A green and effective method for the determination of metalaxyl enantiomers in tobacco and soil by supercritical fluid chromatography-tandem mass spectrometry.

We reported a new methodology for the stereoselective determination of metalaxyl enantiomers in tobacco and soil. The QuEChERS (quick, easy, cheap, effective, rugged, and safe) method was used for the extraction and clean-up of the tobacco and soil samples. Separation of the metalaxyl enantiomers was performed on an ACQUITY UPC2 Trefoil CEL1 chiral column coupled with supercritical fluid chromatography with tandem mass spectrometry (SFC-MS/MS), and the run time was only 5 minutes. Under the optimized conditions, the recoveries for the enantiomers were between 78.2% and 93.3% with intraday relative standard deviations (RSDs) ranging from 1.1% to 5.4%. The limit of detection (LOD) for the enantiomers in tobacco and soil varied from 0.005 to 0.007 mg/kg, and the limit of quantitation (LOQ) ranged from 0.017 to 0.020 mg/kg. In this method, only a small amount of methanol was consumed to obtain a rapid stereoselective separation. This proposed method showed good accuracy and precision and might be suitable for fast enantioselective determination of metalaxyl in food and environmental samples. The developed method was further validated by application to the analysis of authentic samples.

[Advances in the research of pharmacogenomics of tamoxifen].

Tamoxifen (TAM) is the most common nonsteroidal antiestrogen agent, which has been widely used in the prevention of recurrence of estrogen or progesterone receptor-positive breast cancer in patients. It is metabolized by cytochrome P450 oxidases to its active metabolite (4-hydroxytamoxifen, 4-OH-TAM) and endoxifen (EDF), which played a critical role in the therapy. 4-OH-TAM and EDF have 30- to 100-fold more potency than TAM in the suppression of estrogen-dependent breast cancer cell proliferation. CYP3A4 and CYP2D6, as the key drug-metabolizing enzymes in those metabolic actions, are known to have several alleles. Genetic polymorphisms of CYP2D6 and CYP3A4 will influence the plasma concentrations of active TAM metabolites and clinical outcomes for breast cancer patients treated with TAM. The genetic polymorphisms of drug transporters, involved in the disposition of active TAM metabolites, also have the potential to influence the plasma concentrations of active TAM metabolites and clinical outcome for the treatment of breast cancer. In this review, we summarized the association of the genetic polymorphisms in the metabolic enzymes and transporters involved in the metabolism and disposition of TAM with the metabolite concentration, efficacy and adverse effects of TAM, which provides a fundamental reference for further pharmacogenomic study and clinical use of TAM.

Determination of Commonly Used Multiclass Pesticide Residues in Tobacco and Cigarette Smoke by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry.

A novel method has been developed for the simultaneous determination of multiclass pesticide residues in tobacco and cigarette smoke, using a modified QuEChERS (quick, easy, cheap, effective, rugged and safe) procedure and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Cigarette mainstream smoke particulate was collected on a Cambridge filter pad. Pesticide residues was extracted with an aqueous solution, back extracted into acetonitrile after freezing, purified by dispersive solid phase extraction with primary-secondary amine adsorbents and analyzed by UPLC-MS/MS. The obtained mean recoveries of 16 pesticides commonly used on tobacco at three fortification levels (5.9, 94.1 and 352.9 ng g-1) ranged from 69.3 to 115.9% with relative standard deviations between 2.4 and 11.3%. The limits of detection ranged from 0.14 to 13.28 ng g-1. Finally, the proposed method was applied to study the pesticide smoke transfer ratio in 2 cigarettes with pesticide standard spiked and 51 cigarettes with one or more pesticide residues. The transfer ratio of pesticides residue in tobacco into the smoke might be much less than that from artificially spiked tobacco (<25%) with spiking levels varied from 1.88 to 9.41 µg g-1. The transfer ratio of pesticide from artificially spiked tobacco into cigarette mainstream smoke was from 0.0 to 56.5%, and pesticide residues from tobacco into cigarette smoke were from 0.0 to 26.1% using the ISO smoking method (ISO 3308 2012).

Quantitation of Apremilast in Beagle Dogs Plasma by UPLC-MS-MS and Its Application to Pharmacokinetic Studies.

A sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method for the determination of apremilast in beagle dog plasma has been developed and successfully validated in the current study. Clopidogrel was employed as an internal standard (IS), and liquid-liquid extraction by tert-butylmethyl ether was used for sample preparation. Chromatographic separation was achieved on a UPLC BEH Shield RP18 column (50 mm × 2.1 mm, 1.7 µm) with 5 mM ammonium formate water and 5 mM ammonium formate methanol as the mobile phase with gradient elution. Calibration plots were linear in the range of 2-3000 ng/mL for apremilast in beagle dog plasma. Mean recoveries of apremilast in beagle dogs plasma ranged from 87.4% to 97.4%. The intrarun and interrun precision was less than 6% and 9%, respectively, with the accuracy between 92.4% and 101.1%. The method has also been successfully applied in the pharmacokinetics study of apremilast. The mean t1/2Z was 5.41 h for 30 mg·day-1 for beagle dogs after oral administration. The AUC0-t increased linearly from 3.51 to 1802.13 µg L-1 ∗h after administration of single doses.

Separation and quantitation of three acidic herbicide residues in tobacco and soil by dispersive solid-phase extraction and UPLC-MS/MS.

A method for the determination of three acidic herbicides, dicamba, 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) in tobacco and soil has been developed based on the use of liquid-liquid extraction and dispersive solid-phase extraction (dispersive-SPE) followed by UPLC-MS/MS. Two percentage of (v/v) formic acid in acetonitrile as the extraction helped partitioning of analytes into the acetonitrile phase. The extract was then cleaned up by dispersive-SPE using primary secondary amine as selective sorbents. Quantitative analysis was done in the multiple-reaction monitoring mode using stable isotope-labeled internal standards for each compound. A separate internal standard for each analyte is required to minimize sample matrix effects on each analyte, which can lead to poor analyte recoveries and decreases in method accuracy and precision. The total analysis time was <4 min. The linear range of the method was from 1 to 100 ng mL(-1) with a limit of detection of each herbicide varied from 0.012 to 0.126 ng g(-1). The proposed method is faster, more sensitive and selective than the traditional methods and more accurate and robust than the published LC-MS/MS methods.