title: Rapid label-free determination of ketamine in whole blood using secondary ion mass spectrometry.
abstract: A fast and accurate drug screening to identify the possible presence of a wide variety of pharmaceutical and illicit drugs is increasingly requested in forensic and clinical toxicology. The current first-line screening relies on immunoassays. They determine only certain common drugs of which antibodies are commercially available. To address the issue, a rapid screening using secondary ion mass spectrometry (SIMS) has been developed. In the study, SIMS directly analyzed ketamine in whole blood without any pretreatment. While the untreated blood has a complicated composition, principal-components analysis (PCA) is used to detect unknown specimens by building up an analytical model from blank samples which were spiked with ketamine at 100 ng mL(-1), to simulate the presence of ketamine. Each characteristics m/z is normalized and scaled by multiplying the root square of intensity and square of corresponding m/z, developed by National Institute of Standards and Technology (NIST). Using linear regression and the result of PCA, this study enables to correctly distinguish ketamine positive and negative groups in an unknown set of specimens. The quantity of ketamine in an unknown set was determined using gas chromatography-mass spectrometry (GC-MS) as the reference methodology. Instead limited by commercially available antibodies, SIMS detects target molecules straight despite the label-free detection capabilities of SIMS, additional data processing (here, PCA) can be used to fully analyse the produced data, which extends the range of analytes of interest on drug screening. Furthermore, extremely low sample volume, 5 µL, is required owing to the high spatial resolution of SIMS. In addition, while the whole blood is analyzed within 3 min, the whole analysis has been shortened significantly and high throughput can be achieved.
authors.affiliation: Research Center for Applied Sciences, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Hua-Yang
authors.initials: HY
authors.lastname: Liao
authors.affiliation: Forensic and Clinical Toxicology Center, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 100, Taiwan; Graduate Institute of Toxicology, National Taiwan University College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Jung-Hsuan
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Research Center for Applied Sciences, Academia Sinica, Taipei 115, Taiwan; Department of Materials Science and Engineering, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Jing-Jong
authors.initials: JJ
authors.lastname: Shyue
authors.affiliation: Forensic and Clinical Toxicology Center, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 100, Taiwan; Department and Graduate Institute of Forensic Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Chia-Tung
authors.initials: CT
authors.lastname: Shun
authors.affiliation: Graduate Institute of Toxicology, National Taiwan University College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Huei-Wen
authors.initials: HW
authors.lastname: Chen
authors.affiliation: Department and Graduate Institute of Forensic Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Su-Wei
authors.initials: SW
authors.lastname: Liao
authors.affiliation: Department and Graduate Institute of Forensic Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Chih-Kang
authors.initials: CK
authors.lastname: Hong
authors.affiliation: Forensic and Clinical Toxicology Center, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 100, Taiwan; Department and Graduate Institute of Forensic Medicine, National Taiwan University, Taipei 100, Taiwan. Electronic address: paishanchen@ntu.edu.tw.
authors.forename: Pai-Shan
authors.initials: PS
authors.lastname: Chen
mesh_terms: D001774:Blood Chemical Analysis / Q000379:methods*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007649:Ketamine / Q000097:blood*; D015999:Multivariate Analysis; D018629:Spectrometry, Mass, Secondary Ion / Q000379:methods*; D013997:Time Factors
chemical_list: D007649:Ketamine
keywords: Drug screening; Gas chromatography–mass spectrometry (GC–MS); Ketamine; Principal-components analysis (PCA); Secondary ion mass spectrometry (SIMS); Whole blood