Rapid and sensitive determination of acetylsalicylic acid and salicylic acid in plasma using liquid chromatography–tandem mass spectrometry: application to pharmacokinetic study

A simple and sensitive analytical method using liquid chromatography–tandem mass spectrometry (LC/MS/MS) for determination of acetylsalicylic acid (aspirin, ASA) and its major metabolite, salicylic acid (SA), in animal plasma has been developed and validated. Both ASA and SA in plasma samples containing potassium fluoride were extracted using acetonitrile (protein precipitation) with 0.1% formic acid in it. 6‐Methoxysalicylic acid was used as the internal standard (IS). The compounds were separated on a reversed‐phase column. The multiple reaction monitoring mode was used with ion transitions of m/z 178.9 → 136.8, 137.0 → 93.0 and 167.0 → 123.0 for ASA, SA and IS, respectively. The lower limits of quantification for ASA and SA were 3 and 30 ng/mL, respectively. The developed method was successfully applied for the evaluation of pharmacokinetics of ASA and SA after p.o. and i.v. administration of 1 mg/kg to rats. Copyright © 2009 John Wiley & Sons, Ltd.     

Iridium catalyzed alkylation of 2′-hydroxyacetophenone with alcohols under thermal or microwave conditions

2′-Hydroxyacetophenone was alkylated with a range of substituted benzyl and heteroaryl alcohols to afford the corresponding C-alkylated products in good yields under microwave irradiation. The C-alkylated products were reacted with bromoacetonitrile to afford 2-amino-3-benzyl 1,4-naphthoquinone derivatives in moderate yields.     

Utilizing inverse micelles to synthesize calcium phosphate nanoparticles as nano-carriers

The aim of this study was to investigate the feasibility of the inverse micelles (IM) technique in producing protein-loaded calcium phosphate nanoparticles (CaP NPs), and to compare this technique with the conventional co-precipitation (co-ppt) technique. In this study, bovine serum albumin and lysozyme were used as model proteins. The results show that CaP NPs produced by IM were shown to be spherical and homogenous in size of ~50 nm. Protein loading efficiency of the IM technique was shown to be much higher than CaP NPs synthesized through co-ppt technique. X-ray photoelectron spectroscopy shows that proteins were not adsorbed onto the surface of IM-synthesized CaP NPs, which suggested that the proteins were entrapped within the particle matrix. Release studies show that protein release was more rapid at lower pH conditions (pH 5 and 6) than at physiological pH of 7.4. A burst release was observed for co-ppt CaP NPs, while a continuous release of protein was observed for IM-produced CaP NPs. This study shows the superiority of the IM technique in preparing pH responsive CaP NPs as nano-carriers.     

Cooperative Lewis Pairs Based on Late Transition Metals: Activation of Small Molecules by Platinum(0) and B(C6F5)3

A Lewis basic platinum(0)–CO complex supported by a diphosphine ligand and B(C₆F₅)₃ act cooperatively, in a manner reminiscent of a frustrated Lewis pair, to activate small molecules such as hydrogen, CO₂, and ethene. This cooperative Lewis pair facilitates the coupling of CO and ethene in a new way.     

Quantitative Proteomic Analysis of Optimal Cutting Temperature (OCT) Embedded Core-Needle Biopsy of Lung Cancer

With recent advances in understanding the genomic underpinnings and oncogenic drivers of pathogenesis in different subtypes, it is increasingly clear that proper pretreatment diagnostics are essential for the choice of appropriate treatment options for non-small cell lung cancer (NSCLC). Tumor tissue preservation in optimal cutting temperature (OCT) compound is commonly used in the surgical suite. However, proteins recovered from OCT-embedded specimens pose a challenge for LC-MS/MS experiments, due to the large amounts of polymers present in OCT. Here we present a simple workflow for whole proteome analysis of OCT-embedded NSCLC tissue samples, which involves a simple trichloroacetic acid precipitation step. Comparisons of protein recovery between frozen versus OCT-embedded tissue showed excellent consistency with more than 9200 proteins identified. Using an isobaric labeling strategy, we quantified more than 5400 proteins in tumor versus normal OCT-embedded core needle biopsy samples. Gene ontology analysis indicated that a number of proliferative as well as squamous cell carcinoma (SqCC) marker proteins were overexpressed in the tumor, consistent with the patient’s pathology based diagnosis of “poorly differentiated SqCC”. Among the most downregulated proteins in the tumor sample, we noted a number of proteins with potential immunomodulatory functions. Finally, interrogation of the aberrantly expressed proteins using a candidate approach and cross-referencing with publicly available databases led to the identification of potential druggable targets in DNA replication and DNA damage repair pathways. We conclude that our approach allows LC-MS/MS proteomic analyses on OCT-embedded lung cancer specimens, opening the way to bring powerful proteomics into the clinic.

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Cyclization of protected N-acylhydroxyguanidine to 3-amino-1,2,4-oxadiazole

The acid mediated cyclization of a protected N-acylhydroxyguanidine into the corresponding 3-amino-1,2,4-oxadiazole and confirmation of its structure by single crystal X-ray crystallography is reported herein. The yield of the cyclization is comparable to literature reports utilizing alternative procedures. Importantly, these new conditions provide complementary chemoselectivity to current synthetic procedures which may be useful for the synthesis of 3-amino-1,2,4-oxadiazoles in general.