Development and validation of a high throughput and robust LC–MS/MS with electrospray ionization method for simultaneous quantitation of diltiazem and its two metabolites in human plasma: Application to a bioequivalence study

Investigation of diltiazem metabolism in fish using a hybrid quadrupole/orbital trap mass spectrometer

“…This corresponds to a chromatographic gradient as presented in Supplementary Table S1 (see Supporting Information). A list of all prospective metabolites of diltiazem was prepared for further investigation based on the literature and general principles of drug metabolism in different living tissues . Generally, the products of different drug biotransformations and decomposition are assumed to be more hydrophilic, so they should elute before the parent compound.…”

“…Most studies focused on diltiazem metabolites have generally dealt with mammalian and human tissues. Recent studies have presented analytical methods for only a limited number of diltiazem metabolites ( N ‐desmethyl diltiazem and desacetyl diltiazem) . To the best of our knowledge, only one study has described a method for determining 11 phase I metabolites of diltiazem in human plasma …”

“…In mammals, diltiazem metabolism is well documented. [11][12][13][14][15][16][17][18] In humans, it is metabolized into three major products, O-desacetyl diltiazem, N-desmethyl diltiazem, and Ndesmethyl-O-desacethyl diltiazem, [19,20] which are all found in blood plasma. O-Desacethyl and N,O-didesmethyl diltiazem are pharmacologically active and their effects differ from the parent compound.…”

Emerging Analytical Separation Techniques with High Throughput Potential for Pharmaceutical Analysis, Part I: Stationary Phase and Instrumental Developments in LC

“…No reference to a guideline was given in [27,45,43,50,52,54,56,58]. The ICH guideline [59] was followed in [5,9,33,34,36,40] and the FDA guideline [60] in [51,53].…”

“…Due to its vast potential in this area, the number of papers on UPLC in bio-analysis has continued expanding from 2006 until now. Many papers have proved the excellent and rapid separation performance of UPLC for drugs and their metabolites in bio-fluids [5,27,[51][52][53][54][55][56][57][58]. Novakova et al [9] developed a fast UPLC method to assay simultaneously simvastatin and atorvastatin with their relative metabolites and related substances in clinical samples.…”