Objective: To study the compatibility stability and pharmacokinetics of nimodipine concentration for injection in Beagle dogs. Methods: A Hyper Star BDS C18 column (150 mm×4.6 mm, 5 μm) was used; the mobile phase was water-tetrahydrofuran-acetonitrile; the detection wavelength was 235 nm; the injection volume was 10 μL;the flow rate was 1.0 ml · min-1; the column temperature was 30 ℃; the running time was 30 min. A HALO 90A AQ-C18 column (3.0×30 mm, 2 µm) was used; the mobile phase A was 95% water/5% acetonitrile (0.1% formic acid), and mobile phase B was 95% acetonitrile/5% water (0.1% formic acid), with gradient elution; the flow rate was 0.6 mL · min-1; the auto-sampler temperature was 4 ℃; the running time was 2.30 min, and the injection volume was 8.00 μL. The mass spectrometry conditions were as follows: electrospray ionization source, positive ion mode, curtain gas was 35 psi, collision gas was 10 psi, spray voltage was 4500 V, nebulizer temperature was 500 ℃, nebulizer and auxiliary gas were both 50 psi. The m/z of nimodipine was 417.18→122.20, and that of dexamethasone was 437.10→361.00. The contents of nimodipine concentration for injection and Nimotop® injection after mixing with different solutions were determined using HPLC, and plasma concentrations of nimodipine following administration were measured using HPLC-MS/MS in Beagle dogs. The pharmacokinetic parameters were calculated using WinNonlin 8.3.4 software, and the main pharmacokinetic parameters were statistically analyzed using SPSS Statistics 26 software. Results: The nimodipine concentration for injection demonstrated good compatibility with the test solutions, and the content of the novel nimodipine formulation remained stable with no significant change within 48 h after compatibility. In contrast, the content of the original preparation agent decreased significantly after compatibility, accompanied by visible crystal formation. There were no significant differences in Cmax, Tmax and AUC of the novel nimodipine formulation compared with the original preparation agent (P>0.05). Conclusion: Nimodipine Concentration for injection exhibits good stability and does not change the pharmacokinetic characteristics of the API, suggesting good clinical application prospects.
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