A rapid chromatographic/mass spectrometric method for digoxin quantification in human plasma

Abstract

The relatively simple liquid-liquid extraction LC-MS/MS method using a UPLC column for measurement of digoxin concentrations both in medium and human plasma is described. Digitoxin was used as internal standard. The developed method possesses satisfactory accuracy, precision, and repeatability, and is economical and not time-consuming. It is the first method for precise measurement of digoxin concentrations in human plasma using combined HPLC equipment and UPLC column with a low limit of quantitation equal to 0.1 ng ml -1 as verified in more than 1500 samples analyzed in a GCP GLP bioequivalence study. The developed method was successfully used in digoxin bioequivalence studies in which 26 volunteers were enrolled.

Simultaneous quantification of digoxin, digitoxin, and their metabolites in serum using high performance liquid chromatography‐tandem mass spectrometry

“…Additionally, the method was also directed at semi-quantitative analysis of deslanoside and lanatoside. Several individual liquid chromatography-mass spectrometry (LC-MS) assays for digoxin and digitoxin [20][21][22][23][24][25][26][27][28][29][30] have been reported as well as in combination with their metabolites or related cardiac glycosides. [19,[31][32][33][34][35] To our knowledge, no LC-MS/MS method has been described for simultaneous quantification of the above combination of drugs and their metabolites.…”

An automated streamlined method for the therapeutic drug monitoring of digoxin based on the online‐solid‐phase extraction liquid chromatography tandem high‐resolution mass spectrometry

“…The generated ions of digoxin include the positive ions 8,11,13,15 [M + Li] +9 and the negative ions [M-H] À , [M + HCOO] -, 14 [M + CF 3 COO] -. 6 However, the full MS-SIM indicated that the presence of the formic acid gave rise to formate-adduct ions [M + HCOO] À as the predominant ion for digoxin, with an m/z value of 825.42781. The formation of the formate-adduct ions resulted in a very simple mass spectra for digoxin.…”

“…In the past decade, determination of digoxin in biological specimens was primarily accomplished using liquid chromatography tandem mass spectrometry (LC-MS, LC-MS/MS) 4,[6][7][8][9][10][11][12][13][14][15] and surfaceassisted laser desorption/ionization mass spectrometric detection (SALDI/MS). 16 MS/MS offered considerable advantages, including speed, selectivity, sensitivity, and robustness, and was a highly efficient analytical tool for biological specimens.…”

“…17 Recent developments in high-resolution mass spectrometry (HRMS) had resulted in quantitation abilities comparable to those of MS/MS, besides its high resolving power, high mass accuracy, and highperformance quadrupole for selectivity. 18,19 Sample pretreatment methods prior to the analytical procedure were similar across methods, such as liquid-liquid extraction (LLE), [6][7][8] protein precipitation (PP), 4,9,12,15 and solid-phase extraction (SPE) 10,11,13,14 as well as dispersive liquid-liquid microextraction. 16 These traditional techniques are time-consuming and labor-intensive especially for a large number of samples.…”

Development and Validation of a UHPLC-ESI-MS/MS Method for Quantification of Oleandrin and Other Cardiac Glycosides and Evaluation of Their Levels in Herbs and Spices from the Belgian Market

“…A number of analytical, mostly single-analyte, methods for quantification of CGs in biological matrices have been described [11,[17][18][19][20][21][22][23][24]. As a detection technique, these methods utilized mass spectrometry (MS) coupled to liquid chromatography (LC), which, thanks to its good selectivity and sensitivity, has nowadays become the method of choice for many applications including toxin analysis.…”