Rapid quantification of acetaminophen in plasma using solid‐phase microextraction coupled with thermal desorption electrospray ionization mass spectrometry

Abstract

Rationale Solid‐phase microextraction coupled with thermal desorption electrospray ionization tandem mass spectrometry (SPME‐TD‐ESI‐MS/MS) is proposed as a novel method for the rapid quantification of acetaminophen in plasma samples from a pharmacokinetics (PK) study. Methods Traces of acetaminophen were concentrated on commercial fused‐silica fibers coated with a polar polyacrylate (PA) polymer using direct immersion SPME. No agitation, heating, addition of salt, or adjustment of the pH of the sample solution was applied during the extraction. Any acetaminophen absorbed on the SPME fibers was subsequently desorbed and detected by TD‐ESI‐MS/MS. Results Parameters of the absorption, sensitivity, reproducibility, and linearity for the SPME‐TD‐ESI‐MS/MS method were evaluated. The time required to complete a TD‐ESI‐MS/MS analysis was less than 30 seconds. Matrix‐matching calibration was performed to calculate the concentration of acetaminophen in the sample. A linear calibration curve with a concentration range of 100–10,000 ng/mL was constructed to calculate the quantity of acetaminophen. The SPME‐TD‐ESI‐MS quantification results for acetaminophen in plasma were in good agreement with those obtained by the conventional LC/MS/MS method. Conclusions With the proposed method, a 10‐min SPME time was enough to achieve the lower limit of quantitation (i.e. 100 ng/mL) and for a complete PK profiling of acetaminophen. A shorter extraction time could be achieved by applying agitation, heating, adding salt, or adjusting the pH of the sample solution to enhance analyte absorption efficiency. The time required to detect acetaminophen on the SPME fiber was less than 30 s, allowing the rapid quantification of acetaminophen in plasma with good accuracy.

Spherical Sampler Probes Enhance the Robustness of Ambient Ionization Mass Spectrometry for Rapid Drugs Screening

“…The R 2 value was 0.98 in solvent and 0.98 in blood over the concentration range of 50–2750 ng/mL, which is tolerable for a rough concentration estimation and confirms the linear response of an analytical signal from concentration. This achieved linear range is comparable to the previously described method of solid-phase microextraction coupled with thermal desorption electrospray ionization mass spectrometry [ 40 ] and shows the suitability of the described method with a porous sampler probe for direct analysis of raw biological samples.…”

“…A linear dynamic concentration range varied in the range of 2 to 3 orders of magnitude ( Figure S7 in Supplementary Materials ). These results are in good agreement with the therapeutic concentrations range, demonstrating the method’s suitability for therapeutic monitoring of drugs in biological matrices [ 41 ] and comparable with conventional methods, such as LC-MS/MS [ 42 , 43 , 44 ], or methods with preliminary extraction [ 40 ]. Matrix effects for APAP were calculated for two concentrations, 250 ng/mL (80.5%) and 2000 ng/mL (79.8%), and for diclofenac were 250 ng/mL (101.2%) and 2000 ng/mL (122.9%).…”

The study of distribution of ingested terbinafine on skin with ambient ionization tandem mass spectrometry

“…The detection limits of TD-ESI/MS for common organic compounds are within sub-ppm levels in full scan mode, and ppb levels in multiple reaction monitoring (MRM) mode [ 37 ]. A TD-ESI/MS/MS analysis is typically completed in less than 15 s, enabling high-throughput screening of a large number of samples [ 38 – 48 ]. Applications of TD-ESI/MS/MS in biomedicine include the detection of (1) semi-volatile chemical compounds such as ingested pesticides and drugs in biological fluids for emergency care [ 42 – 46 ], (2) active ingredients in pharmaceutical products [ 38 ], and (3) drugs in plasma for pharmacokinetic studies [ 47 , 48 ].…”

“…A TD-ESI/MS/MS analysis is typically completed in less than 15 s, enabling high-throughput screening of a large number of samples [ 38 – 48 ]. Applications of TD-ESI/MS/MS in biomedicine include the detection of (1) semi-volatile chemical compounds such as ingested pesticides and drugs in biological fluids for emergency care [ 42 – 46 ], (2) active ingredients in pharmaceutical products [ 38 ], and (3) drugs in plasma for pharmacokinetic studies [ 47 , 48 ]. In our previous study, TD-ESI/MS has been used to rapidly characterize sebaceous lipids [ 34 ].…”