Therapeutic drug monitoring and LC–MS/MS

Adaway, Jo; Keevil, Brian

doi:10.1016/j.jchromb.2011.09.041

Cited by 128 publications

(93 citation statements)

References 249 publications

(171 reference statements)

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“…This method is based on high affinity for phospholipids, with low selectivity toward a wide range of basic, neutral, and acidic compounds. 12) We systematically compared the simple protein precipitation procedure to the new sample preparation platform and observed significant improvement in the bioanalysis. Because omeprazole is unstable in acidic solution, we employed acetonitrile for extraction in the Ostro sample preparation procedure instead of acidified acetonitrile, which is recommended to use in the standard protocol.…”

Section: Lc-ms/ms Methods Developmentmentioning

confidence: 99%

Simultaneous LC-MS/MS Analysis of the Plasma Concentrations of a Cocktail of 5 Cytochrome P450 Substrate Drugs and Their Metabolites

Tanaka

Uchida

Inui

et al. 2014

Biological & Pharmaceutical Bulletin

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A "cocktail" approach, which involves simultaneous administration of multiple CYP-specific probes, concurrently detects the activity of multiple CYP enzymes. We developed and validated a rapid and selective LC-MS/MS method for determining the plasma concentrations of 5 CYP probe drugs and metabolites (caffeine/paraxanthine, CYP1A2 substrate; losartan/losartan carboxylic acid (E3174), CYP2C9 substrate; omeprazole/5-hydroxyomeprazole, CYP2C19 substrate; dextromethorphan/dextrorphan, CYP2D6 substrate; and midazolam/1′-hydroxymidazolam, CYP3A4 substrate) by single-step extraction, followed by a single LC-MS/MS run. An Ostro 96-well plate was used for extraction of CYP substrates and metabolites from human plasma and urine. Following optimization of the chromatographic conditions, all the peaks were well separated, and retention times ranged between 4.4 and 11.7 min. The total run time for a single injection was within 13 min. The accuracy and precision values suggested that the assay had high accuracy and reliability in plasma and urine samples. No significant matrix interference was observed. To demonstrate the efficacy of this method, plasma and urine concentrations of 5 CYP probe substrates and their metabolites were determined after simultaneous oral administration of 5 drugs to 4 healthy volunteers. All the substrates and metabolites were detected over an 8 h period, and the plasma concentrations of each substrate at 8 h after administration were above the lower limit of quantification. Urine concentrations of drugs and their metabolic ratio were evaluated after the administration. In conclusion, the advantage of our cocktail approach is that it enables in vivo assessment of the activity of various drug-metabolizing enzymes in a single assay. Key words cytochrome P450; cocktail; LC-MS/MS; healthy volunteerThe CYP system, which constitutes the major drug-metabolizing machinery in humans, catalyzes the biotransformation of xenobiotics and has been reported to process over 90% of the currently marketed drugs.1,2) The drug-metabolizing activities of different CYP isoforms show high inter-and intraindividual variations; age, gender, genetics, environmental factors, dietary components, and endogenous mediators contribute to this variability. [3][4][5] In addition, certain medications can induce or inhibit the activity of drug-metabolizing enzymes, resulting in drug-drug interactions. Variation in CYP activity results in variation in the pharmacokinetics of its substrates, which in turn may alter the pharmacodynamics of these drugs. Thus, predicting the pharmacokinetics and pharmacodynamics of the drug substrates of CYP is important for predicting potential drug interactions and for CYP substrate dose optimization.A "cocktail" approach concurrently detects the activity of multiple CYP enzymes and involves simultaneous administration of multiple CYP-specific probes followed by the evaluation of their pharmacokinetics in a single experiment. Since the Pittsburgh cocktail was first introduced in 1997, 6) several cocktail...

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Section: Lc-ms/ms Methods Developmentmentioning

confidence: 99%

Simultaneous LC-MS/MS Analysis of the Plasma Concentrations of a Cocktail of 5 Cytochrome P450 Substrate Drugs and Their Metabolites

Tanaka

Uchida

Inui

et al. 2014

Biological & Pharmaceutical Bulletin

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“…The analytical specificity of MS-based immunosuppressant assays is also superior to that of existing immunoassays, which can overestimate the concentration of these medications because of the variable cross-reactivity with immunosuppressant metabolites (32)(33)(34). Lastly, there is now one FDA-approved MS tacrolimus assay (WatersMassTrak®) and several commercially available MS kits with IVD (in vitro diagnostic)-CE certification for the measurement of immunosuppressants (ChromsystemsMassTox®, Recipe-ClinMass®, and Waters-MassTrak®), which make MS-based assays more attractive for smaller laboratories with less expertise (35 ).…”

Section: Advantages Of Msmentioning

confidence: 99%

Effective Use of Mass Spectrometry in the Clinical Laboratory

2016

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BACKGROUND:Historically the success of mass spectrometry in the clinical laboratory has focused on drugs of abuse confirmations, newborn screening, and steroid analysis. Clinical applications of mass spectrometry continue to expand, and mass spectrometry is now being used in almost all areas of laboratory medicine.CONTENT: A brief background of the evolution of mass spectrometry in the clinical laboratory is provided with a discussion of future applications. Prominent examples of mass spectrometry are covered to illustrate how it has improved the practice of medicine and enabled physicians to provide better patient care. With increasing economic pressures and decreasing laboratory test reimbursement, mass spectrometry testing has been shown to provide cost-effective solutions. In addition to pointing out the numerous benefits, the challenges of implementing mass spectrometry in the clinical laboratory are also covered.

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“…It is recent developments in LC-MS technology that has laid the ground for the successful use of mass spectrometry methods in clinical laboratories (18,19). The development of chromatography using sub 2 µm particles has given increased resolution power and shortened analysis times (20).…”

Section: Mass Spectrometrymentioning

confidence: 99%

Can Pharmacometabolomics and LC-HRMS develop a new Concept for Therapeutic Drug Monitoring?

Beck¹

2015

J Appl Bioanal

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Therapeutic drug monitoring and LC–MS/MS

Cited by 128 publications

References 249 publications

Simultaneous LC-MS/MS Analysis of the Plasma Concentrations of a Cocktail of 5 Cytochrome P450 Substrate Drugs and Their Metabolites

Simultaneous LC-MS/MS Analysis of the Plasma Concentrations of a Cocktail of 5 Cytochrome P450 Substrate Drugs and Their Metabolites

Effective Use of Mass Spectrometry in the Clinical Laboratory

Can Pharmacometabolomics and LC-HRMS develop a new Concept for Therapeutic Drug Monitoring?

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