Simple and validated UHPLC-MS/MS analysis of nimodipine in plasma and cerebrospinal fluid of patients with subarachnoid haemorrhage.
We present a simple, fast and validated method for the determination of nimodipine in plasma and cerebrospinal fluid (CSF) of patients with subarachnoid haemorrhage using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Plasma or CSF 250μL aliquots were pretreated with acetonitrile spiked with lacosamide as internal standard. The chromatographic separation was performed on a Fusion (3μm) 50×2.0mm I.D. column with gradient elution of 0.1% (v/v) formic acid in water and 0.1% (v/v) formic acid in acetonitrile at a flow rate of 0.35mL/min. The MS/MS ion transitions were 419.1→343 for nimodipine and 251.1→91 for the internal standard. The linearity was determined from 2.0 to 40.0ng/mL in plasma and 40.0-800.0pg/mL in CSF. The lower limit of quantitation (LLOQ) of nimodipine was 0.4ng/mL in plasma and 40pg/mL in CSF. The mean recovery for nimodipine was ≥75% in plasma and ≥90% in CSF at all three considered concentrations. Intra- and interassay precision and accuracy were ≤15% at all quality control concentrations in plasma and CSF. The method was applied to measure plasma and CSF concentrations of nimodipine in a series of patients with subarachnoid haemorrhage treated with intravenous nimodipine. The present procedure, omitting time-consuming liquid-liquid extraction and drying steps, is faster, simpler and cheaper than published LC-MS/MS analytical methods for nimodipine in plasma and the first validated one for nimodipine in CSF.
IRCCS-ISNB Institute of Neurological Sciences of Bologna, Bologna, Italy.
Susan
S
Mohamed
IRCCS-ISNB Institute of Neurological Sciences of Bologna, Bologna, Italy; Department of Biomedical and Neuromotor Sciences University of Bologna, Bologna, Italy.
Roberto
R
Riva
IRCCS-ISNB Institute of Neurological Sciences of Bologna, Bologna, Italy; Department of Biomedical and Neuromotor Sciences University of Bologna, Bologna, Italy. Electronic address: manuela.contin@unibo.it.
Manuela
M
Contin
D002121:Calcium Channel Blockers / Q000097:blood* / Q000134:cerebrospinal fluid*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D057230:Limit of Detection; D009553:Nimodipine / Q000097:blood* / Q000134:cerebrospinal fluid*; D013345:Subarachnoid Hemorrhage / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy; D053719:Tandem Mass Spectrometry / Q000379:methods*
D002121:Calcium Channel Blockers; D009553:Nimodipine
CSF concentration; Nimodipine; Plasma concentration; Subarachnoid haemorrhage; Ultra high performance liquid chromatography tandem mass spectrometry