ABSTRACT
Objective To establish inductively coupled plasma mass spectrometry(ICP-MS) method and determine the migration contents of twelve elements in clevidipine injectable emulsion direct contact with packaging materials.Methods Clevidipine injectable emulsion were digested by carbonization-oxidation.Based on internal standard method, migration contents of twelve elements in digested sample solutions were analyzed by ICP-MS.Results The linear correlative coefficients for twelve elements were higher than 0.9995.The accuracy, precision and stability of the method were detected, all of which conformed to the analysis standard.The recoveries were in the range of 81.3%~119.0%.Conclusion The packaging materials have good compatibility with injectable emulsion, and migration contents of Na、K、Sb and Ba of twelve elements meet the requirements.
ABSTRACT
OBJECTIVE: To develop an LC-MS/MS method for simultaneous determination of clevidipine and its major metabolite H152/81 concentration in rat plasma. METHODS: The plasma samples were processed with liquid-liquid extraction, with nimo-dipin as an internal standard. The separation was achieved on ZORBAX SB C18 column (2.1 mm×100 mm, 3.5 μm) and eluted with linear gradient using acetonitrile and 0.1% formic acid at the flow rate of 0.3 mL·min-1, the injection volume was 10 μL and the column temperature was maitained at 30℃. The total time of the analysis was 3.5 min. Detection of the analytes were achieved using positive ion electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. RESULTS: The linear calibration curve of clevidipine and its major metabolite H152/81 were obtained concentration range of 1.0-200 μg·L-1 (r>0.99), with the lower limit of quantitation (LLOQ) of 1.0 μg·L-1. The average recovery was between 92.5%-109.8%, Intra-day and inter-day relative standard deviations were both below 15%. The recoveries of low, middle and high concentrations were 71.3%-82.6%, respectively. CONCLUSION: The established method is rapid, sensitive, accurate, specific and reliable, and suitable for simultaneous determination of clevidipine and its major metabolite H152/81 in rat plasma.
ABSTRACT
@#To evaluate pharmacokinetic and metabolic characteristics of clevidipine butyrate lipid microspheres(CDB-LM)injection in mice, a novel HPLC-FLD method was developed for simultaneous measurement of clevidipine butyrate(CDB)and its metabolites clevidipine acid(MI)in whole blood samples. The chromatographic column was Waters C18(4. 6 mm×150 mm, 5 μm)and the mobile phase is consisted of acetonitrile-methanol-phosphate(2 ∶1 ∶2). The detection wavelength of FLD included excitation wavelength at 358 nm and emission wavelength at 440 nm. The pharmacokinetic parameters of CDB and MI were calculated by using DAS 2. 0. Then obtained parameters were statisticaly analyzed using PASW Statistics 18. The results showed that the half-life of CDB and MI were about 4 min and 20 min, respectively. Pharmacokinetic parameters of the low- and high-dose groups were as follows: CL of CDB were 4. 21 and 2. 72 L ·min-1 ·kg-1; AUC0-t were 3. 86 and 6. 43 mg/L ·min; MRT0-t were 7. 09 and 6. 17 min. CL of MI were 0. 34 and 0. 22 L ·min-1 ·kg-1; AUC0-t were 52. 23 and 74. 90 mg/L ·min; MRT0-t were 201. 24 and 217. 33 min. A method of protein precipitation was established, and acetonitrile was used to deal with whole blood samples. This method was simple, fast, with no interference with endogenous impurities. The results showed that the established HPLC-FLD method was simple and sensitive. It can be used to determine CDB and MI simultaneously. Comparing the low-dose group with the high-dose group, it was found that the plasma concentration-time curve of the two groups revealed the same tendency, which confirms that CDB has a short half-life and that it metabolizes to MI quickly.