Highly Sensitive LC--MS--MS Analysis of a Pharmaceutical Compound in Human Plasma Using Monolithic Phase-Based On-line Extraction

Abstract

Monolithic columns have been used in recent years for fast chromatographic separation due to their high permeability and low backpressure. We have explored the potential of monolithic material as sample preparation tool in bioanalytical applications. By taking advantage of monolithic columns' online concentration capability, we have developed a highly sensitive liquid chromatography-tandem mass spectrometry assay for quantitative determination of a pharmaceutical compound in human plasma. The assay was fully validated to satisfy the requirements of precision and accuracy, selectivity, matrix effect, and reproducibility. A linear dynamic range from 0.011 ng/mL to 12.3 ng/mL was established as the calibration standard. The percentage of bias for quality control samples was between -9.9% and -2.5%. Coefficient of variation, a measurement of precision, was within 9.9%. On-line extraction with monolithic support provided adequate sample cleanup and on-line concentration of the analyte. The assay exhibited good tolerance to matrix effect and has been applied successfully to a clinical study. The incurred sample analysis showed that original and repeat values were within +/-10.1% for all assay samples.

Pharmacokinetics of the TRPV1 Antagonist ABT‐102 in Healthy Human Volunteers: Population Analysis of Data From 3 Phase 1 Trials

“…Plasma concentrations of ABT‐102 were determined using a validated liquid chromatography method with tandem mass spectrometric detection at Abbott Laboratories (Abbott Park, Illinois). A modified version of the bioanalytical method has been recently published, 30 and the reader is referred to this publication for details on the bioanalysis. The analytical method was validated over the concentration range of 0.08 to 134 ng/mL ( r 2 ≥ 0.994) with interrun variability (% coefficient of variation [CV]) and mean bias of less than 15%.…”

“…The study used an oral solution of ABT-102. Forty-five volunteers in general good health participated in this study in 5 dose groups (2,6,18,30, and 40 mg of ABT-102). Each group consisted of 9 participants; 6 received ABT-102, and 3 received placebo.…”

Monolith as a new sample preparation material: Recent devices and applications

“…This strategy was first applied to the extraction of phenols in an aqueous sample by Svec and co‐workers 49. Extraction using a monolith was first carried out on the basis of this approach, and many articles were published thereafter 49, 53–56, 61, 72–107. The published applications are listed in Tables 2–5.…”

A Phase 1 Study to Evaluate the Bioavailability and Food Effect of 2 Solid‐Dispersion Formulations of the TRPV1 Antagonist ABT‐102, Relative to the Oral Solution Formulation, in Healthy Human Volunteers

“…Plasma concentrations of ABT‐102 were determined using a validated liquid chromatography method with tandem mass spectrometric detection at Abbott Laboratories (Abbott Park, Illinois). Details of the bioanalytical methods can be found in Xu et al, 16 except that in the current study, an API 4000 tandem mass spectrometer with Analyst 1.3.2 software (Applied Biosystems, Foster City, California) was used. For the present study, the bioanalytical method was validated over the concentration range of 0.2 to 120 ng/mL ( r 2 ≥ 0.997) with interrun variability (% coefficient of variation [CV]) of less than 3.6% and mean bias between −1.3% and 0%.…”