Quantitative acetaminophen analytics
Inventors
GRIMMLER, Matthias • Thônges, Detlef • Schu, Pia • Menzenbach, Carolin • Kreckel, Laura
Assignees
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Publication Number
US-12012630-B2
Publication Date
2024-06-18
Expiration Date
Abstract
A method for quantitatively determining the amount of acetaminophen in a sample with greater precision, greater sensitivity and fewer interactions and fewer spectral and chemical interferences with other compounds contained in the sample. The method includes acetaminophen being hydrolyzed and the resulting p-aminophenol being reacted with a compound of general formula (III): in the presence of an oxidant to form a compound of general formula (IV): wherein R1 and R2, independently of one another, are selected from H, —CH3, and —OCH3, R3 is —C2H5 and R4 is a C1-4 alkyl moiety with a terminal sulfonate group, with the proviso that at least one of R1 and R2 is —OCH3 and/or R4 additionally has at least one OH substituent, and then the amount of the compound of general formula (IV) in the reaction mixture being photometrically determined.
Core Innovation
The invention relates to a method for quantitatively determining an amount of acetaminophen in a sample. The method produces a reaction mixture by hydrolyzing acetaminophen having formula (I) to form p-aminophenol having formula (II), and the formed p-aminophenol is then reacted with a compound of general formula (III) in the presence of an oxidant to form a compound of general formula (IV).
The coupling chemistry is defined by substituent constraints in formulae (III) and (IV): R1 and R2, independently of one another, are selected from H, −CH3, and −OCH3; R3 is −C2H5; and R4 is a substituted C1-4 alkyl moiety with a terminal sulfonate group. A proviso requires that at least one of R1 and R2 is −OCH3 and/or that R4 additionally comprises at least one OH substituent.
The amount of the compound of general formula (IV) in the reaction mixture is photometrically determined. The partial content describes photometric readout in a wavelength range of 400–800 nm, preferably 650–800 nm, and use for sample types including blood, blood serum, and blood plasma.
Claims Coverage
The partial content includes one independent claim directed to a quantitative acetaminophen determination method, with dependent claims that refine oxidant selection, photometric wavelength range, sample matrix, sample volume, and pH conditions. The inventive features are concentrated in the defined hydrolysis-to-coupling-to-photometric-determination sequence combined with specific substituent, sulfonate, and −OCH3/OH provisos for the coupling agent(s) and the resulting product.
Hydrolysis-to-coupling-to-photometric determination sequence for acetaminophen
Producing a reaction mixture by hydrolyzing acetaminophen having formula (I) to form p-aminophenol having formula (II), reacting the p-aminophenol having formula (II) with a compound of general formula (III) in the presence of an oxidant to form a compound of general formula (IV), and photometrically determining an amount of the compound of general formula (IV) in the reaction mixture.
Defined coupling-agent substituents with −OCH3/OH and terminal sulfonate constraints
In formulae (III) and (IV), R1 and R2, independently of one another, are selected from H, −CH3, and −OCH3; R3 is −C2H5; and R4 is a substituted C1-4 alkyl moiety with a terminal sulfonate group, with the proviso that at least one of R1 and R2 is −OCH3 and/or R4 additionally comprises at least one OH substituent.
Specified oxidant options for the oxidant in the coupling step
The oxidant is selected from hydrogen peroxide, an organic peroxide, an iron-cyanide complex, a periodate salt, or a periodate complex.
Photometric wavelength range for the compound of general formula (IV)
The compound of general formula (IV) has an absorption maximum in the 650 nm to 800 nm wavelength range.
Use for blood-derived liquid samples
The method is applied to a liquid sample selected from blood, blood serum, or blood plasma.
Use with very small sample volume
The method is applied to a liquid sample having a volume of 5 μL or less.
pH range for performing the method
The method is performed at a pH between 8 and 10.5.
The core inventive concept is a quantitative acetaminophen assay based on hydrolyzing acetaminophen to p-aminophenol, reacting p-aminophenol with a coupling compound of general formula (III) in the presence of an oxidant to form a product of general formula (IV), and photometrically determining the amount of that product. The main chemical novelty is the defined substituent pattern, while the dependent claims further narrow oxidant type, absorption maximum wavelength range, sample matrix, sample volume, and pH.
Stated Advantages
Improved precision/sensitivity.
Reduced spectral and chemical interferences, including from bilirubin, haemoglobin/haemolysis, and N-acetylcysteine.
Enables very small sample volumes.
Photometric readout in the 400–800 nm range, preferably 650–800 nm.
Documented Applications
Quantitatively determining an amount of acetaminophen in a sample using blood, blood serum, or blood plasma as the liquid sample.
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