Determination of Menaquinone-4 in Plasma after Administration of Menaquinone-4 Dosage Forms in Healthy Human Subjects

Open Access
Publisher Website
Google Scholar
Abstract
A sensitive method for determination of menaquinone-4 (vitamin K2 (20), MQ-4) in the plasma by mass fragmentography was developed. In this method, microquantitative reductive acetylation was studied for the conversion of MQ-4 to volatile derivative. Then the concentration of MQ-4 in the plasma after the single administration of MQ-4 dosage forms (30-120 mg/man) to healthy male adult volunteers and the bioavailabilities of the dosage forms were examined. MQ-4 and phylloquinone (vitamin K1, PQ) were extracted from the plasma to which PQ was addded as an internal standard (IS). The extracts were dissolved in acetylating reagent (acetic anhydride-acetic acid-sodium acetate) and Zn dust was added, then refluxed for 1 h at 170.degree. C in a sealed glass tube. MQ-4 and PQ were converted to dihydromenaquinone-4 diacetate and dihydrophylloquinone diacetate, respectively, and measured by mass fragmentography. The determination limit was 3 ng/ml plasma. MQ-4 given in syrup was absorbed more rapidly than that in capsule. The maximum plasma concentration (Cmax) for i.m. administration was lower than that for syrup, but then the concentration decreased very slowly. The plasma concentration after i.v. administration decreased apparently in a linear 3-compartment model. The area under concentration-time curve (AUC) after the oral administration of syrup or capsule was observed to be in proportion to the dose. The bioavailabilities of syrup and capsule were 38 and 29%, respectively.