Development and optimization of a supercritical fluid chromatography tandem mass spectrometry method for the high‐throughput determination of nimodipine in beagle plasma

Abstract

A simple, sensitive, and efficient supercritical fluid chromatography with tandem mass spectrometry method was established for the determination of nimodipine in beagle plasma. One‐step protein precipitation with acetone was used to extract the analytes from the plasma. Nitrendipine was used as the internal standard. The chromatographic separation was achieved on an ACQUITY UPC2™ BEH 2‐EP column, and a gradient elution program was applied at a flow rate of 1.5 mL/min. The detection was carried out on a triple quadrupole tandem mass spectrometer with an electrospray ionization source operating in positive ion mode. Quantification was performed using multiple reaction monitoring of the transitions of m/z 419.3→301.3 for nimodipine and m/z 361.4→315.2 for nitrendipine. A satisfactory linearity was obtained over the concentration range of 0.5–800 ng/mL (r > 0.996). The intra‐ and interday precision and accuracy results were <9.1% across the quality control levels. The peak concentration and area under concentration‐time curve (0–720 min) values of the test and reference formulations were 279.28 ± 211.46 and 265.13 ± 149.26 ng/mL, 25608.00 ± 17553.65 and 28553.67 ± 20207.92 ng·min/mL, respectively. The validated method was successfully applied to reveal the pharmacokinetic profiles of nimodipine in beagle dogs after oral administration. Moreover, the analytical method could be used for further bioequivalence studies.

QuEChERS-Based Approach to the Extraction of Five Calcium Channel Blockers from Plasma Determined by UPLC-MS/MS

“…The developed method has LOD and LOQ of 0.014, 0.048 for AML, and 0.007,0.025 for NIM. Existing studies have shown LOD and LOQ greater than 0.2 and 0.5 for AML [ 11 , 12 ] and greater than 0.05 and 0.12 for NIM [ 13 , 14 ]. The new method demonstrated lower LOD and LOQ and, therefore, has higher sensitivity than published methods.…”

“…Liquid chromatography-mass spectrometry (LC-MS) approaches are among the most widely applied strategies for the detection of a diverse range of compounds, and they are the primary strategy employed to analyze calcium antagonists in bio-samples including serum, plasma, and milk owing to their excellent sensitivity and acquisition speed [ 10 , 11 , 12 , 13 , 14 ]. The combination of high-performance liquid chromatography and ultraviolet detection (HPLC-UV) [ 11 ], gas chromatography-tandem mass spectrometry (GC-MS) [ 15 ], and GC with electron-capture detection (GC-ECD) have also been used in various research settings. However, LC-based strategies alone cannot provide sufficient sensitivity when detecting many compounds, given that samples containing complex substrates inevitably contain many spurious peaks for which effective separation cannot be achieved.…”

“…Appropriate analytical sample preparation is essential to mitigate interference caused by endogenous compounds or drug metabolites when biological samples consist of a complex matrix likely to disturb analyses. To date, many extraction techniques have been designed including protein precipitation (PP) [ 12 ], liquid-liquid extraction (LLE) [ 14 ], solid-phase extraction (SPE) [ 11 , 13 ], solid-phase microextraction (SPME), and others have been developed and used to measure drug concentrations in blood samples. However, these techniques are subject to certain limitations including high costs and complex workflow techniques.…”

Analytical Methods of Some Calcium Channel Blockers. A Brief Review.

“…The injector and detector were both 250°C, and the carrier gas was nitrogen (Xiang, Zhang et al 2014). To determine NIM in beagle plasma, a supercritical fluid chromatography tandem mass spectrometry technique was applied (Wang, Li et al 2019). A supercritical fluid chromatography-ESI-MS/MS technique had been developed to identify NIM and 3n-butylphthalide in the plasma of beagles.…”

Matrix effect in bioanalytical assay development using supercritical fluid chromatography‐mass spectrometry

“…Whereas ME in LC–MS has been extensively investigated and discussed (Matuszewski et al, 2003; Van Eeckhaut et al, 2009; Zhou et al, 2017), ME in SFC‐MS bioanalytical method development has not been systematically reviewed. As the use of SFC‐MS in the analysis of biological samples has increased, ME in SFC‐MS has also been investigated (Losacco et al, 2020; Wang, Li, et al, 2019) and reports have focused on the comparable analysis between the ME in SFC‐MS and other chromatographic techniques for achiral separation of biological samples (Svan et al, 2018; Wolrab et al, 2020).…”