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

Mohamed, Susan; Riva, R.; Contin, Manuela

doi:10.1016/j.jchromb.2016.06.012

Cited by 7 publications

(5 citation statements)

References 19 publications

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“…Calle et al, measured 31–42 ng/mL in plasma, 12 hours after 4 mg/mL [29], which parallels a human study where clinically relevant intravenous (i.v.) injections of 2.0 mg/hour gave a steady-state nimodipine concentration of 27.1–34.0 ng/mL [32]. 2.5 mg/kg s.c. nimodipine has been shown to be better than oral treatment of SAH in rabbits, and we chose this experimental approach [30].…”

Section: Methodsmentioning

confidence: 99%

MEK1/2 inhibitor U0126, but not nimodipine, reduces upregulation of cerebrovascular contractile receptors after subarachnoid haemorrhage in rats

et al. 2019

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Vascular pathophysiological changes after haemorrhagic stroke, such as phenotypic modulation of the cerebral arteries and cerebral vasospasms, are associated with delayed cerebral ischemia (DCI) and poor outcome. The only currently approved drug treatment shown to reduce the risk of DCI and improve neurologic outcome after aneurysmal subarachnoid haemorrhage (SAH) is nimodipine, a dihydropyridine L-type voltage-gated Ca 2+ channel blocker. MEK1/2 mediated transcriptional upregulation of contractile receptors, including endothelin-1 (ET-1) receptors, has previously been shown to be a factor in the pathology of SAH. The aim of the study was to compare intrathecal and subcutaneous treatment regimens of nimodipine and intrathecal treatment regimens of U0126, a MEK1/2 inhibitor, in a single injection experimental rat SAH model with post 48 h endpoints consisting of wire myography of cerebral arteries, flow cytometry of cerebral arterial tissue and behavioural evaluation. Following ET-1 concentration-response curves, U0126 exposed arteries had a significantly lower ET-1 max than vehicle arteries. Arteries from both the intrathecal- and subcutaneous nimodipine treated animals had significantly higher ET-1 max contractions than the U0126 arteries. Furthermore, Ca 2+ concentration response curves (precontracted with ET-1 and in the presence of nimodipine) showed that nimodipine treatment could result in larger nimodipine insensitive contractions compared to U0126. Flow cytometry showed decreased protein expression of the ET B receptor in U0126 treated cerebral vascular smooth muscle cells compared to vehicle. Only U0126 treatment lowered ET-1 max contractions and ET B receptor levels, as well as decreased the contractions involving nimodipine-insensitive Ca 2+ channels, when compared to both intrathecal and subcutaneous nimodipine treatment. This indicate that targeting gene expression might be a better strategy than blocking specific receptors or ion channels in future treatments of SAH.

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Section: Methodsmentioning

confidence: 99%

MEK1/2 inhibitor U0126, but not nimodipine, reduces upregulation of cerebrovascular contractile receptors after subarachnoid haemorrhage in rats

et al. 2019

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“…Indeed, the concentration of Np in the cerebrospinal fluid (CSF) is one order of magnitude lower than that in the plasma, either by intravenous drip or oral administration. [ 8 ] However, in order to cure TBI, a high dosage of Np is needed around the TBI wound cavity. Unfortunately, increasing the dose of Np may cause hypotension; [ 9 ] thus, currently, the side effects of Np for TBI treatment may outweigh the benefits.…”

Section: Introductionmentioning

confidence: 99%

A Novel Targeted Nanoparticle for Traumatic Brain Injury Treatment: Combined Effect of ROS Depletion and Calcium Overload Inhibition

Han

Huang

et al. 2022

Adv Healthcare Materials

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Survival after severe traumatic brain injury (TBI) depends on minimizing or avoiding secondary insults to the brain. Overproduction of reactive oxygen species (ROS) and Ca2+ influx at the damaged site are the key factors that cause secondary injury upon TBI. Herein, a TBI‐targeted lipid covered radical scavenger nanoparticle is developed to deliver nimodipine (Np) (CL‐PPS/Np), in order to inhibit Ca2+ influx in neurons by Np and to scavenge ROS in the brain trauma microenvironment by poly(propylene sulfide)60 (PPS60) and thus prevent TBI‐associated secondary injury. In post‐TBI models, CL‐PPS/Np effectively accumulates into the wound cavity and prolongs the time of systemic circulation of Np. CL‐PPS/Np can markedly protect the integrity of blood‐brain barrier, prevent brain edema, reduce cell death and inflammatory responses, and promote functional recovery after TBI. These findings may provide a new therapy for TBI to prevent the spread of the secondary injury.

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“…It is crucial to incorporate stereochemistry knowledge into the growing range of laboratory analytical methods and it is extremely important to emphasize the use of enantioselective assays when determining the effectiveness and adverse effect profiles or studying the disposition of chiral therapeutic agents. Several analytical procedures have been reported to determine nimodipine concentrations in biological samples utilizing various techniques, including gas chromatography, high‐performance liquid chromatography and liquid chromatography tandem mass spectrometry (LC–MS/MS) (do Nascimento et al, 2010; Fischer et al, 1993; Krol, Noe, Yeh, & Raemsch, 1984; Mohamed, Riva, & Contin, 2016; Muck, 1995; Qin et al, 2008; Wanner‐Olsen et al, 2000; Zhao et al, 2010). However, the majority of the methods in the literature were nonenantioselective.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Enantioselective assay of nimodipine in human plasma using liquid chromatography–tandem mass spectrometry

Isse

Mahmoud

2020

Biomedical Chromatography

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Nimodipine is a dihydropyridine calcium channel blocker that exhibits higher selectivity toward cerebral blood vessels compared with other members of the same class. It has been shown to improve outcomes and prevent delayed cerebral ischemia in the setting of aneurysmal subarachnoid hemorrhage, a life‐threatening brain bleed. Nimodipine is a chiral compound and it is marketed as a racemic mixture of (+)‐R and (−)‐S enantiomers. (−)‐S‐Nimodipine is approximately twice as potent a vasorelaxant as the racemic mixture and is more rapidly eliminated than the (+)‐R counterpart following oral dosing. Few analytical procedures have been reported to determine nimodipine enantiomers in biological samples; however, the reported methods were time‐consuming, involved multistep extraction procedures and required large sample volumes. Herein, we present an LC–MS/MS method for quantifying nimodipine enantiomers in human plasma using a small sample volume (0.3 ml) and a single liquid–liquid extraction step. The peak area ratios were linear over the tested concentration ranges (1.5–75 ng/ml) with r2 > 0.99. The intraday CV and percentage error were within ±14% while the interday values were within ±13%, making this analytical method feasible for research purposes and pharmacokinetic studies.

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

Cited by 7 publications

References 19 publications

MEK1/2 inhibitor U0126, but not nimodipine, reduces upregulation of cerebrovascular contractile receptors after subarachnoid haemorrhage in rats

MEK1/2 inhibitor U0126, but not nimodipine, reduces upregulation of cerebrovascular contractile receptors after subarachnoid haemorrhage in rats

A Novel Targeted Nanoparticle for Traumatic Brain Injury Treatment: Combined Effect of ROS Depletion and Calcium Overload Inhibition

Enantioselective assay of nimodipine in human plasma using liquid chromatography–tandem mass spectrometry

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