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. 2019 Jun 4;91(11):6986-6990.
doi: 10.1021/acs.analchem.9b01694. Epub 2019 May 17.

High-Precision Quantitation of Biofluid Samples Using Direct Mass Spectrometry Analysis

Wenpeng Zhang  1   2 , Yue Ren  3 , Ziqing Lin  3 , Zheng Ouyang  1   2   3
Affiliations

High-Precision Quantitation of Biofluid Samples Using Direct Mass Spectrometry Analysis

Wenpeng Zhang et al. Anal Chem. .

Abstract

The transition of mass spectrometry for clinical analysis is highly desirable, and major progress has been made with direct sampling ionization for operation simplification. High-precision quantitation, however, remains a major challenge in this transition. Herein, a novel method was developed for direct quantitation of biofluid samples, using an extremely simplified procedure for incorporation of internal standards selected against the traditional rules. Slug flow microextraction was used for the development, with conditions predicted by a theoretical model, viz., using internal standards of partition coefficients very different from the analytes and large sample-to-extraction solvent volume ratios. Direct quantitation of drug compounds in urine and blood samples was demonstrated. This development enabled an extremely simplified protocol that is expected to have a significant impact on on-site or clinical analysis.

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Figures

Figure 1.
Figure 1.
a) Slug flow microextraction of analytes from a sample of large volume; b) MS/MS spectra of 50 ng/mL verapamil in urine of 5 μL and 2000 μL using slug flow extraction followed by nanoESI MS analysis.
Figure 2.
Figure 2.
Three-dimension schematic showing the analyte/IS intensity ratio predicted for measurements as functions of the analyte/IS partitioning factor ratio and the sample/extraction solvent volume ratio.
Figure 3.
Figure 3.
a) SFME bulk sampling for detection morphine (logP = 0.87) at 500 ng/mL in urine samples of 0.5, 2 and 5 mL, extraction solvent ethyl acetate containing 10 ng/mL verapamil (logP = 3.8). Product ion intensity ratio of morphine (m/z 201.1) and verapamil (m/z 165.1) were recorded. b) Calibration curve for quantitative analysis of cotinine in urine (50–400 ng/mL) using SFME bulk sampling. Ethyl acetate with verapamil 10 ng/mL as IS was used as extraction solvent.
Figure 4.
Figure 4.
Calibration curve for analysis of lincomycin in blood (10–1000 ng/mL) using SFME bulk sampling. Ethyl acetate with amitriptyline 100 ng/mL as IS was used as extraction solvent.
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