Bioanalysis of acetylcarnitine in cerebrospinal fluid by HILIC–mass spectrometry

Abstract

Acetyl-L-carnitine (ALCAR) is a potential biomarker for the modulation of brain neurotransmitter activity, but is also present in cerebrospinal fluid (CSF). Recent studies have utilized hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) based assays to detect and quantify ALCAR within biofluids such as urine, plasma and serum, using various sample pretreatment procedures. In order to address the need to quantify ALCAR in CSF on a high-throughput scale, a new and simple HILIC-MS/MS assay has been successfully developed and validated. For rapid analysis, CSF sample pretreatment was performed via 'dilute and shoot' directly onto an advanced HILIC column prior to MS/MS detection. This newly developed HILIC-MS/MS assay shows good recoveries of ALCAR without the need for chemical derivatization and multistep sample extraction procedures. The employment of this assay is suitable for the high-throughput bioanalysis and quantification of ALCAR within the CSF of various animal models and human clinical studies.

Automated Real-Time Tumor Pharmacokinetic Profiling in 3D Models: A Novel Approach for Personalized Medicine

“…UHPLC-MS/MS again proved as the method of choice as it was already useful for a wide range of applications in pharmacology, toxicology, and forensics [ 31 , 32 , 33 ]. Despite first dilute and inject attempts to reduce the time-consuming sample preparation [ 34 , 35 , 36 , 37 , 38 , 39 ], UHPLC-MS/MS analyses still often utilizes extensive sample preparation to separate the molecule of interest from interfering proteins and potential enzymatic degradation processes [ 40 ]. Our method (A) used for quantitation of docetaxel was successfully validated in terms of selectivity, carry-over, lower limit of quantitation (LLOQ), calibration function, accuracy, and precision according to EMA guidelines for bioanalytical method validation.…”