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Shen-An Chan

Bio: Shen-An Chan is an academic researcher from Agilent Technologies. The author has contributed to research in topics: Matrix (chemical analysis) & Detection limit. The author has an hindex of 1, co-authored 1 publications receiving 32 citations.

Papers
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Journal ArticleDOI
20 Sep 2010-Analyst
TL;DR: Chip-HPLC-MS system can be utilized for the determination of small molecules such as drug metabolites and neurotransmitters in biological fluids for clinical diagnosis and exhibited high correlation between 7-aminoFM2 spiked Milli-Q water and 7-AMinoFM 2 spiked urine samples.
Abstract: Microfluidic chip-based high-performance-liquid-chromatography coupled to mass spectrometry (chip-HPLC-MS) has been widely used in proteomic research due to its enhanced sensitivity. We employed a chip-HPLC-MS system for determining small molecules such as drug metabolites in biological fluids. This chip-HPLC-MS system integrates a microfluidic switch, a 2-dimensional column design including an enrichment column (160 nL) for sample pre-concentration and an analytical column for chromatographic separation, as well as a nanospray emitter on a single polyimide chip. In this study, a relatively large sample volume (500 nL) was injected into the enrichment column for pre-concentration and an additional 4 μL of the initial mobile phase was applied to remove un-retained components from the sample matrix prior to chromatographic separation. The 2-dimensional column design provides the advantages of online sample concentration and reducing matrix influence on MS detection. 7-Aminoflunitrazepam (7-aminoFM2), a major metabolite of flunitrazepam (FM2), was determined in urine samples using the integrated chip-HPLC-MS system. The linear range was 0.1–10 ng mL−1 and the method detection limit (signal-to-noise ratio of 3) was 0.05 ng mL−1 for 7-aminoFM2. After consecutive liquid–liquid extraction (LLE) and solid-phase extraction (SPE), the chip-HPLC-MS exhibited high correlation between 7-aminoFM2 spiked Milli-Q water and 7-aminoFM2 spiked urine samples. This system also showed good precision (n = 5) and recovery for spiked urine samples at the levels of 0.1, 1.0, and 10 ng mL−1. Intra-day and inter-day precision were 2.0–7.1% and 4.3–6.0%, respectively. Clinical urine samples were also analyzed by this chip-HPLC-MS system and acceptable relative differences (−1.3 to −13.0%) compared with the results using a GC-MC method were determined. Due to its high sensitivity and ease of operation, the chip-HPLC-MS system can be utilized for the determination of small molecules such as drug metabolites and neurotransmitters in biological fluids for clinical diagnosis.

34 citations


Cited by
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TL;DR: The advances of Chip-MS in the past decade are reviewed, covering innovations in microchip fabrication, microchips coupled to electrospray ionization (ESI)-MS and matrix-assisted laser desorption/ionization (MALDI)-MS.
Abstract: Microfluidic technology has shown advantages of low sample consumption, reduced analysis time, high throughput, and potential for integration and automation. Coupling microfluidic chips to mass spectrometry (Chip-MS) can greatly improve the overall analytical performance of MS-based approaches and expand their potential applications. In this article, we review the advances of Chip-MS in the past decade, covering innovations in microchip fabrication, microchips coupled to electrospray ionization (ESI)-MS and matrix-assisted laser desorption/ionization (MALDI)-MS. Development of integrated microfluidic systems for automated MS analysis will be further documented, as well as recent applications of Chip-MS in proteomics, metabolomics, cell analysis, and clinical diagnosis.

109 citations

Journal ArticleDOI
TL;DR: The development of a method coupling microfluidics and a miniature mass spectrometer, applied to quantitation of drugs of abuse in urine that can be quantified from four samples in less than 15 min from (dried) sample to analysis is reported.
Abstract: We report the development of a method coupling microfluidics and a miniature mass spectrometer, applied to quantitation of drugs of abuse in urine. A custom digital microfluidic system was designed to deliver droplets of solvent to dried urine samples and then transport extracted analytes to an array of nanoelectrospray emitters for analysis. Tandem mass spectrometry (MS/MS) detection was performed using a fully autonomous 25 kg instrument. Using the new method, cocaine, benzoylecgonine, and codeine can be quantified from four samples in less than 15 min from (dried) sample to analysis. The figures of merit for the new method suggest that it is suitable for on-site screening; for example, the limit of quantitation (LOQ) for cocaine is 40 ng/mL, which is compatible with the performance criteria for laboratory analyses established by the United Nations Office on Drugs and Crime. More importantly, the LOQ of the new method is superior to the 300 ng/mL cutoff values used by the only other portable analysis sy...

65 citations

Journal ArticleDOI
TL;DR: The developed sample preparation method coupled with the nano-HPLC-Chip- MS/MS method was able to reveal the presence of drugs in hairs from the drug abusers, with the enhanced sensitivity, compared with the conventional HPLC-MS/MS.
Abstract: A microfluidic chip based nano-HPLC coupled to tandem mass spectrometry (nano-HPLC-Chip-MS/MS) has been developed for simultaneous measurement of abused drugs and metabolites: cocaine, benzoylecgonine, cocaethylene, norcocaine, morphine, codeine, 6-acetylmorphine, phencyclidine, amphetamine, methamphetamine, MDMA, MDA, MDEA, and methadone in the hair of drug abusers. The microfluidic chip was fabricated by laminating polyimide films and it integrated an enrichment column, an analytical column and a nanospray tip. Drugs were extracted from hairs by sonication, and the chromatographic separation was achieved in 15 min. The drug identification and quantification criteria were fulfilled by the triple quardropule tandem mass spectrometry. The linear regression analysis was calibrated by deuterated internal standards with all of the R 2 at least over 0.993. The limit of detection (LOD) and the limit of quantification (LOQ) were from 0.1 to 0.75 and 0.2 to 1.25 pg/mg, respectively. The validation parameters including selectivity, accuracy, precision, stability, and matrix effect were also evaluated here. In conclusion, the developed sample preparation method coupled with the nano-HPLC-Chip-MS/MS method was able to reveal the presence of drugs in hairs from the drug abusers, with the enhanced sensitivity, compared with the conventional HPLC-MS/MS.

61 citations

Journal ArticleDOI
TL;DR: Being able to determine the TPMT activity before starting a treatment using 6-mercaptopurine, an optimized dosage can be applied to each patient and serious toxicity appearing within thiopurine treatment will be prevented.
Abstract: In this contribution, the great potential of surface enhanced Raman spectroscopy (SERS) in a lab-on-a-chip (LOC) device for the detection of analyte molecules in a complex environment is demonstrated. Using LOC-SERS, the enzyme activity of thiopurine S-methyltransferase (TPMT) is analysed and identified in lysed red blood cells. The conversion of 6-mercaptopurine to 6-methylmercaptopurine catalysed by TPMT is observed as it gives evidence for the enzyme activity. Being able to determine the TPMT activity before starting a treatment using 6-mercaptopurine, an optimized dosage can be applied to each patient and serious toxicity appearing within thiopurine treatment will be prevented.

57 citations

Journal ArticleDOI
TL;DR: This mini‐review summarizes the utilization of commercial chip‐based LC‐MS systems for determination of small molecules in bioanalytical applications, including drug metabolites and disease/tumor‐associated biomarkers in clinical samples as well as adsorption, distribution, metabolism, and excretion studies of APIs in drug discovery and development.
Abstract: The development and integration of microfabricated liquid chromatography (LC) microchips have increased dramatically in the last decade due to the needs of enhanced sensitivity and rapid analysis as well as the rising concern on reducing environmental impacts of chemicals used in various types of chemical and biochemical analyses. Recent development of microfluidic chip-based LC mass spectrometry (chip-based LC-MS) has played an important role in proteomic research for high throughput analysis. To date, the use of chip-based LC-MS for determination of small molecules, such as biomarkers, active pharmaceutical ingredients (APIs), and drugs of abuse and their metabolites, in clinical and pharmaceutical applications has not been thoroughly investigated. This mini-review summarizes the utilization of commercial chip-based LC-MS systems for determination of small molecules in bioanalytical applications, including drug metabolites and disease/tumor-associated biomarkers in clinical samples as well as adsorption, distribution, metabolism, and excretion studies of APIs in drug discovery and development. The different types of commercial chip-based interfaces for LC-MS analysis are discussed first and followed by applications of chip-based LC-MS on biological samples as well as the comparison with other LC-MS techniques.

55 citations