Rapid analysis of metabolic stability of dopamine receptor antagonists and detection of their metabolites by liquid chromatography/tandem mass spectrometry

High-performance liquid chromatography–tandem mass spectrometry in the identification and determination of phase I and phase II drug metabolites

“…In general, low-resolution mass analyzers (e.g., quadrupoles and ion traps) have resolution in the low-thousands range, while high-resolution analyzers should provide a minimum resolution of 15,000 for time of flight (TOF) based analyzers [ 42 , 71 , 101 ] or over 50,000 for Fourier transform mass analyzers [ 102 – 104 ]. The advantage of ion traps (both spherical and linear) is the possibility of MS n scan, which is useful for studying fragmentation paths [ 49 , 105 – 108 ], as illustrated for the example of the fragmentation pattern determined on the basis of MS n spectra (Fig. 3 ).…”

“…In the case of nitrogen, there is often double alkyl substitution; hence, two deakylations are necessary to uncover the amino group. When the demethylation occurs, new hydroxyl [ 19 , 25 , 40 , 46 , 108 , 129 – 131 ] or thiol [ 132 ] groups can undergo fragmentation in MS/MS mode, yielding the typical neutral losses of H 2 O or H 2 S, respectively. In the case of the amino group formed by N-demethylation [ 133 ], the neutral loss of NH 3 is not common.…”

“…The oxidation is, in general, the introduction of an oxygen atom by various reactions, such as hydroxylation (one or multiple times) [ 23 , 24 , 40 , 45 , 47 , 51 , 52 , 76 , 83 , 102 , 108 , 112 , 124 , 130 , 131 , 135 – 139 ] and aliphatic and aromatic epoxidation [ 77 , 124 , 140 , 141 ], which is often followed by hydrolysis leading to dihydrodiol formation [ 141 ]. Epoxides have the same elemental composition as hydroxylated metabolites and similar retention behavior, so their differentiation depends on the interpretation of their mass spectra and UV spectra for aromatic epoxides.…”

PANI: Ni(Leu)2 based non-enzymatic electrochemical dopamine sensor

“…It is crucial to precisely determine the amount of the active component in DOP-based pharmaceuticals as well as the concentration of DOP in biological fluids. Optically based assays [6], liquid chromatography [7], electrophoresis [8], electrochemical sensors [9], optical-electrochemical sensors [10], and other strategies have all been developed over the past few decades for the measurement of DOP levels. Due to their low cost, lightweight equipment, rapid response, high specificity range, high sensitivity, excellent selectivity, and low limit of detection, electrochemical sensors are regarded as the more attractive and potentially useful sensor technology among them.…”

Collection of selected reaction monitoring and full scan data on a time scale suitable for target compound quantitative analysis by liquid chromatography/tandem mass spectrometry

“…Previous work by Cai and coworkers demonstrated the utility of acquiring full scan data and quantitative data from the same sample set; they were able to detect both unknown metabolites and target compounds in plasma from in vivo PK experiments and in liver S9 5,6. Lee and coworkers described a similar approach with the QITMS applied to metabolic stability of dopamine receptor antagonists 7. Similar advantages with the acquisition of full scan data at the time of quantitation were also demonstrated by Zhang et al .…”