Therapeutic monitoring of serum digoxin for patients with heart failure using a rapid LC-MS/MS method

The Role of Cardiotonic Steroids in the Pathogenesis of Cardiomyopathy in Chronic Kidney Disease

“…The effects of high Ca 2+ on contractility [42] and induction of hypertrophic signalling cascades in the heart are well known [43]. However, when concentrations of CTS detected in serum of experimental animals and patients were shown to be in the range of 0.5-20 n M [16,17,18,19,20,21,22,23,24,25,26,27,28], these were considered too low to modulate the activity of the NKA and thus were not expected to affect intracellular Na + and Ca 2+ concentrations [44]. Therefore, in addition to its transport function, a hypothesis that the NKA also acts as a receptor for the CTS has been presented.…”

“…Nanomolar concentrations of CTS, such as ouabain, digoxin, marinobufagenin, bufalin and telocinobufagin, are detected in serum of experimental animals and humans [16,17,18,19,20,21,22,23,24,25,26,27,28]. CTS can be divided into two structurally distinct groups, cardenolides and bufadienolides.…”

A sensitive method for digoxin determination using formate-adduct ion based on the effect of ionization enhancement in liquid chromatograph–mass spectrometer

“…The method developed here has an injection volume of 5 L (using a column of 100 mm × 2.1 mm, 5 m), well within the suggested limit, which allows analysis of trace amounts of sample and improves column performance in the LC/MS/MS procedure. Additionally, unlike previously described methods that use gradient elution [2,[5][6][7][8][9][10][11][12][13], which leads to a higher column pressure and compromises HPLC analysis, our method does not use gradient elution. Other advantages include a short analysis time, a simple mobile phase and sample extraction procedure, and the used of Oasis HLB Elution plates in the final optimized method, which can determine digoxin from only 100 L of biological sample (rat plasma).…”

“…To our knowledge, the most commonly used formic acid concentration used for digoxin determination is 0.1% (v/v) which is likely to be at the lower end on the concentration range [2,[5][6][7][8][9][10][11][12][13]. After the [M+HCOO] − adduct was chosen for subsequent investigation, a mobile phase consisting of 0.1% acetonitrile:formic acid (60:40, v/v) resulted in a relatively low ion intensity that was comparable to the [M+NH 4 ] + ion.…”

“…LC/MS/MS is a highly efficient analytical tool for biological and nonbiological analysis. Some LC/MS/MS methods for quantifying digoxin have been reported, but in this study we developed a novel rapid and sensitive approach using formate-adduct ions [M+HCOO] − , found in Q1 scanning exhibited higher response than any other fragment ions [2,[5][6][7][8][9][10][11][12][13]. Formate-adducts afforded a limit of quantitation (LOQ) of 0.2 ng/mL and an amount on column (AOC) of 0.001 ng, which are both lower than most previously reported methods (Table 1).…”