A rapid and fully-automated method for the quantitation of tricyclic antidepressants in serum using turbulent-flow liquid chromatography–tandem mass spectrometry

Breaud, Autumn; Harlan, Robert; Bussolo, Joseph M. Di; McMillin, Gwendolyn A.; Clarke, William

doi:10.1016/j.cca.2010.02.067

“…The article explores two discreet components of a pseudo-RMP as it would be applied clinically, namely the optimal concentration of internal standard to add and the requirement for measurement of the RF. The appropriate amount of internal standard was evaluated at final concentrations in samples that spanned the linear measureable range of the comparator assay (8 ). Surprisingly, good agreement was observed between the original result and the pseudo-RMP result for each of the 4 internal standard concentrations used.…”

mentioning

confidence: 99%

“…This agreement, while notable, is actually confounded by the process of discreet assignment and ignores imprecision in each assay. Further evaluation of categorical discordance between calibration protocols indicated that all samples were within 2 SDs of the comparator method (8 ), with absolute biases ranging from Ϫ20.4% to 9.6% (W. Clarke, personal communication, March 15, 2013). Allowing for acceptable assay imprecision (2SD) leads to 100% agreement for cRF and sRF compared to interpolated calibration, results that are quite remarkable.…”

mentioning

confidence: 99%

The March of the Masses

Grant

¹

2013

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The growth of mass spectrometry and more specifically liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) 2 continues to accelerate in the clinical laboratory. A recent publication (1 ) provides readers with the opportunity to see where we have been, offering examples of how LC-MS/MS has impacted diagnostic care (steroids and clinical toxicology); where we are (pain management, peptide hormones, and single proteins); and where we are going (protein panels, increased throughput and automation). The techniques and technologies discussed posit 3 conclusions. First, the potential scope of mass spectrometry testing in clinical chemistry is prospectively limitless. Second, the tools and technologies being deployed will require further refinement for mass spectrometers to become established automated clinical analyzers. Third, the promise of reference interval measurement in support of clinical measurement has been practically realized for some applications and is feasible for others.Two central tenets are evident in each application. First, the "killer app" of mass spectrometry incorporates the use of a stable labeled isotope of the analyte(s) being measured with various isotope dilution strategies for calibration. An ideal internal standard is both physiologically unique relative to the composition of the test specimen and physicochemically identical to the analyte, such that recovery, separation, and ionization in each specimen are controlled and corrected: the perfect analytical control for each specimen. Second, multiconcentration calibrators defining the analytical range, often bracketing QCs and samples, control for instrument response drift and deviations from detection linearity over the course of analysis. The combination of these two principles, coupled with the specificity of measurement that LC-MS/MS affords, provides the opportunity for reference level measurement. This, however, comes with historical baggage; LC-MS/MS is almost exclusively deployed in a batch mode of analysis in clinical laboratories.In this issue of Clinical Chemistry, Olson et al. (2 ) illuminate, illustrate, and iterate the viewpoint that the dogma of batch mode analysis is both outdated and unnecessarily burdensome. The practice of calibration curve analysis with each set of samples is derived from pharmaceutical drug development from the mid1990s. Application of LC-MS/MS, the gold standard technique, was hampered by the technologies of the time and adherence to guidance, consequently resulting in ultraconservative analytical methodologies (3 ). The constraint of daily or batch-specific calibration is most keenly felt in the clinical laboratory, particularly in smaller hospitals settings where STAT sample analysis is de rigueur and a single instrument is required to perform many different measurements on a diverse array of analytes within a single shift. The obvious need for random access LC-MS/MS systems is apparent (1 ), and Olson et al. provide insights and key details in the path toward this goal. Most importan...

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“…The combination of LC with matrix-assisted laser desorption ionization (MALDI) started to emerge in the mid-1990s 18,19 and continuous effort was undertaken to further improve the technique [20][21][22][23][24][25] . Very recently LC-MS methods were described using desorption electro spray ionization (DESI) 26 and direct analysis in real time (DART) 27,28 interfaces.…”

Section: Years Of Ms Instrumental Developments -Impact On Lc-ms/msmentioning

confidence: 99%

Lc/Ms:an Essential Tool in Drug Development

Baluguri¹,

Nama²,

Chandu³

et al. 2012

Int J of Adv in Phar Ana

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The combination of high-performance liquid chromatography and mass spectrometry (LC/MS) has had a sign cant impact on drug development over the past decade. Continual improvements in LC/MS interface technologies combined with powerful features for structure analysis, qualitative and quantitative, have resulted in a widened scope of application. These improvements coincided with breakthroughs in combinatorial chemistry, molecular biology, and an overall industry trend of accelerated development. The use of high-performance liquid chromatography combined with mass spectrometry (HPLC-MS) or tandem mass spectrometry (HPLC-MS-MS) has proven to be the analytical technique of choice for most assays used in various stages of new drug discovery. A summary of the key components of HPLC-MS systems, as well as an overview of major application areas that use this technique as part of the drug discovery process, will be described here. This review will also provide an introduction into the various types of mass spectrometers that can be selected for the multiple tasks that can be performed using LC-MS as the analytical tool. The strategies for optimizing the use of this technique and also the potential problems and how to avoid them will be highlighted.

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“…3. Types of mass spectrometers: 25 There are many types of mass spectrometers available for interfacing with HPLC 2 , one of the more common systems used for HPLC-MS is the single quadruple mass spectrometer; this system will provide a mass spectrum for each chromatographic peak that elutes from the LC column and is analysed by the MS system. The second type of system shown is the time-off light (TOF) mass spectrometer, which has the added capability of providing a higher mass resolution spectrum from each component that is assayed.…”

Section: Principles Of Lc-msmentioning

confidence: 99%

“…The combination of LC with matrix-assisted laser desorption ionization (MALDI) started to emerge in the mid-1990s 18,19 and continuous effort was undertaken to further improve the technique [20][21][22][23][24][25] . Very recently LC-MS methods were described using desorption electro spray ionization (DESI) 26 and direct analysis in real time (DART) 27,28 interfaces.…”

Section: Years Of Ms Instrumental Developments -Impact On Lc-ms/msmentioning

confidence: 99%

Lc/Ms:an Essential Tool in Drug Development

Baluguri¹,

Nama²,

Chandu³

et al. 2012

Int J of Adv in Phar Ana

View full text Add to dashboard Cite

The combination of high-performance liquid chromatography and mass spectrometry (LC/MS) has had a sign cant impact on drug development over the past decade. Continual improvements in LC/MS interface technologies combined with powerful features for structure analysis, qualitative and quantitative, have resulted in a widened scope of application. These improvements coincided with breakthroughs in combinatorial chemistry, molecular biology, and an overall industry trend of accelerated development. The use of high-performance liquid chromatography combined with mass spectrometry (HPLC-MS) or tandem mass spectrometry (HPLC-MS-MS) has proven to be the analytical technique of choice for most assays used in various stages of new drug discovery. A summary of the key components of HPLC-MS systems, as well as an overview of major application areas that use this technique as part of the drug discovery process, will be described here. This review will also provide an introduction into the various types of mass spectrometers that can be selected for the multiple tasks that can be performed using LC-MS as the analytical tool. The strategies for optimizing the use of this technique and also the potential problems and how to avoid them will be highlighted.

show abstract

A rapid and fully-automated method for the quantitation of tricyclic antidepressants in serum using turbulent-flow liquid chromatography–tandem mass spectrometry

Cited by 59 publications

References 33 publications

The March of the Masses

The March of the Masses

Lc/Ms:an Essential Tool in Drug Development

Lc/Ms:an Essential Tool in Drug Development

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