Determination of nimodipine in plasma by HPLC-MS/MS and pharmacokinetic application

Abstract

To develop and validate a rapid, specific and highly sensitive method to quantify nimodipine in human plasma using dibucaine as the internal standard (IS). The analyte and IS were extracted from plasma samples by liquid-liquid extraction using hexane-ethyl acetate (1:1 v/v). The chromatographic separation was performed on a Varian ® Polaris C18 analytical column (3 mm, 50 x 2.0 mm) and pre-column Securityguard TM C18 (4.0 x 3.0 mm) with a mobile phase of Acetonitrile-Ammonium acetate 0.02 ml/L (80:20v/v). The method had a chromatographic run time of 4.5 min and linear calibration curve over the range of 0.1-40 ng/mL (r > 0.9938). The limit of quantification was 100 pg/mL. Acceptable precision and accuracy were obtained for concentrations over the standard curve ranges. This validated method was successfully applied in determining the pharmacokinetic profile of nimodipine tablets of 30 mg administered to 24 healthy volunteers. The proposed method of analysis provided a sensitive and specific assay for nimodipine determination in human plasma. The time for the determination of one plasma sample was 4.5 min. This method is suitable for the analysis of nimodipine in human plasma samples collected for pharmacokinetic, bioavailability or bioequivalence studies in humans.Uniterms: Nimodipine/determination in plasma. Nimodipine/pharmacokinetic profile. Nimodipine/ quantitative analysis. Pharmacokinetics/method validation.Um método rápido, específico e sensível para quantificar nimodipino em plasma humano usando dibucaína como padrão interno (IS) é descrito. O analito e o IS foram extraídos das amostras de plasma por extração líquido-líquido usando hexano-acetato de etila (1:1 v/v). A separação cromatográfica foi realizada utilizando-se uma coluna analítica C18 Varian ® Polaris (3 mm, 50 x 2,0 mm) e uma pré-coluna Securityguard TM C18 (4,0 x 3,0 mm) e acetonitrila-acetato de amônia 0,02 mol/L (80:20 v/v) como fase móvel. O método apresentou tempo total de corrida de 4,5 min e curva de calibração linear com concentrações entre 0,1-40 ng/mL (r > 0,9938). O limite de quantificação foi de 100 pg/mL. Os valores de precisão e exatidão foram obtidos por meio da análise das amostras de controle de qualidade. A análise de uma única amostra de plasma foi realizada em 4,5 minutos. A metodologia validada foi aplicada na determinação do perfil farmacocinético do nimodipino, comprimido de 30 mg administrado em 24 voluntários saudáveis. O método para quantificar nimodipino em plasma é adequado para aplicação em estudos farmacocinéticos, biodisponibilidade e bioequivalência em humanos.

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.…”

Solid dispersion systems engineered from hydroxypropyl‐β‐cyclodextrin and water‐soluble polymers for enhanced oral bioavailability of nimodipine

“…The drug content of NMD in the SD rat plasma was assayed using HPLC methodology 32 . The HPLC system comprises a model LC‐10AT pump (Shimadzu, Kyoto, Japan), SPD‐10A programmable photodiode array detector (Shimadzu, Kyoto, Japan), and Waters Atlantis dC18 (4.6 × 150 mm) was used in the analysis.…”

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

“…Over the years, several analytical methods have been published for the quantification of NMD in biological matrices, including HPLC , LC‐MS , LC‐MS/MS , and UHPLC‐MS/MS . However, due to the low polarity of NMD, conventional RPLC for the quantification of NMD requires a long analysis time.…”