Plasma and cerebrospinal fluid pharmacokinetics of hydroxysafflor yellow A in patients with traumatic brain injury after intravenous administration of Xuebijing using LC-MS/MS method.

Hydroxysafflor yellow A (HSYA) is the most pharmaceutically relevant compound in Xuebijing (XBJ) for traumatic brain injury (TBI) treatment. We aimed to investigate biofluids pharmacokinetics of HSYA from XBJ to ensure the drug safety and to guide the clinical use.A sensitive, rapid and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was applied to investigate pharmacokinetics of HSYA in TBI patients after intravenous administration of XBJ. Non-compartmental methods using DAS 3.0 software were applied to analyse the pharmacokinetic parameters.A similar half-life (Plasma _{t 1/2} : 14.55 ± 3.51 h vs. CSF _{t 1/2} : 15.73 ± 3.63) was observed. HSYA reached the peak level rapidly, but exhibited a strongly slow absorption phase from blood to cerebrospinal fluid (CSF, Plasma _Tmax : 0.69 ± 0.26 h vs. CSF _Tmax : 4.0 ± 2.62 h). HSYA exhibited much higher C _max (Plasma _Cmax : 9342.76 ± 2489.23 μg/L vs. CSF _Cmax : 98.08 ± 14.51 μg/L) and AUC _0-t (Plasma _AUC0-t : 57490.5 ± 5560.3 μg h/L vs. CSF _AUC0-t : 1851.6 ± 269.1 μg h/L), yet a shorter CL (Plasma _CL : 0.02 ± 0.002 L/h/kg vs. CSF _CL : 0.55 ± 0.01 L/h/kg) in plasma than in CSF. The AUC _CSF / AUC _plasma of HSYA was almost 3.37%.In summary, the results demonstrate that part of HSYA come across blood-brain barrier after XBJ administration. This study provides evidence for better understanding the pharmacokinetics and potential for clinical guidance of XBJ for TBI treatment.