Phosphole formation by 1,1-carboboration--reactions of bis-alkynyl phosphanes with a frustrated P/B Lewis pair.

The arylbis(phenylethynyl)phosphanes 1a,b (aryl = mesityl, 2,4,6-triisopropylphenyl) react with the frustrated P/B Lewis pair (P/B FLP) mes2PCH2CH2B(C6F5)2 (4) to give mixtures of three products; the major products, the phosphole systems 2a,b, are formed by a sequence of 1,1-carboboration reactions. One of the minor compounds (6a,b) is formed by 1,1-carboboration followed by internal 1,2-FLP addition to the remaining C ≡ C triple bond. The other minor compound of the product mixture (5a,b) is obtained by 1,2-FLP addition to one alkynyl moiety of the starting material. The products 5a, 6b and a derivative of the phosphole 2a (formed by FLP reaction with a terminal alkyne) were characterized by X-ray diffraction. The reaction of the arylbis(pentynyl)phosphanes 1c,d with the FLP 4 selectively gave the respective -B(C6F5)2/-CH2CH2-Pmes2 substituted phospholes 2c,d which were isolated as orange solids in high yields. Rapid strongly temperature dependent equilibration between open and closed PB FLP isomers was detected for both systems by NMR spectroscopy.

Simple and rapid quantification of gadolinium in urine and blood plasma samples by means of total reflection X-ray fluorescence (TXRF).

A simple and rapid method to determine gadolinium (Gd) concentrations in urine and blood plasma samples by means of total reflection X-ray fluorescence (TXRF) was developed. With a limit of detection (LOD) of 100 µg L(-1) in urine and 80 µg L(-1) in blood plasma and a limit of quantification (LOQ) of 330 µg L(-1) in urine and 270 µg L(-1) in blood plasma, it allows analyzing urine samples taken from magnetic resonance imaging (MRI) patients during a period of up to 20 hours after the administration of Gd-based MRI contrast agents by means of TXRF. By parallel determination of the urinary creatinine concentration, it was possible to monitor the excretion kinetics of Gd from the patient's body. The Gd concentration in blood plasma samples, taken immediately after an MRI examination, could be determined after rapid and easy sample preparation by centrifugation. All measurements were validated with inductively coupled plasma mass spectrometry (ICP-MS). TXRF is considered to be an attractive alternative for fast and simple Gd analysis in human body fluids during daily routine in clinical laboratories.

Structure characterisation of urinary metabolites of the cannabimimetic JWH-018 using chemically synthesised reference material for the support of LC-MS/MS-based drug testing.

As recently reported, the synthetic cannabinoid JWH-018 is the subject of extensive phase I and II metabolic reactions in vivo. Since these studies were based on LC-MS/MS and/or GC-MS identification and characterisation of analytes, the explicit structural assignment of the metabolites was only of preliminary nature, if possible at all. Here, we report the chemical synthesis of five potential in vivo metabolites of JWH-018 derivatives featuring an alkylcarboxy (M1), a terminal alkylhydroxy (M2), a 5-indolehydroxy (M3), an N-dealkylated 5-indolehydroxy (M4) and a 2'-naphthylhydroxy (5) analogue, respectively, and their characterisation by nuclear magnetic resonance spectroscopy. The collision-induced dissociation (CID) patterns of the protonated compounds were studied by high-resolution/high-accuracy tandem mass spectrometry (MS( n )) applying an LTQ Orbitrap with direct infusion and electrospray ionisation of target analytes. An unusual dissociation behaviour including a reversible ion-molecule reaction between a naphthalene cation (m/z 127) and water in the gas phase of the MS was shown to be responsible for nominal neutral losses of 10 u in the course of the CID pathway. LC-MS/MS-supported comparison of synthesised reference standards with an authentic urine sample using an API 4000 QTrap mass spectrometer identified the synthetic JWH-018 analogues M1-M4 as true in vivo metabolites, presuming a chromatographic separation of potentially present regioisomeric analogues. Existing doping control methods were expanded and validated according to international guidelines in order to allow for the detection of the carboxy and the alkylhydroxy metabolites, respectively, as urinary markers for the illegal intake of the synthetic cannabinoid JWH-018. Both metabolites were quantified in authentic doping control urine samples that had been suspicious of JWH-018 abuse after routine screening procedures, and a stable isotope-labelled (13)C(8)-(15)N-carboxy metabolite was synthesised for future analytical applications.