Validation And Specificity Study On The Test Of 4-aminophenol In The Acetaminophen-containing Drug Products

• By: CHUN, In Koo (Research foundation for pharmaceutical quality, South Korea)
• Co-author(s): Prof. In Koo Chun (Research foundation for pharmaceutical quality, Seoul, South Korea)
  Ms. Hyunju Jeong (Research foundation for pharmaceutical quality, Seoul, South Korea / ChungAng University, Seoul, South Korea)
  Ms. Kyu yeon Kim (Caleb Multilab Inc., Seoul, South Korea)
  MS. Junghwa Lee (Caleb Multilab Inc., Seoul, South Korea)
  Dr. Hye Jung Lee (Caleb Multilab Inc., Seoul, South Korea)
  
• Abstract:

  4-Aminophenol (4-AP), the main degradation product of acetaminophen (AAP), has been controlled by monographs of USP, EP, BP and ChP. The quantity of 4-AP needs to be strictly controlled as it has nephrotoxic effects. As an example, USP specifies that the quantity of 4-AP is not more than 0.15% of labeled amount of AAP in drug products. USP general chapter <227> requires a ternary gradient mobile phase which needs a quaternary gradient HPLC pump, which is not popular. In this study, the validation and specificity of 4-AP in the presence of other combined active pharmaceutical ingredients (APIs) and three kinds of complex AAP tablets were investigated by using a binary gradient mobile phase so as to use a more popular binary gradient HPLC pump. Twenty one kinds of APIs were used for the specificity study and three commercial AAP-containing complex tablets were used for validation study of 4-AP test using a more convenient binary mobile phase according to the chromatographic adjustments described in the USP general chapter <227>. As a result, the specificity, linearity, accuracy, precision, detection limit and quantitation limit were acceptable with the guideline of validation of analytical procedures in KP. In addition, All APIs adopted have no interference in the specificity of 4-AP analysis. In conclusion, this binary mobile phase may be used as an alternative for the control of 4-AP in acetaminophen-containing drug products. This research was supported by a grant (22204MFDS102) from Ministry of Food and Drug Safety in 2022.