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. 2022 Mar 19;12(1):4757.
doi: 10.1038/s41598-022-08804-x.

Detection and characterization of simvastatin and its metabolites in rat tissues and biological fluids using MALDI high resolution mass spectrometry approach

Wencui Yin  1 , Reem I Al-Wabli  1 , Mohamed W Attwa  1 , A F M Motiur Rahman  2 , Adnan A Kadi  3
Affiliations

Detection and characterization of simvastatin and its metabolites in rat tissues and biological fluids using MALDI high resolution mass spectrometry approach

Wencui Yin et al. Sci Rep. .

Abstract

Simvastatin (SV) is a hypolipidemic agent, and it is the 2nd most widely prescribed lipid-lowering drug. Here, the detection and characterization of SV and its metabolites was studied in selected organs/tissues (lung, liver, brain, heart and kidney) and biological samples (blood, urine and feces) of rats. MALDI Orbitrap MS was used as a high-resolution mass analyzer. 2,5-Dihydroxybenzoic acid (DHB) and 1,5-diaminonaphthalene (DAN) were used as matrices. Several sample loading methods onto the MALDI plate were attempted and dried droplet method was found to be superior. Two different cell disruption methods, pulverization and homogenization, were also evaluated for the optimum sensitivity in MALDI. Pulverization allowed the detection of more metabolites in all organs except the liver, where homogenization led to the detection of more metabolites. Altogether, 13 metabolites were detected, and one metabolite tentatively identified as a reduced product is being reported for the first time. SV and its metabolites were distributed to all the tissues studied except the brain. Overall, the results implied that the pulverized samples were more uniform and larger in surface area, resulting in their more efficient and complete extraction during sample preparation. As shown in the present study, MALDI Orbitrap MS is a useful tool to study drug and metabolite detection and characterization.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Chemical structures of some known statins.
Figure 2
Figure 2
The in vivo metabolism of SV.
Figure 3
Figure 3
High-resolution mass spectrum of hydroxy-SV (M2) obtained using an Orbitrap MS showing possible hydroxylation sites of SV (A) and exact and accurate mass values (B).
Figure 4
Figure 4
High-resolution mass spectrum of SVA (M8) obtained using an Orbitrap MS showing the possible hydrolysis of SV (A) and exact and accurate mass values (B).
Figure 5
Figure 5
High-resolution mass spectrum of reduced-SV (M5) obtained using an Orbitrap MS showing the possible reduction of SV (A) and exact and accurate mass values (B).
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