Sensitive, High-Throughput Liquid Chromatography-Tandem Mass Spectrometry Analysis
of Atorvastatin and Its Pharmacologically Active Metabolites in Serum for Supporting
Precision Pharmacotherapy
(1336/2017) Támogató: Nemzeti Kutatás, Fejlesztés és Innovációs Iroda
The antihyerlipidemic drug atorvastatin (ATR) is used worldwide as part of the strategy
to prevent cardiovascular events. The high prevalence of patient nonadherence remains
an important challenge which could be addressed efficiently by precision pharmacotherapy
based on therapeutic drug monitoring (TDM). ATR is metabolized to pharmacologically
active metabolites, and evidence shows that the sums of ATR acid and lactone form
concentrations (ATR + ATRL), or of ATR and hydroxylated metabolites (ATR + MET) should
be assayed. A method is presented for the analysis of these substances in serum. Method
validation included the estimation of the quantitative relationship between the concentrations
and the standard deviations (SD), which supports the optimal incorporation of TDM
results into nonparametric pharmacokinetic models. The concentrations of the analytes
were evaluated in human subjects receiving ATR. The method's performance improved
by taking the sums of acid and lactone concentrations into account. The concentration-SD
relationship was linear, and we recommend applying Theil's regression for estimating
the assay error. All analytes could be detected by 2 h post dose in the samples of
human subjects. The changes in metabolite/parent drug concentration ratios in time
depended on the dose. The method is suitable for the TDM of ATR with a focus on precision
pharmacotherapy.