Simultaneous pharmacokinetic and pharmacodynamic analysis of 5α-reductase inhibitors and androgens by liquid chromatography tandem mass spectrometry

AbstractBenign prostatic hyperplasia and prostate cancer can be treated with the 5α-reductase inhibitors, finasteride and dutasteride, when pharmacodynamic biomarkers are useful in assessing response. A novel method was developed to measure the substrates and products of 5α-reductases (testosterone, 5α-dihydrotestosterone (DHT), androstenedione) and finasteride and dutasteride simultaneously by liquid chromatography tandem mass spectrometry, using an ABSciex QTRAP® 5500, with a Waters Acquity™ UPLC. Analytes were extracted from serum (500µL) via solid-phase extraction (Oasis® HLB), with 13C3-labelled androgens and d9-finasteride included as internal standards. Analytes were separated on a Kinetex C18 column (150×3mm, 2.6µm), using a gradient run of 19min. Temporal resolution of analytes from naturally occurring isomers and mass +2 isotopomers was ensured. Protonated molecular ions were detected in atmospheric pressure chemical ionisation mode and source conditions optimised for DHT, the least abundant analyte. Multiple reaction monitoring was performed as follows: testosterone (m/z 289→97), DHT (m/z 291→255), androstenedione (m/z 287→97), dutasteride (m/z 529→461), finasteride (m/z 373→317). Validation parameters (intra- and inter-assay precision and accuracy, linearity, limits of quantitation) were within acceptable ranges and biological extracts were stable for 28 days. Finally the method was employed in men treated with finasteride or dutasteride; levels of DHT were lowered by both drugs and furthermore the substrate concentrations increased

Pros and cons of different therapeutic antibody formats for recombinant antivenom development.

Antibody technologies are being increasingly applied in the field of toxinology. Fuelled by the many advances in immunology, synthetic biology, and antibody research, different approaches and antibody formats are being investigated for the ability to neutralize animal toxins. These different molecular formats each have their own therapeutic characteristics. In this review, we provide an overview of the advances made in the development of toxin-targeting antibodies, and discuss the benefits and drawbacks of different antibody formats in relation to their ability to neutralize toxins, pharmacokinetic features, propensity to cause adverse reactions, formulation, and expression for research and development (R&D) purposes and large-scale manufacturing. A research trend seems to be emerging towards the use of human antibody formats as well as camelid heavy-domain antibody fragments due to their compatibility with the human immune system, beneficial therapeutic properties, and the ability to manufacture these molecules cost-effectively

MWNT reinforced melamine-formaldehyde containing alpha-cellulose

Multi-wall carbon nanotubes (MWNT) were used as reinforcement for melamine-formaldehyde (MF). They were oxidised in HNO3/ H2SO4 mixture and analyzed by means of X-ray Photoelectron Spectroscopy (XPS). Two anionic surfactants: sodium dodecyl sulphate (SDS) and sodium dodecylbenzenesulfonate (NaDDBS) were used to assist the dispersion of nanotubes. The MWNT content was varied from 0 to 1.0 wt%, and the influence of nanotubes on viscosity (flow curves) was measured. The viscosity of SDS-assisted aqueous solution of MF containing a small amount (0.1 wt%) of MWNT is low, and thus promising towards manufacturing processes. A film stacking-like manufacturing route was adapted to prepare ternary MWNT/cellulose/MF thin composite layers. Transmission electron microscopy (TEM) and Light microscopy (LM) were used to observe dispersion. The addition of 0.1 wt% MWNT assisted with SDS increased the storage modulus and tensile strength by 50%. Conventional calculations of the Young's modulus were made. Values underestimating the modulus were found. The observed discrepancy was attributed to polymer chain immobilisation as a result of crosslinking