Lithium (Li) is used as a mood-stabilizing pharmaceutical drug and is widely prescribed for long-term maintenance treatment of bipolar disorder, with proven success in reducing both manic and depressive relapses, as well as diminishing suicidal tendencies. Li exhibits a narrow therapeutic window ranging from 0.5 to 1.2 mmol·L^-1 only, with higher levels potentially leading to toxic side effects¹. Accurate and regular monitoring of Li levels is therefore beneficial for patients, especially pregnant women as its improper use has been associated with risks for both mother and unborn child². In this context, a novel microfluidic microsampling device was developed at the KU Leuven Biosensors group enabling decentralized sample collection, hereby, facilitating therapeutic drug monitoring from home settings. The device allows automated separation of plasma from blood cells and collection on a pre-cut cellulose filter paper to form a volumetric dried plasma spot (DPS) without the need for any active components³. To date, the main analytical methods for lithium determination in DPS samples have relied on atomic absorption spectroscopy (AAS) or optical emission spectroscopy (OES).

In this work, a novel Laser Ablation Inductively Coupled Plasma Mass spectrometry (LA-ICP-MS) method was developed for the reliable and fast determination of Li after collection and drying of plasma on filter paper via the microsampling device. Validation was carried out by extraction of Li from DPS samples and subsequent solution ICP-MS analysis⁴. Upon an overnight acidic extraction of Li, recoveries for spiked plasma (centrifuged from whole blood) and certified plasma reference material ranged between 96 and 103%. A direct method for rapid determination of Li in the DPS themselves was developed relying on LA-ICP-MS and utilizing matrix-matched calibration standards. The addition of an internal standard (Co) onto the blank filter paper prior to the plasma spotting allowed to validate the method with a SeroNorm L-1 certified serum sample yielding recoveries of 90-110%. Although mapping the entire filter already reduced the analysis time compared to the liquid-based approach significantly, the quantification based on a random selection of 3, 5 or 7 radial lines across the filter further reduced the analysis time by 5-fold compared to the initial extraction-based method. This fast method may aim to be applied to actual spiked blood samples, potentially demonstrating the utility of both the DPS microsampling device and the subsequent Li quantification in DPS samples using LA-ICP-MS.

References

[1] R. Oruch; M.A. Elderbi; H. A. Khattab; I.F. Pryme; A, Lund. European journal of pharmacology, 2014, 740, 464-473.

[2] E.M. Poels; H. H. Bijma; M. Galbally; V. Bergink. International journal of bipolar disorders, 2018, 6(1), 26.

[3] D. Vloemans; L. Van Hileghem; W. Verbist; D. Thomas; F. Dal Dosso; J. Lammertyn. Lab on a Chip, 2021, 21(22), 4445-4454.

[4] S. Capiau; E. Bolea-Fernandez; L. Balcaen; C. Van Der Straeten; A.G. Verstraete; F. Vanhaecke; C.P. Stove. Talanta, 2020, 208, 120055.