Direct, On-Site, On-Cartridge Toxicokinetic Sampling Prior to On-Line SPE: A Feasibility Study

Tump, Cornelis; Hilhorst, Martijn; Ooms, Jan Albert; Wieling, Jaap

doi:10.1365/s10337-003-0170-z

Cited by 3 publications

(3 citation statements)

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“…The sorbent sampling cartridge as used previously10 has been modified significantly to improve both ease of packing and absorption/desorption performance. Figure 1(B) shows a cartoon of the new sorbent sampling cartridge.…”

Section: Methodsmentioning

confidence: 99%

“…The cartridge is processed using standard equipment for on‐line SPE‐LC/MS/MS to analyze the blood sample. The new concept was termed ‘Sorbent Sampling’ and has been tested earlier for PK studies in rat 10. The objective of that study was the comparison of the sorbent sampling technique (SST) with conventional sampling (using a high‐performance liquid chromatography (HPLC) autosampler) for serum samples and showed good correlation.…”

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confidence: 99%

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Direct injection of whole blood for liquid chromatography/tandem mass spectrometry analysis to support single‐rodent pharmacokinetic studies

Ingelse¹,

Vogel²,

Botterblom³

et al. 2008

Rapid Comm Mass Spectrometry

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Mass spectrometric developments in the last decade enable (sub)nanomolar detection of drug compounds in biological matrices in a few microliters of blood. However, the sampling and especially the handling of these small blood volumes is not straightforward. We studied the feasibility of a recently developed 'sorbent sampling technique' to handle these small blood volumes and the application to support pharmacokinetic (PK) screening programs. This technique applies 5-10 microL of blood on a fibrous material packed into a cartridge. Blood samples absorbed on these cartridges are eluted directly, on-line onto a solid-phase extraction liquid chromatography/tandem mass spectrometry (SPE-LC/MS/MS) system. It is shown that the sorbent sampling technique can be applied for a range of drug compounds. In spite of issues with recovery and sample clean-up that need further improvement, the sorbent sampling technique provided similar data as compared to conventional analytics. The technique was successfully applied to derive kinetic data from individual mice, thereby decreasing the number of required mice for a PK study from 21 to 3.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Direct injection of whole blood for liquid chromatography/tandem mass spectrometry analysis to support single‐rodent pharmacokinetic studies

Ingelse¹,

Vogel²,

Botterblom³

et al. 2008

Rapid Comm Mass Spectrometry

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“…The use of plasma as the accepted matrix for bioanalytical studies was initiated by the limitations of the analytical techniques used in the early days of bioanalysis, although from a physiological point of view, whole blood (WB) would be the matrix of choice (Rowland and Emmons, ). The introduction of more sensitive techniques led to the opportunity to explore techniques like sorbent sampling (Tump et al , ), cell‐disintegrated blood sampling (Morello et al , ) and DBS sampling in (pre‐) clinical studies. It has been recognized that the collection of WB samples as DBS for PK studies offers a number of advantages over conventional plasma sampling, including finger or heel puncture, easy storage and easy shipment to analytical laboratories (no requirement for freezers and dry ice).…”

Section: Introductionmentioning

confidence: 99%

Application of dried blood spot sampling combined with LC-MS/MS for genotyping and phenotyping of CYP450 enzymes in healthy volunteers

Boer¹,

Wieling²,

Meulman³

et al. 2011

Biomed. Chromatogr.

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An early clinical development study (phase I) was conducted to determine the usefulness of dried blood spot (DBS) sampling as an alternative to venous sampling for phenotyping and genotyping of CYP450 enzymes in healthy volunteers. Midazolam (MDZ) was used as a substrate for phenotyping CYP3A4 activity; the concentrations of MDZ and its main metabolite 1'-hydroxymidazolam (1-OH MDZ) were compared between the DBS method from finger punctures, plasma and whole blood (WB), drawn by venipuncture, whereby several methodological parameters were studied (i.e. punch width, amount of dots analyzed and storage time stability). Genotyping between DBS and venous WB samples was compared for CYP2D6 (*3, *4, *6), CYP2C19 (*2, *3), CYP3A4 (*1B) and CYP3A5 (*3C). In addition, the subject's and phlebotomist's satisfaction with venous blood sampling compared with the DBS method was evaluated using a standardized questionnaire. An LC-MS/MS method for the quantification of the MDZ and 1-OH MDZ concentrations in DBS samples was developed and validated in the range of 0.100-100 ng/mL. No compromises were made for the limits of quantification of the DBS-LC-MS/MS method vs the authentic plasma and WB methods.

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Leveraging Advances inHPLCand Sample Preparation to MaximizeDMPKData Quality

Hayes

2012

Encyclopedia of Drug Metabolism and Interactions

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High throughput bioanalytical methods are essential to support the rapid discovery and development of drugs in the pharmaceutical industry. Liquid chromatography coupled with tandem mass spectrometric detection (LC‐MS/MS) is considered the benchmark analytical methodology to be employed for the quantification of new chemical entities in biological fluids. Because of the high sensitivity and selectivity of LC‐MS/MS, the time required for method development and subsequent sample analysis is dramatically reduced. Rigorous chromatographic resolutions of analytes and/or tedious sample extraction protocols are typically not required even when complex biological matrices are used. Nevertheless, effective sample preparation and appropriate chromatographic separation of endogenous matrix components is required to ensure the quality of the data. The importance of sample preparation stems from three major concerns: removing interferences from the biological sample matrices, concentrating analyte(s) of interest, and improving analytical system performance. The choice of sample preparation method should be dependent on the quality of the data required.

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Direct, On-Site, On-Cartridge Toxicokinetic Sampling Prior to On-Line SPE: A Feasibility Study

Cited by 3 publications

References 1 publication

Direct injection of whole blood for liquid chromatography/tandem mass spectrometry analysis to support single‐rodent pharmacokinetic studies

Direct injection of whole blood for liquid chromatography/tandem mass spectrometry analysis to support single‐rodent pharmacokinetic studies

Application of dried blood spot sampling combined with LC-MS/MS for genotyping and phenotyping of CYP450 enzymes in healthy volunteers

Leveraging Advances inHPLCand Sample Preparation to MaximizeDMPKData Quality

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