Sensitive screening of abused drugs in dried blood samples using ultra-high-performance liquid chromatography-ion booster-quadrupole time-of-flight mass spectrometry

Divyabharathi Chepyala; I-Lin Tsai; Hsiao-Wei Liao; Guan-Yuan Chen; Hsi-Chun Chao; Ching-Hua Kuo

doi:10.1016/j.chroma.2017.02.037

Sensitive screening of abused drugs in dried blood samples using ultra-high-performance liquid chromatography-ion booster-quadrupole time-of-flight mass spectrometry

J Chromatogr A. 2017 Mar 31:1491:57-66. doi: 10.1016/j.chroma.2017.02.037. Epub 2017 Feb 21.

Authors

Divyabharathi Chepyala¹, I-Lin Tsai², Hsiao-Wei Liao¹, Guan-Yuan Chen¹, Hsi-Chun Chao¹, Ching-Hua Kuo³

Affiliations

¹ School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; The Metabolomics Core Laboratory, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan.
² Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
³ School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; The Metabolomics Core Laboratory, Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan; Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: kuoch@ntu.edu.tw.

PMID: 28238428
DOI: 10.1016/j.chroma.2017.02.037

Abstract

An increased rate of drug abuse is a major social problem worldwide. The dried blood spot (DBS) sampling technique offers many advantages over using urine or whole blood sampling techniques. This study developed a simple and efficient ultra-high-performance liquid chromatography-ion booster-quadrupole time-of-flight mass spectrometry (UHPLC-IB-QTOF-MS) method for the analysis of abused drugs and their metabolites using DBS. Fifty-seven compounds covering the most commonly abused drugs, including amphetamines, opioids, cocaine, benzodiazepines, barbiturates, and many other new and emerging abused drugs, were selected as the target analytes of this study. An 80% acetonitrile solvent with a 5-min extraction by Geno grinder was used for sample extraction. A Poroshell column was used to provide efficient separation, and under optimal conditions, the analytical times were 15 and 5min in positive and negative ionization modes, respectively. Ionization parameters of both electrospray ionization source and ion booster (IB) source containing an extra heated zone were optimized to achieve the best ionization efficiency of the investigated abused drugs. In spite of their structural diversity, most of the abused drugs showed an enhanced mass response with the high temperature ionization from an extra heated zone of IB source. Compared to electrospray ionization, the ion booster (IB) greatly improved the detection sensitivity for 86% of the analytes by 1.5-14-fold and allowed the developed method to detect trace amounts of compounds on the DBS cards. The validation results showed that the coefficients of variation of intra-day and inter-day precision in terms of the signal intensity were lower than 19.65%. The extraction recovery of all analytes was between 67.21 and 115.14%. The limits of detection of all analytes were between 0.2 and 35.7ngmL^-1. The stability study indicated that 7% of compounds showed poor stability (below 50%) on the DBS cards after 6 months of storage at room temperature and -80°C. The reported method provides a new direction for abused drug screening using DBS.

Keywords: Dried blood spots; Drug of abuse; Ion-booster; Quadrupole time-of-flight mass spectrometry; Ultra-high-performance liquid chromatography.

MeSH terms

Chromatography, High Pressure Liquid / methods*
Dried Blood Spot Testing / methods*
Humans
Illicit Drugs / blood*
Limit of Detection
Mass Spectrometry / methods*
Reproducibility of Results

Substances

Illicit Drugs