Applications of LC/ESI-MS/MS and UHPLC/Qq-TOF-MS for the determination of 141 pesticides in tea

This paper presents the applications of LC-electrospray ionization (ESI)/MS/MS and ultra-HPLC (UHPLC)/ESI quadrupole (Qq)-time-of-flight (TOF) MS for the determination of 141 pesticides in tea. Pesticides were extracted and cleaned up from tea with a modified quick, easy, cheap, effective, rugged, and safe method using graphitized carbon black and primary-secondary amine sorbents. Quantification was achieved using matrix-matched standard calibration curves with isotopically labeled standards or a chemical analog as internal standards in an analytical range from 5 to 500 microg/kg. The LC/ESI-MS/MS served as a reliable tool to quantify the pesticides due to its superior sensitivity and good repeatability. Its method performance characteristics that include overall recovery, intermediate precision, and measurement uncertainty were evaluated according to a statistically designed experiment, i.e., a nested design. About 87% of the pesticides had recoveries between 81 and 110%; 94% had an intermediate precision < or = 20%; and 90% showed measurement uncertainty < or = 40%. About 92% of the pesticides were able to be detected at 5 microg/kg with an S/N > or = 3. The UHPLC/Qq-TOF-MS showed much less sensitivity and poorer repeatability compared to the LC/ESI-MS/MS, and, therefore, it was primarily used for confirmatory purposes based on the accurate mass measurement and isotopic patterns.     

Determination of spiramycin and neospiramycin antibiotic residues in raw milk using LC/ESI‐MS/MS and solid‐phase extraction

A simple confirmatory method for the determination of spiramycin and its metabolite neospiramycin in raw milk using LC ESI MS/MS is presented. Macrolide residues in raw milk were extracted by ACN, and sample extracts were further cleaned up and concentrated using SPE cartridges. Both spiramycin and neospiramycin were protonated in electrospray positive ion mode to form singly and/or doubly charged pseudomolecular ions. Data acquisition was achieved using multiple reaction monitoring, i.e., two transitions, for quantification and confirmation. Matrix‐matched standard calibration curves were utilized to achieve the best accuracy for the method. The method performance was evaluated according to both a conventional validation procedure and a designed experimental result. The measurement uncertainty arising from accuracy and precision was estimated. The method accuracy, expressed as a percentage of an overall recovery, was from 82.1 to 108.8%, and its intermediate precision was less than 20%. LC/ESI‐MS/MS method LODs (S/N ? 3:1) of spiramycin and neospiramycin were less than 1.0 μg/kg.     

Determination of dodine in fruit samples by liquid chromatography electrospray ionization-tandem mass spectrometry

A rapid and sensitive LC/electrospray ionization-MS/MS method has been developed for the determination of dodine in fruit samples. Based on a liquid-liquid extraction of 10 g solid fruit homogenate using an acetone-dichloromethane-hexane mixture and acetate ammonium buffer (pH 4.5), this LC/MS/MS procedure was characterized by recoveries above 50%, with good intra-assay precision (RSD < 13%) and interassay precision (RSD < 18%) for seven different matrixes (apple, apricot, cherry, peach, pear, plum, and quince). This method was validated from 5 to 500 microg/kg according to standard guidelines. Its LOD (1 microg/kg) and LOQ (5 microg/kg) were in accordance with recommendations of the European legislation defined for infant food [maximum residue level (MRL) = 10 microg/kg]. The whole procedure was finally tested on 1022 fruit samples intended for commercialization, both infant food samples and samples not intended in particular for babies. In this study, dodine was detected in 27 samples; none exhibited a concentration higher than the MRL.     

Applications of LC/ESI-MS/MS and UHPLC QqTOF MS for the determination of 148 pesticides in fruits and vegetables

This paper presented the applications of liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) and ultra-high-pressure liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC QqTOF MS) for the determination of 148 pesticides in fruits and vegetables. Pesticides were extracted from fruits and vegetables using a buffered QuEChERS method. Quantification was achieved using matrix-matched standard calibration curves with isotopically labeled standards or a chemical analog as internal standards in an analytical range from 5 to 500 μg/kg. The method performance parameters including overall recovery, intermediate precision, and measurement uncertainty were evaluated according to a statistically designed experiment, i.e., a nested design. For LC/ESI-MS/MS, 95% of the pesticides had recoveries between 81% and 110%; 97% had an intermediate precision ≤20%; and 95% (in fruits) or 93% (in vegetables) showed measurement uncertainty ≤40%. Compared to LC/ESI-MS/MS, UHPLC QqTOF MS showed a relatively poor repeatability and large measurement uncertainty. About 93% (in fruits) or 94% (in vegetables) of the pesticides had recoveries between 81% and 110%; 86% (in fruits) or 90% (in vegetables) had an intermediate precision ≤20%; and 79% (in fruits) or 88% (in vegetables) showed measurement uncertainty ≤40%. LC/ESI-MS/MS proved to be the first choice for quantification or pre-target analysis due to its superior sensitivity and good repeatability. UHPLC QqTOF MS provided accurate mass measurement and isotopic patterns, and was an ideal tool for post-target screening and confirmation.     

Determination of three natural pesticides in processed fruit and vegetables using high-performance liquid chromatography/tandem mass spectrometry

This paper describes a method for the sensitive and selective determination of two macrocyclic lactones (abamectin and spinosad) and azadirachtin in apple purée, concentrated lemon juice, tomato purée and canned peas. The general sample extraction-partitioning method for our gas chromatography and liquid chromatography multiresidue methods has been used. The analytical procedure involves an extraction with acetone and liquid-liquid partitioning with ethyl acetate/cyclohexane combined in one step. The extracts are analyzed by liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) without any further clean-up step. The pesticides are separated on a reversed-phase C12 column using a gradient elution. Thirteen simultaneous MS/MS transitions of precursor ions were monitored. Studies at fortification levels of 2.5-10 microg/kg and 25-100 microg/kg gave mean recoveries ranging from 70-100% for all compounds with satisfactory precision (relative standard deviation (RSD) from 3-20%). The excellent selectivity and sensitivity allows quantification and identification of low levels of pesticides in canned peas, tomato and apple purées (limits of quantitation (LOQs) 1-5 microg/kg) and in concentrated lemon juice (LOQs 2-10 microg/kg). The quantification of analytes was carried out using the most sensitive transition for every compound and by 'matrix-matched' standards calibration.     

Validated procedure for simultaneous trace level determination of the anti-cancer agent gemcitabine and its metabolite in human urine by high-performance liquid chromatography with tandem mass spectrometry

A sensitive, accurate and reproducible procedure has been developed for the quantitative determination of gemcitabine (2',2'-difluorodeoxycytidine, dFdC) and its metabolite 2',2'-difluorodeoxyuridine (2dFdU) in human urine. The samples (2 mL) were extracted by solid-phase extraction (SPE) and analyzed by reversed-phase high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS), operating in multiple reaction monitoring (MRM mode). This procedure was validated using 2'-deoxycytidine as internal standard (IS). The urine assay was linear over the range 0-50 microg/L, with a limit of quantification (LLOQ) of 0.2 microg/L for gemcitabine and 1.0 microg/L for the metabolite. The respective limits of detection (LODs) for dFdC and 2dFdU were 0.05 and 0.3 microg/L. The precision and accuracy of the assay were determined on three different days. The within-series precision was found to be always less than 8.5 and 12.7% for gemcitabine and 2dFdU, respectively. The overall precision expressed as relative standard deviation (CVr) was always less than 7.1% for both analytes. The recovery of gemcitabine was always greater than 90% with a CVr <6.3%. The measurement uncertainty determined from the validation data assessed the possibility of determining this drug and its metabolite at trace levels in urine, considering that the combined uncertainty of the whole procedure was always less than 30%.     

A sensitive confirmatory method for aflatoxins in maize based on liquid chromatography/electrospray ionization tandem mass spectrometry

A liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method for measurement of aflatoxins B1, B2, G1, and G2 in maize is described. Aflatoxins (AFs) were extracted from 1 g samples by using tri-portions of acetonitrile/water (80:20, v/v) (10 + 7 + 7 mL), and 2/5 of the extract diluted to 500 mL by water was cleaned up with a 100 mg Carbograph-4 cartridge. After the addition of the internal standard AFM1, the final extract was analyzed by LC/ESI-MS/MS in positive ion mode using multiple reaction monitoring with a triple-quadrupole instrument. A C(18) column thermostatted at 45 degrees C with a mobile phase gradient of acetonitrile/water with 2 mmol/L ammonium formate was used. Although the matrix suppression effect was negligible, quantitation was achieved by an external calibration procedure using matrix-matched standard solutions to improve accuracy. Sample recoveries at four spiking levels ranged from 81 to 101% (relative standard deviation (RSD) 相似文献   

Determination of pesticide residues in honey by single-drop microextraction and gas chromatography

A novel, simple, and rapid single-drop microextraction (SDME) procedure combined with GC has been developed, validated, and applied for the determination of multiclass pesticide residues in honey samples. The SDME was optimized using a Plackett-Burman screening design considering all parameters that may influence an SDME procedure and a consequent central composite design to control the parameters that were found to significantly influence the pesticide determination. The developed analytical method required minimal volumes of organic solvents and exhibited good analytical characteristics with enrichment factors ranging from 3 for alpha-endosulfan to 10 for lindane, procymidone, and captan and method quantification limits ranging from 0.03 microg/kg for phosalone to 10.6 microg/kg for diazinon. The relative recoveries obtained ranged from 70.8% for captan to 120% for fenarimol, and the precision (RSD) ranged from 3 to 15%. The proposed SDME procedure followed by GC with an electron capture detector for quantification and GC/MS for identification was applied with success to the analysis of 17 honey samples. Monitoring results indicated a low level of honey contamination by diazinon, chlorpyrifos-ethyl, procymidone, bromopropylate, and endosulfan (alpha-, beta-, and endosulfan sulfate) residues that were far below the maximum residue limit values specified by the European Union for endosulfan (10 microg/kg) and bromopropylate (100 microg/kg) in honey samples.     

固相萃取-液相色谱-质谱/质谱法同时测定蜂蜜中的多类药物残留

建立了采用固相萃取-液相色谱-质谱/质谱(SPE-LC-MS/MS)对蜂蜜中磺胺类、硝基咪唑类、喹诺酮类、大环内酯类、林可酰胺类和吡喹酮共计6大类54种药物残留同时测定的方法。蜂蜜经磷酸盐缓冲溶液(pH 8)稀释,Oasis HLB固相萃取柱净化后,通过液相色谱-质谱联用技术进行检测(正离子方式,多反应监测模式)。采用同位素稀释内标法或外标法进行定量,线性关系良好,相关系数大于0.992。方法的定量限(LOQ,以信噪比(S/N)大于10计)分别为磺胺类和硝基咪唑类药物1.0 μg/kg,喹诺酮类和林可酰胺类药物2.0 μg/kg,大环内酯类药物3.0 μg/kg,吡喹酮0.3 μg/kg。总体回收率为32.6%～114%,相对标准偏差为1.3%～28.9%。该方法的定量限满足目前国内外药物的最大残留限量要求,可作为蜂蜜中相关药物残留量的筛选检测方法。     

Application of positive ion chemical ionisation and tandem mass spectrometry combined with gas chromatography to the trace level analysis of ethyl carbamate in bread

A rapid, sensitive and selective method has been developed and validated for the analysis of the contaminant ethyl carbamate (EC) in bread products at the part-per-billion level. The new procedure uses positive ion chemical ionisation (PICI) and tandem mass spectrometry (MS/MS), combined with gas chromatography (GC), on a 'bench-top' triple-quadrupole mass spectrometer. Ammonia was the PICI reagent gas of choice because of its ability to produce abundant [M+H]+ and [M+NH4]+ ions from EC and deuterium-labelled EC (LEC) used as an internal standard. For identification and quantification, selected reaction monitoring (SRM) was used to follow the precursor-to-product ion transitions of m/z 107 --> 90, m/z 107 --> 62 and m/z 90 --> 62 for EC, as well as m/z 112 --> 63 for the LEC internal standard. The limits of detection and quantification were 0.6 and 1.2 microg kg(-1), respectively, and the recovery of the method was 101 +/- 10% at 10 microg kg(-1) and 98 +/- 5% at 100 microg kg(-1). The precision of the method, established under conditions of intermediate reproducibility, did not exceed a relative standard deviation of 7%. The quantitative performance of the new GC/PICI-SRM procedure compared favourably with that of a reference method based on GC/MS and selected ion monitoring (correlation coefficient, r = 0.997). However, the new method had the advantages of reduced sample preparation time, improved sensitivity and unambiguous identification of EC at all concentrations. Application of the new method to the analysis of 50 UK breads showed that levels of EC ranged from 0.6 to 2.3 microg kg(-1) in retail products and from 3.1 to 12.2 microg kg(-1) for breads prepared using domestic breadmaking machines (dry weight basis). Toasting bread in a domestic toaster led to increases of between two- and three-fold in mean EC concentrations.     

A new high-performance liquid chromatographic/electrospray ionization tandem mass spectrometric method for the simultaneous determination of cyclophosphamide, methotrexate and 5-fluorouracil as markers of surface contamination for occupational exposure monitoring

A new high-performance liquid chromatographic/electrospray ionization tandem mass spectrometric (HPLC/ESI-MS/MS) method was developed for the simultaneous quantification of 5-fluorouracil (5FU), methotrexate (MTX) and cyclophosphamide (CP) in environmental samples. These compounds, commonly used in the treatment of cancer, are recognized as genotoxic. In order to estimate the occupational exposure of hospital personnel handling these drugs, wipe samples were taken from the working surfaces and directly analyzed (with trophosphamide as internal standard) using a reversed-phase capillary column and MS/MS detection. This is the first HPLC/MS/MS method for the simultaneous determination of 5FU, MTX and CP. The present method offers high sensitivity, with detection limits of 1.1 microg l(-1) for MTX and CP and 33.3 microg l(-1) for 5FU, avoiding any sample preconcentration procedure. Rapidity, specificity, high accuracy (mean values between 92.4 and 99.9%) and precision (mean RSD values between 3.4 and 12.1%) make the method suitable for the routine determination of these three antineoplastic drugs.     

Development and validation of an HPLC method for the determination of penicillin antibiotics residues in bovine muscle according to the European Union Decision 2002/657/EC

A high-performance liquid chromatographic method was developed for the determination of five penicillins: penicillin G (PENG), penicillin V (PENV), oxacillin (OX), cloxacillin (CLO), and dicloxacillin (DICLO), in bovine muscle. Samples were macerated with a mixture of H(2)O/CH(3)CN (1:1) and purified using RP-8 Adsorbex SPE cartridges after centrifugation, with mean recovery from spiked samples higher than 89%. The separation of the examined penicillins was achieved on an analytical column, an Inertsil C8 5 microm, 250x4 mm(2), at ambient temperature. The mobile phase consisted of 0.1% TFA/ACN 50:50 v/v delivered isocratically at a flow rate of 1.1 mL/min. Analytes were monitored at 240 nm. The procedure was validated according to the European Union Decision 2002/657/EC by means of selectivity, stability, decision limit, detection capability, accuracy, and precision. Method's LOQ values achieved were 54 microg/kg for PENG and DICLO, 46 microg/kg for PENV, 16 microg/kg for OX, and 43 microg/kg for DICLO. The detection capabilities (CC(beta)) were 73.6 microg/kg for PENG, 29.1 microg/kg for PENV, 350.6 microg/kg for OX, 379.9 microg/kg for CLO, and 355.8 microg/kg for DICLO. The method was applied to various samples from the local market. Two penicillins were identified by photodiode array (PDA) detection and quantified.     

Validation of chiral capillary electrophoresis-electrospray ionization-mass spectrometry methods for ecstasy and methadone in plasma

Due to its selectivity and sensitivity, CE coupled to MS (CE-MS) has evolved as a useful analytical tool for determining drugs and metabolites in biological samples. A generic CE-ESI/MS method was developed for the enantioselective determination of basic compounds in plasma. The use of protein precipitation (PP) prior to a hydrodynamic injection (HD) was well adapted to high-concentration samples (>1 ppm) and allowed high throughput. In contrast, the combination of liquid-liquid extraction (LLE) and electrokinetic injection (EK) was time-consuming but did allow detection at the ppb level. Both approaches were fully validated according to ICH guidelines and SFSTP protocols for two pharmaceutical compounds (ecstasy and methadone (MTD)). Deuterated internal standards (IS) in the analytical procedures were used and good quantitative performance was obtained in terms of trueness and precision (repeatability and intermediate precision) since accuracy profiles were within the acceptance limits (30% for biological assay). Methods were linear over the concentration range of 0.50-175 ng/mL and 0.25-5 microg/mL for LLE-EK and PP-HD procedures, respectively. The LLE-EK methodology was finally successfully applied to quantitation of ecstasy and MTD in real cases obtained from toxicology.     

Determination of lincomycin and tylosin residues in honey by liquid chromatography/tandem mass spectrometry

A simple and rapid analytical method was developed for the determination of lincomycin and tylosin residues in honey as part of field studies examining the efficacy and target animal safety of these antibiotics to control American foulbrood disease in honey bees. Residues of the antibiotics were determined using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). Honey samples were diluted and injected directly into the LC/MS/MS system without additional cleanup by solid-phase extraction or liquid-liquid partitioning. A six-port valve system was utilized to selectively route eluant from the LC column into the mass spectrometer only during a relatively short portion of the chromatographic run corresponding to the elution of the analytes of interest. Minimal contamination of the MS source chamber was observed despite the analysis of large numbers of samples. Using internal standard quantitation, excellent accuracy and precision were obtained with no apparent matrix-to-matrix variation. Based on the analysis of fortified replicates, the mean percent deviation from the theoretical concentration and the percent relative standard deviation were both less than 10% for tylosin over an analytical range of 10-1000 microg/kg. Slightly higher mean percent deviations and relative standard deviations were observed for the analysis of lincomycin in fortified replicate samples. The method detection limits were determined to be 5 and 2 microg/kg for lincomycin and tylosin, respectively.     

Analytical procedure to simultaneously measure trace amounts of trenbolone acetate and beta-trenbolone residues in porcine muscle using HPLC-UVD and MS

The current study was undertaken to validate the performance for the determination of both TBA and beta-trenbolone (beta-TB) residues in porcine muscle at concentrations required to monitor compliance with the maximum residue limit (MRL). The method involves a one phase liquid-liquid extraction, cleanup with low-temperature fat precipitation, separation of the respective compounds by HPLC on a Capcell pak C(18) column, use of a methanol-water isocratic system as an eluent, and measurement by UV absorbance detection at 340 nm. Both compounds were confirmed using LC-MS/MS with electrospray interface (ESI) and a triple quadrupole (QqQ) analyzer. The method was found to be precise and accurate, with a linearity range of 1-10 microg/kg (r(2) >0.973). The intra- and interday precision showed good reproducibility with RSDs < or =13.25%. The LODs were 0.12 and 0.22 microg/kg, and the LOQs were 0.37 and 0.66 microg/kg, for TBA and beta-TB, respectively. The applicability of the method was demonstrated by analyzing real samples collected from major cities in the Republic of Korea. No residues of the selected compounds were detected in any of the samples. The advantages of our method are that it is: selective, sensitive, requires a short time for analysis (13 min), and performs simple sample extraction and clean-up procedure with low-temperature fat precipitation as compared to the previously published methods.     

Validation of a gas chromatography/triple quadrupole mass spectrometry based method for the quantification of pesticides in food commodities

A new multiresidue method has been validated in cucumber matrix for the routine analysis of 130 multiclass pesticide residues by gas chromatography/triple quadrupole mass spectrometry. The pesticides were extracted with ethyl acetate. A first identification of the pesticides was based on a tandem mass spectrometric (MS/MS) screening method, which monitors a single transition for each target compound, in less than 12 min. After that, potentially non-negative samples were analyzed again by the MS/MS confirmation/quantification method, which monitors two or three MS/MS transitions for each compound, also in less than 12 min. Performance characteristics, such as trueness, precision, linear range, detection limit (LOD) and quantification limit (LOQ), for each pesticide were calculated. The average recoveries obtained ranged between 70 and 120% at three different fortification levels (25, 200 and 500 microg/kg) with precision, expressed as relative standard deviation (RSD), values lower than 15%. The calculated LOD and LOQ were typically <3.2 and 9.6 microg/kg, respectively. Such limits were much lower than the maximum residue levels (MRLs) established by European legislation. The proposed methodology was applied to the determination of pesticides in real vegetable samples from Almería (Spain).     

Development and evaluation of a candidate reference measurement procedure for the determination of testosterone in human serum using isotope dilution liquid chromatography/tandem mass spectrometry

A candidate reference measurement procedure for total testosterone in human serum involving isotope dilution (ID) coupled with liquid chromatography/tandem mass spectrometry (LC/MS/MS) has been developed and critically evaluated. The endogenous testosterone and its internal standard (testosterone-d ₃) were extracted from the serum matrix using a combination of solid-phase extraction and liquid–liquid extraction prior to reversed-phase LC/MS/MS. Accuracy of the measurements was evaluated by a recovery study using testosterone-spiked serum. The recovery of the added testosterone ranged from 100.0 to 100.3%. This method was applied to the determination of testosterone in frozen serum samples from three individual donors (one female and two males) with the testosterone concentrations ranging from 0.3 to 8.5 ng g⁻¹. Repeatability with within-set coefficients of variation (CVs) from 0.1 to 1.0% and intermediate precision with between-set CVs from 0.1 to 0.5% for both female and male serum materials were demonstrated. Excellent linearity was obtained for all linear regression lines. The detection limit at a signal-to-noise ratio of approximately 3 was 2 pg of testosterone in serum. Structural analogs as well as testosterone metabolites were tested and found to not interfere with the measurement of testosterone. This well-characterized LC/MS/MS method for serum testosterone, which demonstrates good accuracy and precision, and low susceptibility to interferences, qualifies as a reference measurement procedure that can be used to provide an accuracy base to which routine methods for testosterone can be compared and that will serve as a standard of higher order for measurement traceability.     

Development and in-house validation of a liquid chromatography-electrospray-tandem mass spectrometry method for the simultaneous determination of Sudan I, Sudan II, Sudan III and Sudan IV in hot chilli products

An accurate method based on the use of reversed-phase (RP) liquid chromatography-tandem mass spectrometry interfaced with electrospray (LC-ESI-MS/MS) was devised for the determination of Sudan I, Sudan II, Sudan III and Sudan IV in hot chilli food samples. A simple sample treatment procedure entailing the use of an extraction step with acetone without clean-up was developed. A C18 column with an aqueous formic acid/methanol mixture as the mobile phase was used under isocratic conditions. Mass spectral acquisition was done in positive ion mode by applying selected reaction monitoring of three fragmentation transitions per compound to provide a high degree of selectivity. The method was in-house validated in terms of detection limits (LOD), quantitation limits (LOQ), linearity, sensitivity, accuracy, recovery, and selectivity on two kinds of hot chilli sauces. Good results in the low ng/g level were obtained for LOD and LOQ of all analytes in matrices. Under both intra-day repeatability (R.S.D. between 1 and 13%) and intermediate precision (about 5-15% R.S.D. for both chilli sauce matrices) conditions, precision proved to be typical of determinations based on electrospray LC-MS and acceptable for routine monitoring purposes. Extraction recoveries for all four azo-dyes in chilli tomato sauce ranged from 92 to 103% at a spiking level of 5 microg/kg, whereas values between 72 and 97% were calculated in chilli tomato and cheese sauce at the same concentration level. The applicability of the method to the determination of Sudan azo-dyes in hot chilli products was demonstrated.     

High-throughput determination of carbocysteine in human plasma by liquid chromatography/tandem mass spectrometry: application to a bioequivalence study of two formulations in healthy volunteers

A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method to determine carbocysteine in human plasma was developed and fully validated. After methanol-induced protein precipitation of the plasma samples, carbocysteine was subjected to LC/MS/MS analysis using electrospray ionization (ESI). The MS system was operated in the selected ion monitoring (SRM) mode. Chromatographic separation was performed on a Hypurity C18 column (i.d. 2.1 mm x 50 mm, particle size 5 microm). The method had a chromatographic running time of 2.0 min and linear calibration curves over the concentration ranges of 0.1-20 microg/mL for carbocysteine. The lower limit of quantification (LLOQ) of the method was 0.1 microg/mL for carbocysteine. The intra- and inter-day precision was less than 7% for all quality control samples at concentrations of 0.5, 2.0, and 10.0 microg/mL. These results indicate that the method was efficient with a simple preparation procedure and a very short running time (2.0 min) for carbocysteine compared with methods reported in the literature and had high selectivity, acceptable accuracy, precision and sensitivity. The validated LC/MS/MS method has been successfully used to a bioequivalence study of two tablet formulations of carbocysteine in healthy volunteers.     

Comparison of the effectiveness of recent extraction procedures for antibiotic residues in bovine muscle tissues

Acetonitrile extraction followed by primary-secondary amine dispersive SPE cleanup QuEChERS (quick, easy, cheap, effective, rugged, and safe), was compared to pressurized liquid extraction (PLE) using water at 70 degrees C for 10 min at 1500 psi for the determination of 16 veterinary drugs in bovine muscle tissues by LC/MS/MS. PLE was significantly more effective for the extraction of veterinary drugs (ranging from 69 to 103% with RSD < or = 18%) than QuEChERS (ranging from 19 to 89% with RSD < or = 19%). Linearity of the calibration curves was obtained over the range considered from 10 microg/kg or LOQ to 1000, microg/kg) with r2 > or = 0.99 for all the analytes by both methods. Although an internal standard was used, matrix effects were corrected using matrix- matched standards. LODs were from 5 to 30 microg/kg for PLE and from 10 to 100 microg/kg for QuEChERS. To establish and assess the most efficient conditions for each extraction method, statistical parametric and nonparametric tests were used. PLE with water almost eliminates the use or generation of hazardous wastes. The two methods were applied successfully in a routine analysis during surveys in 2008.