Transl Clin Pharmacol.  2016 Mar;24(1):22-29. 10.12793/tcp.2016.24.1.22.

Development of a validated liquid chromatography-tandem mass spectrometry assay for the quantification of simvastatin acid, the active metabolite of simvastatin, in human plasma

• Park HJ
• Hwang AK
• Kim AR
• Kim SH
• Kim EH
• Cho SH
• Ghim JL
• Choe S
• Jung JA
• Jin SJ
• Bae KS
• Lim HS

• KMID: 2383596
• DOI: http://doi.org/10.12793/tcp.2016.24.1.22

Abstract

Simvastatin is a lipid-lowering drug that is metabolized to its active metabolite simvastatin acid (SA). We developed and validated a sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) method to quantitate SA in human plasma using a liquid-liquid extraction method with methanol. The protonated analytes generated in negative ion mode were monitored by multiple reaction monitoring. Using 500-mL plasma aliquots, SA was quantified in the range of 0.1-100 ng/mL. Calibration was performed by internal standardization with lovastatin acid, and regression curves were generated using a weighting factor of 1/χ2. The linearity, precision, and accuracy of this assay for each compound were validated using quality control samples consisting of mixtures of SA (0.1, 0.5, 5, and 50 ng/mL) and plasma. The intra-batch accuracy was 95.3-107.8%, precision was -2.2% to -3.7%, and linearity (r2) was over 0.998 in the standard calibration range. The chromatographic running time was 3.0 min. This method sensitively and reliably measured SA concentrations in human plasma and was successfully used in clinical pharmacokinetic studies of simvastatin in healthy Korean adult male volunteers.

Keyword

simvastatin acid; plasma; LC/MS/MS

MeSH Terms

Adult
Calibration
Humans*
Liquid-Liquid Extraction
Lovastatin
Male
Mass Spectrometry*
Methanol
Plasma*
Protons
Quality Control
Running
Simvastatin*
Volunteers
Lovastatin
Methanol
Protons
Simvastatin

Figure

• 

  Figure 1. Chemical structure of simvastatin acid (Source: http://pub-chem.ncbi.nlm.nih.gov/compound/64718#section=Top).

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  Figure 2. Full-scan product ion spectra of [M−H]+ for simvastatin acid and the lovastatin acid internal standard.

• 

  Figure 3. A typical calibration curve for simvastatin acid concentrations in human plasma.

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  Figure 4. Representative chromatograms of simvastatin acid in human plasma.

Reference

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