Phytomenadione, also known as Phytonadione, Phylloquinone, or Vitamin K1, is a naturally occurring fat-soluble vitamin and an important pharmaceutical active ingredient. It is primarily associated with vitamin K activity and plays a key role in the normal synthesis of several coagulation factors in the liver. Because of its established pharmacological importance, phytomenadione is used in pharmaceutical preparations designed to address vitamin K deficiency and support normal blood coagulation.
Phytomenadione CAS Number 84-80-0 identifies the vitamin K1 active substance. The compound has the molecular formula C31H46O2 and a molecular weight of 450.70 g/mol. Unlike many crystalline small-molecule APIs, phytomenadione is an oily, lipophilic substance and is highly sensitive to light. Its physical and chemical characteristics make appropriate handling, protection from light, and controlled storage important considerations during pharmaceutical manufacturing.
Phytomenadione belongs to the vitamin K family and contains a substituted naphthoquinone structure with a long phytyl side chain. Its lipophilic nature means that it is practically insoluble in water but compatible with suitable organic and lipid-based environments.
In pharmaceutical applications, phytomenadione is incorporated into different dosage forms depending on the intended use. Vitamin K1 preparations may be formulated as injectable products, oral products, or other pharmaceutical presentations. The API is particularly relevant where vitamin K activity is required as part of the management of coagulation-related conditions or vitamin K deficiency.
A notable characteristic of phytomenadione is its E/Z-isomer composition. Pharmacopoeial quality control therefore considers not only the overall phytomenadione content but also the level of the Z-isomer. This makes chromatographic purity and isomer-related testing important elements of pharmaceutical quality control.
Phytomenadione quality is particularly dependent on chromatographic evaluation because the substance is defined in pharmacopoeial standards in terms of phytomenadione isomers. The USP substance specification describes phytomenadione as a mixture of E- and Z-isomers and specifies an overall content of NLT 97.0% and NMT 103.0% of phytomenadione isomers, calculated as C31H46O2. The USP specification also limits the Z-isomer to NMT 21.0%.
These requirements are important when evaluating phytomenadione API because a simple assay value alone does not fully describe the quality of the substance. Appropriate chromatographic testing helps establish identity, overall content, and isomeric composition.
It is important to distinguish bulk API specifications from finished dosage-form specifications. For example, the BP injection monograph specifies 90.0–115.0% of the stated amount for phytomenadione injection. That is a dosage-form requirement and should not be presented as the assay specification for bulk phytomenadione API.
Phytomenadione is a strongly lipophilic compound with very limited water compatibility. Its oily physical nature also means that conventional melting-point specifications used for many crystalline APIs are not necessarily appropriate as a universal API release parameter.
The substance is light-sensitive, so exposure to strong light should be minimized during manufacturing, testing, packaging, and storage. Pharmacopoeial and pharmaceutical handling requirements should therefore be considered when establishing packaging and storage conditions.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 97.0–103.0% |
| Loss on Drying | NMT 1.0% |
| Residue on Ignition | NMT 0.1% |
| Individual Impurity | NMT 0.5% |
| Water Content | NMT 0.5% |