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Blood vessels in the tumor periphery have high pericyte coverage and are resistant to vascular disrupting agents (VDAs). VDA treatment resistance leads to a viable peripheral tumor rim that contributes to treatment failure and disease recurrence. Here, we provide evidence to support a hypothesis that shifting the target of VDAs from tumor vessel endothelial cells to pericytes disrupts tumor peripheral vessels and the viable rim, circumventing VDA treatment resistance. Through chemical engineering, we developed Z-GP-DAVLBH (from the tubulin-binding VDA desacetylvinblastine monohydrazide [DAVLBH]) as a prodrug that can be selectively activated by fibroblast activation protein [alpha] (FAP[alpha]) in tumor pericytes. Z-GP-DAVLBH selectively destroys the cytoskeleton of FAP[alpha]-expressing tumor pericytes, disrupting blood vessels both within the core and around the periphery of tumors. As a result, Z-GP-DAVLBH treatment eradicated the otherwise VDA-resistant tumor rim and led to complete regression of tumors in multiple lines of xenografts without producing the drug-related toxicity that is associated with similar doses of DAVLBH. This study demonstrates that targeting tumor pericytes with an FAP[alpha]-activated VDA prodrug represents a potential vascular disruption strategy in overcoming tumor resistance to VDA treatments., Introduction Vascular disrupting agents (VDAs), mainly comprising tubulinbinding compounds, act primarily on tumor vascular endothelial cells (ECs) and alter the cellular tubulin cytoskeleton. Ultimately, VDAs selectively destroy the well-established tumor [...]

A fast, sensitive and specific high-performance liquid chromatography tandem mass spectrometry method was developed for simultaneous determination of metformin and rosiglitazone in human plasma. With phenformin as an internal standard, the analysis was carried out on a C18column (50 mm × 2.1 mm, 3.5 μm) using a mobile phase consisting of acetonitrile–10 mM ammonium acetate (20:80, v/v). The detection was performed by tandem mass spectrometry via electrospray ionization. Linear calibration curves were obtained in the concentration of 1.054–263.5 ng/mL for rosiglitazone and 4.040–5050 ng/mL for metformin. The method was applicable to clinical pharmacokinetic study of metformin and rosiglitazone in healthy volunteers following oral administration. [ABSTRACT FROM AUTHOR]

Background: Aflatoxin (AF) ingestion through contaminated foodstuffs causes at least 250 000 deaths every year from hepatocellular carcinoma in China and sub-Saharan Africa. Objective: The main objective of the study was to determine the aflatoxin levels of oils in South Gondar, Ethiopia, and oils purchased from retail markets in Guangzhou, China. Methods: We used a rapid, sensitive, and selective HPLC-tandem mass spectrometry (MS/MS) method for the determination of aflatoxins in edible oils from China and Ethiopia using immunoaffinity column cleaning. Results: The level of contamination for Ethiopian oils ranged between 0.07 and 145.59 µg/kg for total aflatoxins. Of the 27 edible oil samples from Guangzhou, China, the total concentration of aflatoxins (AFB1 + AFB2 + AFG1 + AFG2) ranged between 0.03 and 2.23 µg/kg. Conclusions: The study concluded that the peanut oils from Ethiopia were contaminated with aflatoxins higher than the allowable limit set by many countries while the oils from China were safe for human consumption. Highlights: We first describe an HPLC-MS/MS method for the determination of aflatoxins in 48 edible oil samples from China and Ethiopia using immunoaffinity column cleaning. This is the first preliminary study done on Ethiopian edible oils, giving policy-makers and future researchers baseline data. It is also used to assess the aflatoxin levels of the Chinese edible oils from Guangzhou. Therefore, conducting a comparative study points out the severity of the problem and helps to formulate a new national standard for policy-makers, making this study imperative. [ABSTRACT FROM AUTHOR]

A chiral separation method was developed for the analysis of methamphetamine (METH) and amphetamine (AM) in hair by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The samples were extracted using methanol by ultrasonication in a high-temperature water bath. The chromatographic separation was performed on a SUPELCO Astec CHIROIOTIC ® V2 column with the mobile phase of methanol-20 mmol/L ammonium acetate aqueous solution containing 0.1% (v/v) formic acid (99:1, v/v). All the compounds showed linear relationship in the range of 15-300 ng/mg ( r >0.99). The limits of detection (LODs) of METH and AM were 0.1 ng/mg and 0.15 ng/mg, respectively. The limits of quantification (LOQs) of METH and AM were 0.4 ng/mg and 0.5 ng/mg, respectively. The inter-day precisions were all ≤ 6.8%, and the intra-day precisions were all ≤ 11.4%. Fifty drug abuse samples were determined by this method. Up to 70% of the cases were determined as S -(+)-METH and S -(+)-AM, while 18% of the cases were S -(+)-METH, S -(+)-AM, R -(-)-METH and R -(-)-AM. The proposed method is rapid, simple, and provides technical support and a scientific basis for the chiral analysis in actual hair samples for forensic toxicant identification.

Background: Aflatoxin (AF) ingestion through contaminated foodstuffs causes at least 250000 deaths every year from hepatocellular carcinoma in China and sub-Saharan Africa. Objective: The main objective of the study was to determine the aflatoxin levels of oils in South Gondar, Ethiopia, and oils purchased from retail markets in Guangzhou, China. Methods: We used a rapid, sensitive, and selective HPLC-tandem mass spectrometry (MS/MS) method for the determination of aflatoxins in edible oils from China and Ethiopia using immunoaffinity column cleaning. Results: The level of contamination for Ethiopian oils ranged between 0.07 and 145.59 μg/kg for total aflatoxins. Of the 27 edible oil samples from Guangzhou, China, the total concentration of aflatoxins (AFB1 + AFB2 + AFG1 + AFG2) ranged between 0.03 and 2.23 μg/kg. Conclusions: The study concluded that the peanut oils from Ethiopia were contaminated with aflatoxins higher than the allowable limit set by many countries while the oils from China were safe for human consumption. Highlights: We first describe an HPLC-MS/MS method for the determination of aflatoxins in 48 edible oil samples from China and Ethiopia using immunoaffinity column cleaning. This is the first preliminary study done on Ethiopian edible oils, giving policy-makers and future researchers baseline data. It is also used to assess the aflatoxin levels of the Chinese edible oils from Guangzhou. Therefore, conducting a comparative study points out the severity of the problem and helps to formulate a new national standard for policy-makers, making this study imperative.

A fast, sensitive and specific high-performance liquid chromatography tandem mass spectrometry method was developed for simultaneous determination of metformin and rosiglitazone in human plasma. With phenformin as an internal standard, the analysis was carried out on a C(18) column (50 mm × 2.1 mm, 3.5 μm) using a mobile phase consisting of acetonitrile-10 mM ammonium acetate (20:80, v/v). The detection was performed by tandem mass spectrometry via electrospray ionization. Linear calibration curves were obtained in the concentration of 1.054-263.5 ng/mL for rosiglitazone and 4.040-5050 ng/mL for metformin. The method was applicable to clinical pharmacokinetic study of metformin and rosiglitazone in healthy volunteers following oral administration.

Objective: To establish a method for the determination of streptomycin in honey by determined hydrophilic interaction chromatography combined with tandem mass spectrometry (HILIC-MS/MS)., Methods: A hilic column was used, and the mobile phase was consisted of acetonitrile (5 mmol/L ammonium acetate and 0.1% formic acid, 60:40). Samples were extracted by the cation-exchange SPE cartridge. The extraction samples were then identified and quantitated by HILIC-ESI-MS/MS., Results: Linear calibration curves were obtained at the concentration ranges from 10. 5 microg/kg to 105 microg/kg (the correlation coefficients were above 0.99). The limit of detection was 1.05 microg/kg. The average recoveries for streptomycin spiked in honey ranged from 71.3 to 82.5% and their relative standard were between 3.4% and 8.2%., Conclusion: The method for determination of streptomycin in honey could be simple, sensitive and accurate.