Determination of Nimodipine in Human Plasma by HPLC-ESI-MS and Its Application to a Bioequivalence Study

Abstract

A simple, specific, and precise liquid chromatographic-electrospray ionization mass spectrometric (LC-ESI-MS) method has been developed for determination of nimodipine concentration in human plasma. The method involves the addition of 200 microL of saturated sodium bicarbonate (NaHCO(3)) solution to plasma to improve the extraction recovery, liquid-liquid extraction of nimodipine from plasma samples with anhydrous diethyl ether, simple reversed-phase chromatography, and ESI mass spectrometric detection in negative ion selected ion monitoring mode (SIM) using target [M-] ions at m/z 417 and m/z 359 for nimodipine and nitrendipine (internal standard, IS), respectively. A complete analytical run was achieved within 3.5 min. The limit of quantification was 0.5 ng/mL. The method was validated within a linear range of 0.5-100 ng/mL. The correlation coefficient for the calibration regression line was 0.9995 or better. Intra- and inter-batch accuracy and precision were acceptable. Analyte was stable in a battery of stability studies. The method has been successfully used in a bioequivalence study.

Simple and validated UHPLC–MS/MS analysis of nimodipine in plasma and cerebrospinal fluid of patients with subarachnoid haemorrhage

“…Calculated mean plasma concentrations of NIM were within ±15% of the nominal concentrations for both LLOQ and high QCs in all the experimental conditions, in line with previously reported data [9][10][11][12][13]. From previous literature, stored plasma samples at < −50 • C proved stable for NIM up to 21 days (10).…”

“…Moreover, compared with the HPLC-MS/MS methods reported so far for the quantitation of NIM in human plasma [9][10][11][12][13], this assay presents two main advantages: it significantly simplifies sample pretreatment, by omitting timeconsuming LLE, avoiding multiple-step sample pretreatment, thus reducing the risks of analytical errors; it employs lower plasma volumes (250 L vs 0.3-1 mL) with comparable LLOQ (0.4 ng/mL vs 0.1-0.5 ng/mL). The method's quantitation range for NIM in both plasma and CSF is adequate for therapeutic drug monitoring in SAH patients at recommended oral and parenteral drug dosages [7,8].…”

“…It has been suggested that the neuroprotective effect of NIM might be higher after parenteral administration, possibly due to matched higher plasma and cerebrospinal fluid (CSF) drug concentrations [3], but therapeutic plasma concentrations of NIM are not yet defined. Several methods have been published for quantitation of NIM in human plasma, based on HPLC-MS/MS coupled with laborious sample liquid-liquid extraction [9][10][11][12][13]. To our knowledge, no validated method has been reported so far for the analysis of NIM in human CSF.…”

Folate-targeted star-shaped cationic copolymer co-delivering docetaxel and MMP-9 siRNA for nasopharyngeal carcinoma therapy

“…In vivo target experiment, for DOC distribution analysis, compared to liquid–liquid anhydrous diethyl ether extraction method [28], we found tissue sample extracted by low toxicity tert-butyl methyl ether can be blown dry easily by nitrogen, and the higher DOC extraction rate in tissue was acquired [24]. Because of the two compartment model of drug distribution, after tail intravenous injection, nanomedicines were distributed immediately in central compartment of organs with abundant blood supply such as liver, heart, kidney and so on, concentration of DOC dropped fastly following with accelerated blood flow, and then nanomedicines were distributed slowly in peripheral compartment of organs with less blood flow such as skin, fat, bone and so on, and GFP expression in vivo was similar to DOC distribution.…”

CD-PLLD co-delivering docetaxel and MMP-9 siRNA plasmid for nasopharyngeal carcinoma therapy in vivo

“…The present study investigated the in vivo applications for NPC therapy. Using a DOC distribution analysis, compared with the liquid-liquid anhydrous diethyl ether extraction method (25), it was demonstrated that tissue samples extracted by low-toxicity tert-butyl methyl ether are easily dried by nitrogen, acquiring an increased DOC extraction rate (26). Due to its size, the nanomedicine is easily delivered to the tumor cell, and accumulates in tumor tissues for enhanced permeability and retention (27,28).…”