Determination of Gefitinib in Human Serum and Cerebrospinal Fluid

A specific, sensitive, and rapid method based on high-performance liquid chromatography coupled to tandem mass spectrometry (LC?CMS?CMS) was developed for determination of gefitinib in human serum and cerebrospinal fluid (CSF). The analyte was detected by tandem mass spectrometry operating in positive electrospray ionization mode with multiple reaction monitoring (MRM). Gefitinib was extracted from serum or CSF samples with ethyl acetate using icotinib as internal standard. The method was validated over the concentration range of 1.00?C1,000 ng mL^?1 in human serum and 0.05?C50.0 ng mL^?1 in CSF. For both matrices, inter- and intraday precision (CV%) were less than 15% and accuracy was within 85?C115%. Average extraction recoveries were 78.9 and 61.8% in human serum and CSF, respectively. Linearity, recovery, matrix effects, and stability were validated in the two matrices. The method was successfully used for analysis of clinical samples from lung cancer patients with brain metastases treated with gefitinib in the dosage range of 250?C500 mg day^?1.     

Analysis of Biologically Active Constituents in Centella asiatica by Microwave-Assisted Extraction Combined with LC–MS

Centella asiatica (L.) Urban is a traditional herbal medicine used in Asiatic countries, and is commonly used to treat various wounds, leprosy, tuberculosis and lupus diseases. In this work, a new method based on microwave assisted extraction followed by liquid chromatography–diode array detection–electrospray ionization multistage tandem mass spectrometry analysis has been developed for the identification and quantification of biologically active constituents in C. asiatica, including asiatic acid, asiaticoside and madecassoside. The separation was performed on an Agilent Eclipse C₁₈ column (150 mm × 4.6 mm i.d., 5 μm) with gradient elution of acetonitrile and 0.1% aqueous acetic acid within 50 min. Detection was performed at 205 nm. The calibration curves showed good linearity (r ² > 0.9992). The limits of detection ranged from 1.2 to 1.6 μg mL^?1. The intra- and inter-day precision was less than 3% and the recovery of the assay was in the range of 95.4–106.8%. The method was successfully applied to the quantification of the three constituents in different samples of C. asiatica. The results indicated that the developed method could be considered to be a simple, rapid and reliable method for the quality evaluation of C. asiatica. The samples were also analyzed on a liquid chromatography–electrospray ionization–time-of-flight mass spectrometry system to confirm the identification results.     

Determination of Revaprazan in Human Plasma by LC�CMS�CMS and Application to a Pharmacokinetic Study in Chinese Volunteers

A sensitive, specific, and rapid liquid chromatography?Celectrospray ionization?Ctandem mass spectrometry (LC?CESI?CMS?CMS) method was developed for determination of revaprazan in human plasma. Plasma samples were simply treated with methanol to precipitate, and then isolated supernatants were directly injected into the LC?CESI?CMS?CMS system. A Thermo Hypurity C18 column (150 × 2.1 mm, 5 ??m) with mobile phase of methanol?Cwater (70:30, v/v) containing 0.05% formic acid was used for chromatographic separation. Mass-spectrometric quantification was carried out in multiple reaction monitoring (MRM) mode, monitoring the m/z transitions 363.1 ?? 245.1 for revaprazan and 531.2 ?? 489.2 for ketoconazole (internal standard, IS) in positive ion mode. The linear calibration curves covered a concentration range of 2?C1,000 ??g L^?1. The intra- and interday precisions (percentage relative standard deviation, RSD%) for revaprazan at three quality control levels were all <5%, and the accuracies were between 90% and 110%. The method has been successfully applied to a pharmacokinetic study involving 12 Chinese volunteers, and the main pharmacokinetic parameters of revaprazan in Chinese population are reported for the first time.     

Simultaneous Analysis of Selected Typical Antibiotics in Manure by Microwave-Assisted Extraction and LC–MS n

Analysis of antibiotics in the environment has become an urgent issue. A novel method entailing microwave-assisted extraction (MAE) and high-performance liquid chromatography–electrospray mass spectrometry (LC–MS ⁿ ) has been developed for determination of selected typical antibiotics, including quinolones, sulfonamides, and tetracyclines, in manure. Compared with ultrasonic extraction, MAE significantly increased recovery of fluoroquinolones (63–106%), sulfonamides (64–133%), and tetracyclines (64–109%) from manure. Acetonitrile acidified with formic acid buffer solution (pH 4.0) was used for extraction of swine manure whereas chicken manure was extracted with 0.1 M EDTA–McIlvaine buffer solution. Limits of quantification (LOQ) for all compounds were in the range 5.12–168.4 μg kg^?1 dry matter, which were satisfactory for analysis of all samples. The suitability of the method was assessed by analysis of manure from six different sites.     

Determination of Quinine and Doxycycline in Rat Plasma by LC�CMS�CMS: Application to a Pharmacokinetic Study

A fast, sensitive, and specific LC?CMS?CMS method for determination of quinine (QN) and doxycycline (DOX) in rat plasma has been developed and validated. QN, DOX, and cimetidine (internal standard, IS) were extracted from the plasma by protein precipitation. The compounds were separated on a C₁₈ column with methanol?C0.1% aqueous formic acid 70:30 (v/v) as mobile phase at a flow rate of 0.5 mL min^?1 (split 1:3). Detection was by positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode, monitoring the transitions 325.0 ?? 307.0, 445.0 ?? 428.1, and 252.8 ?? 159.0, for QN, DOX, and IS, respectively. The analysis was carried out in 2.0 min and the method was linear in the plasma concentration range 5?C5,000 ng mL^?1. The mean extraction recoveries for QN, DOX, and IS from plasma were 89.4, 90.5, and 86.3%, respectively. The method was validated for linearity, precision, accuracy, specificity, and stability; the results obtained were within the acceptable range. The proposed method was successfully applied to the determination of QN and DOX in rat plasma samples to support pharmacokinetic studies.     

Microwave-Assisted Extraction of Melamine Residues from Pet Food and Analysis by Ion-Exchange LC–DAD

Melamine is attracting much attention because of its toxicity. In the work discussed in this paper, microwave-assisted extraction in combination with ion-exchange high-performance liquid chromatography with diode-array detection was used for analysis of melamine in pet food. Trichloroacetic acid–N,N-dimethylformamide 10:1 was the best extractant, because of the strong polarity of melamine. Separation was performed on a 250 mm × 4.6 mm i.d., 5-μm particle, cation-exchange column; isocratic elution with a mixture of ammonium formate solution (pH 3.0) and acetonitrile was complete within 10 min. UV absorbance DAD detection was performed at 240 nm. Response was a linear function of melamine concentrations from 0.1 to 50 μg mL^?1, with a detection limit of 1.0 mg kg^?1. Intra-day and inter-day precision, as RSD, was <3% and the recovery of the assay was in the range 95.4–106.8%. In analysis of spiked pet food, the new method yielded satisfactory results. Because of its simplicity and accuracy this straightforward method is particularly suitable for routine melamine analysis.     

Determination of Volatile Nitrosamines in Latex Products by HS-SPME�CGC�CMS

Nitrosamines which have been detected in various latex products are carcinogens. The method for determination of volatile nitrosamines in latex products was developed using a combination of headspace solid phase micro-extraction (HS-SPME) and gas chromatography?Cmass spectrometry (GC?CMS). A carboxen/polydimethylsiloxane (CAR/PDMS) fiber was used for HS-SPME involving the following variables: (1) agitation conditions, (2) extraction temperature (3) extraction time, and (4) salt concentration. The instrument performances of three detection systems including GC combined thermal energy analyzer, nitrogen chemiluminescence detector and MS were evaluated. The agitation conditions including magnetic stirring and ultrasonication were investigated by the comparison of extraction efficiency of HS-SPME for nitrosamines. Obtained optimal detection conditions of nitrosamines were HS-SPME at 45 °C for 60 min assisted with magnetic stirring and saturated NaCl followed by GC?CMS. To evaluate this method performance, the commercial products including eleven latex products (gloves, balloons and condoms) and four liquid silicone nipples were analyzed with the method. The results revealed that the method is suitable for simple and effective determination of nitrosamines in latex products. The advantage of this HS-SPME?CGC?CMS method is simple treatment, fast analysis, adequate sensitivity and without organic solvent.     

Simultaneous Determination of Pregabalin, Sildenafil and Its Active Metabolite in Rat Plasma Utilising SPE Followed by LC�CMS�CMS

A sensitive and selective analytical method for the quantification of pregabalin, sildenafil and the active desmethyl metabolite of sildenafil (UK-103320) has been developed. The method can simultaneously quantify the three analytes within the expected in vivo concentration ranges using 50 ??L of rat plasma. It utilises solid-phase extraction followed by high performance liquid chromatography coupled with tandem mass spectrometry. Quantitation in rat plasma demonstrated good accuracy and precision over the following dynamic ranges for each analyte: pregabalin (70?C10,000 ng mL^?1), sildenafil (1?C2,000 ng mL^?1) and UK-103320 (1?C2,000 ng mL^?1). For each analyte, the following lower limits of quantitation were obtained: 70 ng mL^?1 for pregabalin and 1 ng mL^?1 for sildenafil and UK-103320, respectively. The method was successfully used to analyse plasma samples from rats when pregabalin and sildenafil were administered in combination.     

LC�CMS�CMS Quantitative Determination of Brivudine in Human Plasma and Its Application to Pharmacokinetic Studies

A sensitive and specific liquid chromatography?Celectrospray ionization?Ctandem mass spectrometry method has been developed and validated for the identification and quantification of brivudine in human plasma using diclofenac as an internal standard. The method involves extraction with ethyl acetate. The analyte was separated on a C₁₈ column and analyzed in multiple reaction monitoring mode with a negative electrospray ionization interface using the [M?CH]^? ions, m/z 332.8??m/z 80.9 for brivudine, m/z 293.6??m/z 249.5 for diclofenac. The method was validated over the concentration range of 5.54?C2,836 ??g L^?1 for brivudine. The intra-and inter-day precisions were less than 8.91% in terms of relative standard deviation (RSD), and the accuracy was within ?4.22% in terms of relative error (RE). The lower limit of quantification (LLOQ) was 5.54 ??g L^?1 with acceptable precision and accuracy. There were almost no matrix effects. Recovery of brivudine spiked in drug-free plasma was higher than 77.17%. The method was used to study the pharmacokinetic profile of brivudine in human plasma after oral administration of brivudine tablets.     

Multi-Walled Carbon Nanotubes as Matrix Solid-Phase Dispersion Extraction Adsorbent for Simultaneous Analysis of Residues of Nine Organophosphorus Pesticides in Fruit and Vegetables by Rapid Resolution LC�CMS�CMS

A method for simultaneous analysis of residues of nine organophosphorus pesticides in fruit and vegetables has been developed. It involves matrix solid-phase dispersion (MSPD) for preconcentration before rapid resolution liquid chromatography?Ctandem mass spectrometry (RRLC?CMS?CMS). In the MSPD pre-concentration step, the adsorptive performance of multi-walled carbon nanotubes (MWCNT) as MSPD adsorbent and elution with four solvents were investigated; in the LC separation step, a rapid resolution high-throughout LC column was used with gradient elution. The results of the research showed that the linear correlation coefficients (r ²) of the method for the nine target analytes varied between 0.9942 and 0.9996, mean recovery was in the range 71.2?C102.8%, with relative standard deviations (RSD) 2.0?C11.8%, and limits of detection were all below 0.2 ??g kg^?1. The method was used for simultaneous analysis of the nine pesticides in eight different fruit and vegetable samples.     

Determination of Imidol in Rat Plasma by UPLC�CMS�CMS and Its Application in a Pharmacokinetic Study

A rapid, sensitive and accurate ultra-performance liquid chromatography/tandem mass spectrometry method was developed and validated for the quantitative determination of imidol in rat plasma for the first time. The analyte and internal standard were extracted from plasma by liquid?Cliquid extraction with diethyl ether. The separation was performed on a BEH C₁₈ column (50 mm × 2.1 mm, 1.7 ??m). The detection was carried out by electrospray ionization mass spectrometry in positive ion mode with multiple reaction monitoring. Linear calibration curves were obtained in the concentration range of 2.5?C2,500 ng mL^?1, with the lower limit of quantification of 2.5 ng mL^?1. The intra- and inter-day precision (RSD) values were below 8% and accuracy (RE) was from ?7.9 to 6.3%. After strict validation, the method was applied successfully to the pharmacokinetic study of imidol in rats after oral and intravenous administration, respectively.     

Simultaneous Determination of Hydrocodone, and Its Two Metabolites in Human Plasma by HPLC�CMS�CMS

A rapid, sensitive and specific assay method has been developed to simultaneously determine human plasma concentrations of hydrocodone and its metabolites, norhydrocodone, hydromorphone, using high-performance liquid chromatography with an electrospray ionization (ESI) tandem mass spectrometry (HPLC?CMS?CMS). Hydrocodone, its metabolites, and internal standard, hydrocodone-d ₃, norhydrocodone-d ₃, hydromorphone-d ₃, were separated from human plasma using solid-phase extraction (Empore MPC-SD Solid Phase Extraction Disk). The eluate was dried, reconstituted and injected into the LC?CMS?CMS system. Chromatographic separation was performed on a Kromasil 100-5SIL-Dimensions C₁₈ column (100 × 2.1 mm, 5.0 ??m, Thermo Hypersil-Keystone, USA) using a gradient mobile phase with 20 mmol L^?1 ammonium formate in water with 0.2% formic acid and 0.1% formic acid in acetonitrile. Detection and quantitation were performed by MS/MS using electrospray ionization and multiple reactions monitoring in the positive ion mode. The calibration curves were linear over the concentration ranges 0.05?C50 ng mL^?1 for hydrocodone (r ² = 0.9991) and norhydrocodone (r ² = 0.9990), and 0.01?C10 ng mL^?1 for hydromorphone (r ² = 0.9990). The limit of quantification was 0.05 ng mL^?1 for hydrocodone and norhydrocodone, and 0.01 ng mL^?1 for hydromorphone. The extraction recovery was above 64.36, 68.51 and 71.78% for hydrocodone, norhydrocodone and hydromorphone. The accuracy was higher than 99.06, 97.70 and 100.07% for hydrocodone, norhydrocodone and hydromorphone. The intra- and inter-day precisions were <5.80, 5.90 and 3.02% for hydrocodone, norhydrocodone and hydromorphone. The method was accurate, sensitive and simple and was successfully applied to a pharmacokinetic study after a single oral administration of hydrocodone bitartrate at a dose of 5 mg in 12 healthy Chinese volunteers.     

Magnetic Nanoparticle-Based Micro-Solid Phase Extraction and GC�CMS Determination of Oxadiargyl in Aqueous Samples

A new facile, rapid, inexpensive, and sensitive method based on magnetic micro-solid phase extraction (M-??-SPE) coupled to gas chromatography?Cmass spectrometry (GC?CMS) was developed for determination of the herbicide oxadiargyl in environmental water samples. The feasibility of employing non-modified magnetic nanoparticles (MNPs) as sorbent was examined and applied to perform the extraction process. Influential parameters affecting the extraction efficiency along with desorption conditions were investigated and optimized. The limit of detection (LOD, S/N = 3) and limit of quantification (LOQ, S/N = 10) of the method under optimized conditions were 0.005 and 0.030 ng mL^?1, respectively. The relative standard deviations (RSD) (n = 3) at a concentration of 0.10 ng mL^?1 was 11%. The calibration curve of oxadiargyl showed linearity in the range of 0.050?C0.50 ng mL^?1. The developed method was successfully applied to the extraction of oxadiargyl from spiked tap water and Zayande-Rood River water samples and the relative recoveries of 98 and 94% were obtained, respectively.     

Derivatization Method for Determination of Nitrosamines by GC�CMS

Gas chromatography/low-resolution mass spectrometry with electron impact source was applied to detect eight nitrosamines (NAs). NAs were first denitrosated by a mixed solution of hydrobromic and acetic acids, followed by sulfonylation with p-toluenesulfonyl chloride. Variables affecting the denitrosation and sulfonylation, such as temperature, time, pH and reagent concentration, were optimized. Comparison of the determination of NAs with and without derivatization was performed. Results showed that better chromatographic behavior and larger mass response were obtained after derivatization, and instrumental detection limits ranged from 0.016 to 0.053 ng, a nearly 20-fold decrease of those without derivatization. The proposed method provided an alternative to performing accurate qualitative and quantitative analysis of NAs with expensive high-resolution mass spectrometry or thermal energy analyzer.     

On-Line SPE Coupled with LC�CAPCI�CMS for the Determination of Trace Explosives in Water

In this study, a rapid, sensitive, and fully automated on-line solid phase extraction (SPE)?Cliquid chromatography (LC)?Cmass spectrometry (MS) method for the analysis of explosive residues in water, was systematically investigated. First, separation of explosive residues was achieved by reverse-phase chromatography using an XDB-C18 column in 30 min with an eluent containing 0.1% acetic acid, 5 mM ammonium acetate, and methanol. Secondly, atmospheric pressures chemical ionization (APCI) and electrospray ionization (ESI) interfaced with the MS detector were used to examine the explosive residues, indicating that APCI?CMS was more suitable than ESI?CMS for the detection of explosives. Thirdly, the conditions for on-line SPE, including solvent pH and sample injected volume, were optimized. The calibration curves obtained for all explosives studied were linear in the concentration range 0.5?C50 ??g L^?1. The detection limits of this method ranged from 0.05 to 0.5 ??g L^?1 when 4000 ??L of sample was on-line pre-concentrated on C18 enrichment column. The recoveries from lake waters spiked with explosive standard solution ranged from 90.5 to 108.0%. The proposed method is simple, fast, and could be applied successfully to the analysis of explosive residues in contaminated water without any further pretreatment.