MSACL 2016 US Abstract

Multichannel Optimization of a New Four Channel HPLC with a Single Mass Spectrometer to Simplify Workflow Complexity and to Improve Throughput of LC-MS

Jason Lai (Presenter)
Thermo Fisher Scientific

Bio: Jason Lai, Ph.D., MBA, is the Regulated Product Manager of LSMS Translational Research/IVD/Toxicology department of Chromatography and Mass Spectrometry Division at Thermo Fisher Scientific. His industrial experiences include clinical diagnostics, medical device, toxicology (clinical & forensic), newborn screening, diabetes monitoring, point-of-care, life science and biotechnology. He has served various roles in marketing, product development, product management, market and business development, and R&D. In addition to 20 peer-reviewed journal articles, he has made more than 50 presentations internationally in various topics of clinical diagnostics and related technologies.

Authorship: Jason Lai, Jia Wang, Brad Hart, Kristine Van Natta, Goli Fahid, Thai Ho, Marta Kozak, Jorge Valdivia, Haibo Wang, Erkan Diri
Thermo Fisher Scientific

Short Abstract

There are four things that matter the most to routine clinical lab operation: the quality of test results, the efficiency of generating those results, the turn-around time to report the results and how much it costs to do all this. Currently, clinical laboratories are facing challenges in handling a large number of samples with crowded lab space and shortage of experienced staff. We address clinical labs’ concerns for speed, efficiency, flexibility and laboratory space restrictions with a compact four-channel HPLC, tandem mass spectrometry and software that streamlines LC-MS workflow. For in vitro diagnostic use. Not available in all countries.

Long Abstract

Introduction

There are four things that matter the most to routine clinical lab operation: the quality of test results, the efficiency of generating those results, the turn-around time to report the results and how much it costs to do all this. Currently, clinical laboratories are facing challenges in handling a large number of samples with crowded lab space and shortage of experienced staff. We address clinical labs’ concerns for speed, efficiency, flexibility and laboratory space restrictions with a compact four-channel HPLC, tandem mass spectrometry and software that streamlines LC-MS workflow.

When analytes elute for only a portion of an HPLC run, mass spectrometers configured in a single channel LC-MS workflow may only be in use in a fraction of the method time. A new HPLC brings the productivity of up to four HPLC channels to a single mass spectrometer, four times the samples can be run, maximizing the LC-MS output. With built-in multichannel optimization software, up to four identical or different test methods can run, and simplify workflow. We evaluated a prototype unit of a new four channels HPLC with a new Tandem-MS.

Methods

This HPLC instrument has four LC channels. The channels have separate injectors, tubing, heaters, pumps, columns, and solvents. The channels are synchronized to a single mass spectrometer. Each channel operates independently, allowing four identical or different tests to run simultaneously. In addition, identical or different analytical columns and mobile phases can be used with each channel, providing method flexibility. Cross-sequential optimization ensures the maximum performance of the mass spectrometer with little to no idle time. When four channels run simultaneously, the data collection times are scheduled with staggered starts so that the data collections do not occur at the same time.

In this study, calibration Standards, stable isotopically labeled Internal Standards (IS), QC sample and test sample were spiked in synthetic urine. Tandem MS was operated in selected reaction monitor (SRM) mode with heated electrospray ionization (HESI) positive ion mode, and specific SRM transitions of precursor ion to product ion were selected for identification and quantitation of each compound.

Evaluation of an Identical Method on Four Channels

A test mixture of four example compounds (Atenolol, Warfarin, Lidocaine, Imipramine) in synthetic urine were analyzed (dilute and shoot) in four HPLC channels. Each HPLC channel used the same liquid chromatographic elution method, the same composition of binary mobile phases (aqueous and methanol buffers) from its own solvent bottles, and the same type of analytical column (Thermo Scientific™ Accucore PFP; 50 x 2.1mm, 2.6 µm). A total of 1976 samples were run unattended and continuously for about 60 hours. QC samples were inserted in every 30 samples for each channel.

Evaluation of Four Different Methods on Four Channels

A precision study was conducted with four different methods using this four channel HPLC (n=40 for each channel; 10 replicates per run, 4 runs per channel). In this study, identical mobile phases (aqueous buffer/methanol buffer) and identical analytical columns (Accucore PFP; 50 x 2.1mm, 2.6 µm) were used for each channel. Each HPLC channel ran with a different HPLC elution method and a different set of example compounds. As shown in the list below, a different test mixture of example compounds in synthetic urine was analyzed (dilute and shoot) for each HPLC channel.

Channel 1: Atenolol, Warfarin, Lidocaine, Imipramine

Channel 2: Amphetamine, Methamphetamine

Channel 3: Alprazolam, alpha-hydroxyalprazolam

Channel 4: Oxycodone, Noroxycodone

Results

The preliminary test results showed that RSD’s of all test example compounds were less than 5% in retention time, and less than 10% in concentration measurements. The test results also demonstrated that this four channel HPLC can continuously run tests unattended for about 60 hours. In addition to pre-process samples, samples of less complex matrices can be injected directly with a dilute-and-shoot process.

Conclusion

This four-channel HPLC demonstrated each channel can operate independently, up to four identical or different test methods can run, maximizing method flexibility. In addition, the built-in software automatically optimizes operation of the channels, increases the utilization of mass spectrometer time with little idle time.

For in vitro diagnostic use. Not available in all countries.


References & Acknowledgements:


Financial Disclosure

DescriptionY/NSource
Grantsno
SalaryyesThermo Fisher Scientific
Board Memberno
Stockno
Expensesno

IP Royalty: no

Planning to mention or discuss specific products or technology of the company(ies) listed above:

yes