Introduction of qNMR to the Japanese Pharmacopoeia (JP) for specification of marker compounds used for standardization of herbal medicines

In Japan, standardization of herbal medicines is mostly controlled by the Japanese Pharmacopoeia (JP). JP16 contains the monographs of 217 crude drugs inculding powders, 22 Kampo extracts and 32 crude drug preparations other than Kampo extracts. The specific marker compound for quantification is very important for standardization of herbal medicines. Therefore, JP has prepared several marker compounds as JP Certified Reference Standards (JP-CRS), which are highly purified and of which the water contents are known. But, it is difficult to prepare them because of the following reason. The synthesis of natural compound is not so easy in most cases. Therefore the targeted compound is separated from natural materials with a great deal of effort requiring high economical cost. 2) Karl Fischer method is necessary to determine water contents precisely, and consequently the valuable separated compounds are consumed for the determination of water content and this also leads to high economical cost. Considering these difficulties, JP utilizes many chemical reagents commercially available as reference standards for quantitative analyses instead of JP-CRS. However, there is no information on their absolute purity. In order to solve the issues, in 2009 the JP experimental group started the joint research [1] for utilizing quantitative NMR (qNMR) to determine the absolute purity of chemical reagents used for assay of herbal medicines. As a result, in 2013, four reference standards (geniposide, magnolol, paeonol and magnoflorine) having absolute purity values determined by qNMR in a reagent company are available in the markets and the quantitative HPLC assays by using these reference standards will appear in several monographs in JP16 supplement 2.

References:

[1] Hosoe J. et al., Pharmaceutical and Medical Device Regulatory Science, 41, 960 – 970 (2010); [2] Hosoe J. et al., ibid., 43, 182 – 193 (2012); JP16 Supplement 1: http://www.mhlw.go.jp/topics/bukyoku/iyaku/yakkyoku/english.html