Reflecting on Bioanalysis with the Senior Editors.

A previous Senior Editor, and the present Senior Editor of Bioanalysis reflect on their journeys in the field of bioanalysis, and with the journal. They discuss the evolution and progress of journal since its launch 10 years ago, and where they would like to see it heading in the future.

Conference report: the 19th International Reid Bioanalytical Forum.

The 19th International Reid Bioanalytical Forum was attended by over 120 participants. The Forum divided into approximately eight broad topics, although not always in the same session. The meeting commenced with a discussion on metabolites in safety testing, with emphasis on enabling technologies and philosophies. This was followed by a variety of regulatory-based issues initiated by Brian Booth of the US FDA. The next day started with a review of developing technologies in LC-MS and some anecdotal troubleshooting experiences. Interspersed among the sessions were experiences with bioanalysis in the discovery environment, biomarker-based topics and the rapidly developing field of the quantitation of proteins and peptides using LC-MS. The meeting finished with the best-attended session of the Forum on developing trends in using dried blood spots.

Conference report: Discussion on harmonization and globalization of bioanalytical guidances at the 19th International Reid Bioanalytical Forum.

The 19th International Reid Bioanalytical Forum was held in July 2011 in the UK. This open forum was an ideal meeting for extensive discussions on topics, such as global harmonization of bioanalytical guidance, in both formal and informal settings. Indeed, this meeting is well-known for its numerous networking opportunities during the 3-day conference and for an ethos of debate on practical solutions to problems encountered in bioanalytical science.

AMS method validation for quantitation in pharmacokinetic studies with concomitant extravascular and intravenous administration.

A technique has emerged in the past few years that has enabled a drug's intravenous pharmacokinetics to be readily obtained in humans without having to conduct extensive toxicology studies by this route of administration or expand protracted effort in formulation. The technique involves the intravenous administration of a low dose of (14)C-labelled drug (termed a tracer dose) concomitantly with a non-labelled extravascular dose given at therapeutically levels. Plasma samples collected over time are analysed to determine the total parent drug concentration by LC-MS (which essentially measures that arising from the oral dose) and by LC followed by accelerator mass spectrometry (AMS) to determine the (14)C-drug concentration (i.e., that arising from the intravenous dose). There are currently no published accounts of how the principles of bioanalytical validation might be applied to intravenous studies using AMS as an analytical technique. The authors describe the primary elements of AMS when used with LC separation and how this off-line technique differs from LC-MS. They then discuss how the principles of bioanalytical validation might be applied to determine selectivity, accuracy, precision and stability of methods involving LC followed by AMS analysis.

An AMS method to determine analyte recovery from pharmacokinetic studies with concomitant extravascular and intravenous administration.

The absolute bioavailability, clearance and volume of distribution of a drug can be investigated by administering a very low dose of the (14)C-drug intravenously along with a therapeutic nonlabeled dose by the extravascular route (typically orally). The total drug concentration is measured by an assay such as LC-MS and the (14)C-drug is measured by accelerator MS (AMS). In another article in this issue, a method validation is proposed where AMS was used as the analytical assay. Part of the validation is to assess the recovery of the analyte being measured as this has a direct impact on its quantification. In this article, a method of internal standardisation is described where the UV response of the nonlabeled analyte, spiked in excess into the matrix being analysed, is used for internal standardization. The method allows for the recovery of analyte to be measured in each individual sample being analysed. It is important to know the recovery of a (14)C-labeled analyte when determining its mass concentration from (14)C:(12)C isotopic ratio data using AMS. A method is reported in this article that utilizes the UV response of the nonlabeled drug for internal standardization, so that the recovery for each individual sample analyzed can be ascertained.

Developing trends in bioanalysis.

The Forum, initiated over 30 years ago by Eric Reid of the University of Surrey, after whom the Forum is now named, is held in Guildford at the University of Surrey every 2 years. This year's forum was the 18th in the series. There were over 30 oral presentations and more than 20 posters, together with suppliers' exhibitions on Tuesday and Wednesday. At its inception, the title of Forum, maintained over the years, was chosen to emphasize the interactive nature of the meeting; somewhere that practical issues could be discussed and successes and failures, 'tricks' of the trade, surprises and problems where logic (initially) fails are shared. The on-campus format and evening social events provide plenty of opportunity to discuss unresolved problems in a 'convivial' atmosphere. There were three major themes to this year's Forum: interpreting and implementing 'metabolites in safety testing'; quantification of biologicals (proteins and peptides, whether they be drugs, antidrug antibodies or biomarkers) in biological matrices using LC-MS/MS; and the use of dried blood spots. Interspersed among these were the core topics of the Forum, case histories illustrating the problem-solving skills of the bioanalyst and their ability to cope with surprises.