The preclinical pharmacology of the high affinity anti-IL-6R Nanobody® ALX-0061 supports its clinical development in rheumatoid arthritis.

Introduction: The pleiotropic cytokine interleukin-6 (IL-6) plays an important role in the pathogenesis of different diseases, including rheumatoid arthritis (RA). ALX-0061 is a bispecific Nanobody® with a high affinity and potency for IL-6 receptor (IL-6R), combined with an extended half-life by targeting human serum albumin. We describe here the relevant aspects of its in vitro and in vivo pharmacology.

LC-MS/MS quantification of next-generation biotherapeutics: a case study for an IgE binding Nanobody in cynomolgus monkey plasma.

Background: Nanobodies(®) are therapeutic proteins derived from the smallest functional fragments of heavy chain-only antibodies. The development and validation of an LC-MS/MS-based method for the quantification of an IgE binding Nanobody in cynomolgus monkey plasma is presented.

Results: Nanobody quantification was performed making use of a proteotypic tryptic peptide chromatographically enriched prior to LC-MS/MS analysis.

Multi-residue liquid chromatography/tandem mass spectrometric analysis of beta-agonists in urine using molecular imprinted polymers.

Ion suppression, a matrix effect that affects quantitative mass spectrometry, is one of the main problems encountered in liquid chromatography/tandem mass spectrometry. Two different clean-up steps for the multi-residue analysis of beta-agonists in urine were evaluated with respect to minimisation of ion suppression, namely, a mixed-phase solid phase extraction (SPE) column, i.e.

Development and validation of an analytical method for detection of estrogens in water.

An analytical procedure enabling routine analysis of four environmental estrogens at concentrations below 1 ng L(-1) in estuarine water samples has been developed and validated. The method includes extraction of water samples using solid-phase extraction discs and detection by gas chromatography (GC) with tandem mass spectrometry (MS-MS) in electron-impact (EI) mode. The targeted estrogens included 17alpha- and 17beta-estradiol (aE2, bE2), estrone (E1), and 17alpha-ethinylestradiol (EE2), all known environmental endocrine disruptors.

Multi-residue liquid chromatography/tandem mass spectrometry method for the detection of non-steroidal anti-inflammatory drugs in bovine muscle: optimisation of ion trap parameters.

A multi-residue liquid chromatography/tandem mass spectrometry method (LC/MS2) was developed for the detection of the non-steroidal anti-inflammatory drugs acetylsalicylic acid (via the marker residue salicylic acid), flunixin, phenylbutazone, tolfenamic acid, meloxicam and ketoprofen, in bovine muscle. After extraction of the bovine muscle with acetonitrile, the cleanup was performed using a Oasis HLB column. The evaporated eluate was reconstituted and analysed by LC/MS2.

Testosterone and energy metabolism in the estuarine mysid Neomysis integer (Crustacea: Mysidacea) following exposure to endocrine disruptors.

A diverse set of reference compounds suspected of having an endocrine-disrupting mode of action (i.e., testosterone, flutamide, ethinylestradiol, precocene, nonylphenol, fenoxycarb, and methoprene) were tested for acute toxicity to the estuarine mysid Neomysis integer (Crustacea: Mysidacea).

Testosterone metabolism in the estuarine mysid Neomysis integer (Crustacea; Mysidacea) following tributyltin exposure.

Current evidence suggests that the biocide tributyltin (TBT) causes the development of imposex, a state of pseudohermaphrodism in which females exhibit functional secondary male characteristics, by altering the biotransformation or elimination of testosterone. Imposex in gastropods following TBT exposure is the most complete example of the effects of an endocrine disrupter on marine invertebrates. Previous studies have demonstrated that the estuarine mysid Neomysis integer converts testosterone into multiple polar and nonpolar metabolites resulting from both phase I and phase II biotransformations.