Identification and reduction of ion suppression effects on pharmacokinetic parameters by polyethylene glycol 400.
Ion suppression in mass spectrometry has been described recently in detail and should always be considered during analysis by liquid chromatography/tandem mass spectrometry (LC/MS/MS) in a drug metabolism and pharmacokinetics (DMPK) environment. At best, ion suppression leads to decreased sensitivity but at worst could lead to incorrectly determined pharmacokinetic (PK) parameters. Our investigations centred on polyethylene glycol (PEG 400), an excipient often used in pre-clinical dosing vehicles. PEG was also found to be present in large quantities in the blood collection tubes used for pre-clinical PK studies. Ion suppression was observed for many analytes, either due to the use of PEG in the dosing vehicle or in blood collection tubes. The elimination of large ion suppression effects was attained by simple chromatographic gradient changes and the use of alternative blood collection tubes. The effect of the above was to increase the detected plasma concentration levels, which resulted in a change in key PK parameters.
Weaver
Richard
R
Physical & Metabolic Science, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough LE11 5RH, UK. Richard.Weaver1@astrazeneca.com
Riley
Rob J
RJ
D000818:Animals; D016477:Artifacts; D002851:Chromatography, High Pressure Liquid; D004353:Drug Evaluation, Preclinical / Q000379:methods* / Q000592:standards; D005079:Excipients / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics*; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry
D005079:Excipients; D004364:Pharmaceutical Preparations; D011092:Polyethylene Glycols