Pharmacokinetic study of L-5-methyltetrahydrofolate calcium in spraguedawley rat
10.13699/j.cnki.1001-6821.2018.03.036
- VernacularTitle:L-5-甲基四氢叶酸钙在SD大鼠体内的药代动力学研究
- Author:
Si-Yang NI
1
;
Yu-Yang DAI
;
Feng WU
;
Shu-Min WANG
;
Shao-Jie GUO
;
Hui ZHOU
;
Xiu-Li ZHAO
Author Information
1. 首都医科大学附属北京同仁医院国家药物临床试验机构
- Keywords:
5-methyltetrahydrofolic acid calcium;
SD rat;
high-performance liquid chromatography-tandem mass spectrometry;
pharmacokinetics
- From:
The Chinese Journal of Clinical Pharmacology
2018;34(3):307-311
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the pharmakinetics of 5-methyltetra-hydrofolic acid (5-MTHF) in SD rats by a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).Methods Six male SD rats weregiven 1.5 × 10-2 mmol · L-1 · kg-1 5-MTHF,and blood was drawn for analysis by HPLC-MS/MS.The plasma was handled by protein precipitation,chromatographic column:Grace Altima HP C18,mobile phases A was methanol-acetonitrile-isopropanol-ethanol-water-formic acid-dimethyl sulphoxide (25∶ 25∶ 25 ∶ 25∶ 0.1 ∶ 1) and mobile phases B was methanol-water-formic acid (10 ∶ 90 ∶ 0.1),gradient elution,flow rate was 0.40 mL · min-1 The method validation was conducted by investigating linear range,accuracy and precision,stability,recovery and matrix effects.The pharmacokinetic parameters were calculated by WinNonlin.Results The method had a linear range of 10.00-1.00 × 104 ng · mL-1 with good correlation,and the regression equation was y =1.01 × 10-3x + 1.82 × 10-3(r =0.998 3).The intra-day and inter-day accuracy and precision,the recovery,the matrix effects,and the stability were also validated and met the requirement.Pharmacokinetic parameters:the t1/2was (15.23 ± 5.76)h,and AUC0-t was (2788.52 ± 348.86)ng· mL-1 · h without baseline 5-MTHF concentration deduction;the t1/2 was (1.57 ±0.34)h,and AUC0-t was (971.80 ±237.58)ng · mL-1 · h with deduction of the baseline 5-MTHF concentration.Conclusion A sensitive and accurate HPLC-MS/MS method was developed for the determination of 5-MTHF.