Simultaneous determination of a new dihydropyridine calcium antagonist (MPC-1304) and its metabolite in dog plasma by high-performance liquid chromatography with electrochemical detection

Determination of aranidipine and its active metabolite in human plasma by liquid chromatography/negative electrospray ionization tandem mass spectrometry

“…Methyl tert ‐butyl ether/cyclohexane (1:1) was found to yield the highest recovery for both AR and AR‐M with the best decontaminating effect of the plasma. A volume of 2 mL was found to be the proper volume for extraction, which was much less than that reported previously 5. Instead of using a large volume of buffer (0.5 mL)5 and 1 M NaOH,4 the pH was adjusted with 0.2 M Na 2 CO 3 and proved to increase the extraction recovery of the analyte, with concomitant lowering of the background interference.…”

“…Different LLE conditions were evaluated including different organic extraction solvents and buffers. Use of toluene5 and n‐hexane/diethyl ether (1:1)4 has been reported previously. To avoid using the toxic solvent toluene and the hazardous solvent diethyl ether, we tested ethyl ester, methyl tert ‐butyl ether, cyclohexane, methyl tert ‐butyl ether/cyclohexane (2:1, 1:1, 1:2).…”

“…The C max of AR in human plasma was reported to be below 1 ng · mL −1 when 5 mg AR was orally administrated to healthy volunteers 4. Current available data regarding the pharmacokinetics of AR and AR‐M was primarily acquired by a high‐performance liquid chromatography (HPLC) method with electrochemical detection (ECD)5 or a gas chromatography (GC)/negative‐ion chemical ionization mass spectrometric method 4. When the HPLC method combined with ECD was employed, it needed more time (30 min) to complete a sample analysis in order to avoid interfering endogenous substances in plasma, and the detection limit was as high as 0.25 ng · mL −1 , which could only fulfill the request for animal experiments, but was not sensitive enough for a human pharmacokinetic (PK) study.…”