Sense and nonsense. Analysts are constrained certainly but good analytical science is good analytical science. During the method development stage several parameters are examined.
One parameter for example is recovery of analyte from a set of spiked individual (matrices). Another exercise is the recovery of material from spiked matrix after exposure to a number of stability challenging conditions, e.g., freeze thaw. During these tests it is certainly possible to "find less or, even "none" of the response(s) to the analyte(s). Analysts would then "improve" the assay using a number of techniques including the addition of preservatives or specifying the handling and storage conditions. Too often however, the clinical collection parameters may have been defined before the conclusion or event the start of analytical method development and perhaps "if pushed too far and incessantly" the analyst will release "nonsense data" or instrument responses free of "interpretation". For people at the next rung to use data this in any rational way suggests that those people should perhaps be using a seer rather than an analyst. When they are stung by the results of their data analysis, they will immediately revert and "blame" the analyst (or if they do not, regulatory agencies will) for releasing "bad" data. PK/PD and Analytical scientists usually work together during the analytical process. PK/PD driving with LLOQ, suggesting metabolites, Analytical providing the best approach to meet that requirement including meeting all current method validation and reporting guidelines. Edward F. O'Connor, PhD 78 Marbern Drive Suffield, CT 06078 Tel 860-668=6201 Cel 860-324-6780 efocon...@cox.net Edward F. O'Connor, PhD 78 Marbern Drive Suffield, CT 06078 Tel 860-668=6201 Cel 860-324-6780 efocon...@cox.net -----Original Message----- From: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] On Behalf Of Stephen Duffull Sent: Monday, August 24, 2009 4:18 AM To: Nick Holford; nmusers Subject: RE: [NMusers] Honest measurements Mats I agree with Nick. Negative "observed" concns do occur for assays, even in my limited time working with HPLC I have seen them, however due to LOD/LOQ they are never really looked for and certainly never reported... Steve > -----Original Message----- > From: owner-nmus...@globomaxnm.com [mailto:owner- > nmus...@globomaxnm.com] On Behalf Of Nick Holford > Sent: Monday, 24 August 2009 6:25 p.m. > To: nmusers > Subject: [NMusers] Honest measurements > > > > Mats Karlsson wrote: > > << Chemists, however pushed, would never report negative > concentrations, not > for past studies, not for future studies. The methods they use don't > even > report them.>> > > I am working with a chemist using LC/MS who has been persuaded to look > honestly at his data without preconceived ideas of limits of > quantitation and detection. Indeed when he opened his eyes he found > that his system was indeed giving negative concentration measurements > (at times when concentrations were expected to be very low). > > Of course we must do other things when the data is censored by bad > scientific practice in the chemist's lab but with honest measurments an > additive residual error model is required. > > Nick > > > -- > Nick Holford, Professor Clinical Pharmacology > Dept Pharmacology & Clinical Pharmacology > University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New > Zealand > n.holf...@auckland.ac.nz tel:+64(9)923-6730 fax:+64(9)373-7090 > mobile: +64 21 46 23 53 > http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford No virus found in this incoming message. Checked by AVG - www.avg.com Version: 8.5.409 / Virus Database: 270.13.65/2322 - Release Date: 08/23/09 18:03:00
