Article
Determination of nimodipine concentrations in plasma and cerebrospinal fluid of patients following aneurysmal subarachnoid hemorrhage
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Authors
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Sonani Mindt
- Universitätsklinikum Mannheim, Chemie, Mannheim, Deutschland
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Ursala Tohki
- Universitätsklinikum Mannheim, Neurochirurgische Klinik, Mannheim, Deutschland
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Hugo Andrade-Barazarte
- Universitätsklinikum Mannheim, Neuroradiologie, Mannheim, Deutschland
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Michael Neumaier
- Universitätsklinikum Mannheim, Chemie, Mannheim, Deutschland
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Daniel Hänggi
- Universitätsklinikum Mannheim, Neurochirurgische Klinik, Mannheim, Deutschland
| Published: | June 18, 2018 |
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Outline
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Objective: Delayed cerebral ischemia (DCI) is an important cause of morbidity after aneurysmal subarachnoid hemorrhage (aSAH). Its time of appearance is uncertain, and its complications are devastating affecting patients’ outcome. Nimodipine is the only drug approved by the FDA for improving outcome after SAH. Clinically, however, there are no specific values of this drug in plasma or cerebrospinal fluid (CSF) during aSAH treatment that could be associated with outcome improvement. Our aim was to establish a method to measure nimodipine concentrations in plasma and CSF of patients after aSAH, and to determine the therapeutic concentrations of this drug associated with clinical response.
Methods: From June 2017 to November 2017, we prospectively collected clinical data of patients with aSAH admitted to our neurosurgical department. All the included patients received nimodipine orally, and followed a standard dose of 60 mg every 4 hours. Patients, who developed clinical vasospasm during their in-hospital stay, underwent intra-arterial application of nimodipine (800 ng/ml), followed by angiographic control. In order to determine nimodipine concentrations, we established a method using the high performance liquid chromatography (LC) coupled with mass spectrometric (MS) analysis (LC/MS) for further quantification of nimodipine concentrations in serum and in CSF.
Results: Our LC/MS method allowed quantification of nimodipine concentrations in plasma with lower limit of quantification (LOQ) of 0.2 ng/ml, and with an LOQ of 0.15 ng/ml in CSF respectively. The MS/MS ion transitions were 419.2/343.0 for nimodipine and 247.0/ 98.0 for the internal standard. Nimodipine concentrations in CSF were significantly lower (1.0 ± 1.3 ng/ml) than plasma concentrations (15.1 ± 24.7 ng/ml) concentrations. After intra-arterial nimodipine boluses for treatment of vasospasms, serum and CSF nimodipine concentrations were slightly higher than patients who received only oral nimodipine.
Conclusion: The LC/MS analysis allows identification and measurement of nimodipine concentrations in plasma and CSF of patients after aSAH. The initial stage of this study provided the first concentrations values of nimodipine in plasma and CSF. Furthermore, we demonstrated that intra-arterial boluses of nimodipine had led to higher concentrations in plasma and CSF, when compared to the oral application.
