Optimised extraction of heterocyclic aromatic amines from blood using hollow fibre membrane liquid-phase microextraction and triple quadrupole mass spectrometry

Heterocyclic aromatic amines (HCA) are carcinogenic mutagens formed during cooking of proteinaceous foods, particularly meat. To assist in the ongoing search for biomarkers of HCA exposure in blood, a method is described for the extraction from human plasma of the most abundant HCAs: 2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) (and its isomer 7,8-DiMeIQx), using Hollow Fibre Membrane Liquid-Phase Microextraction. This technique employs 2.5 cm lengths of porous polypropylene fibres impregnated with organic solvent to facilitate simultaneous extraction from an alkaline aqueous sample into a low volume acidic acceptor phase. This low cost protocol is extensively optimised for fibre length, extraction time, sample pH and volume. Detection is by UPLC-MS/MS using positive mode electrospray ionisation with a 3.4 min runtime, with optimum peak shape, sensitivity and baseline separation being achieved at pH 9.5. To our knowledge this is the first description of HCA chromatography under alkaline conditions. Application of fixed ion ratio tolerances for confirmation of analyte identity is discussed. Assay precision is between 4.5 and 8.8% while lower limits of detection between 2 and 5 pg/mL are below the concentrations postulated for acid-labile HCA-protein adducts in blood.

Is the raised volume rapid thoracic compression technique ready for use in clinical trials in infants with cystic fibrosis?

The European Cystic Fibrosis Society Clinical Trial Network (ECFS-CTN) has established a Standardization Committee to undertake a rigorous evaluation of promising outcome measures with regard to use in multicentre clinical trials in cystic fibrosis (CF). The aim of this article is to present a review of literature on clinimetric properties of the infant raised-volume rapid thoracic compression (RVRTC) technique in the context of CF, to summarise the consensus amongst the group on feasibility and answer key questions regarding the promotion of this technique to surrogate endpoint status.

METHODS: A literature search (from 1985 onwards) identified 20 papers that met inclusion criteria of RVRTC use in infants with CF. Data were extracted and tabulated regarding repeatability, validity, correlation with other outcome measures, responsiveness and reference values. A working group discussed the tables and answered 4 key questions.

RESULTS: Overall, RVRTC in particular forced expiratory volume in 0.5s, showed good clinimetric properties despite presence of individual variability. Few studies showed a relationship between RVRTC and inflammation and infection, and to date, data remains limited regarding the responsiveness of RVRTC after an intervention. Concerns were raised regarding feasibility in multi-centre studies and availability of reference values.

CONCLUSION: The ECFS-CTN Working Group considers that RVRTC cannot be used as a primary outcome in clinical trials in infants with CF before universal standardization of this measurement is achieved and implementation of inter-institutional networking is in place. We advise its use currently in phase I/II trials and as a secondary endpoint in phase III studies. We emphasise the need for (1) more short-term variability and longitudinal 'natural history' studies, and (2) robust reference values for commercially available devices.

Rotary moulding of ceramic hollow wares

A novel processing method for the fast and economic production of hollow ceramic components has been developed by combining in situ coagulation moulding with a modified version of the technique of rotary moulding[Binner, J. G. P., Al-Dawery, I. A., Tari, G. and Yan, Y., Rotary casting technique. UK Patent application No. 0506349.0, March 2005], the latter being adapted from the polymer industry. The process was found to require a high solids content suspension, hence development work was performed in this direction though in the end a new, commercial suspension was utilised. Of the three forming routes of gel casting, direct coagulation casting and in situ coagulation moulding, the latter was found to be the most promising for the new process of rotary moulding of ceramics. Due to the low value of clay-based ceramics, a new low cost coagulant was identified and the effect of lactone concentration and temperature on setting time determined. Following substantial optimisation work, it was found that a two-speed approach to multi-axial rotation was the most successful; medium sized cream jugs could be produced in just 7 min. With respect to mould materials, the porous resin normally used for pressure casting of sanitary ware was found to be the best option, though since this is quite expensive conventional plaster-of-paris moulds were found to be a suitable material to enable companies, particularly SMEs, to become familiar with the technology whilst avoiding high costs for trials. The processed articles could be successfully fired and glazed using gas-fired kilns with no sign of any black cores. Major advantages of the process include the ability to precisely calculate the amount of ceramic slip required, eliminating either slip wastage or the need to pour used slip back into the virgin material as currently happens with slip casting. In addition, since the precursor suspension has a very high solids content, the time and energy required to dry the green product and associated moulds has been considerably reduced. © 2008 Elsevier Ltd. All rights reserved.