Study On A Photolytic Product In Vitamin K₁ And Photolysis Degradation Kinetics Of Vitamin K₁

Phytomenadione(VK)₁ is a drug for preventing and healing haemorrhage due to vitamin K deficiency. VK₁ is a mixture of 2-methyl-3-[(2E)-3,7,11,15-tetramethylhexadec-2-enyl]naphthalene-1,4-dione(trans-phytomenadione) and 2-methyl-3-[(2Z)-3,7,11,15-tetramethylhexadec-2-enyl]naphthalene-1,4-dione (cis-phytomenadione). Its structure is as follows,Menadione is the raw material to synthesize VK₁. VK₁ is stable in air, moisture and dilute acid but it is very easily decomposable when exposed to light. It's required for VK₁ in the present compendial monographs(ChP, USP, BP and EP) that the content of menadione should be strict controlled and the other impurities are controlled as related substances using colorimetry or TLC method. But the author found that there was another impurity in VK₁ and its amount was even larger than menadione in some samples of VK₁ and its amount will obviously increase when exposed to light.A column chromatography method was used to prepare the impurity and spectrometric analysis of UV, IR, MS and NMR was carried out to identify its structure. Its structure is 2-methyl-3-(3-hydroxy-3,7,11,15-tetramethyl-1-hexadecenyl)-1,4-naphthoquinone(named as impurity H for short). The physics constants of the impurity was determined as well.Two different HPLC methods were developed to simultaneously determinethe impurities in VKi. One is a liquid-solid adsorption chromatography(LSC), the other one is a reverse phase high-performance liquid chromatography (RP-HPLC). The two methods were validated in terms of linearity, precision, accuracy, specificity, limit of detection(LOD) and quantitation(LOQ).The methods are simple, accurate and suitable for routine analysis of VKi.The research of the photolysis degradation kinetics of VKj was also carried out. The change of the content of VKi accord with zero order reaction.There is no any report about the determination of menadione and the degradation product in VKi using HPLC method and about the photolysis degradation kinetics of VKi. The study results of the author's work provide important theory basis and analysis method for the quality control...