Generic placeholder image

Current Chromatography

Editor-in-Chief

ISSN (Print): 2213-2406
ISSN (Online): 2213-2414

Research Article

Development of Urinary Assay Methods for the Estimation of Paracetamol Glucuronide and Paracetamol Sulphate in Preterm Neonates with Patent Ductus Arteriosus

Author(s): Diab Eltayeb Diab and Kannan Sridharan*

Volume 9, Issue 1, 2022

Published on: 14 March, 2022

Article ID: e021221198479 Pages: 5

DOI: 10.2174/2213240608666211202092036

Price: $65

Abstract

Aims: This study aimed to develop a high-performance liquid chromatography (HPLC) technique for estimating paracetamol glucuronide and paracetamol sulphate in the urine samples of preterm neonates.

Background: Validated methods exist for estimating the principal metabolites of paracetamol in older children and those with liver disease. Here, we have developed and validated a simple technique for estimating the same in urine samples of preterm neonates.

Objective: The study aims to develop and validate a simple, reliable, and accurate HPLC technique for estimating urinary paracetamol glucuronide and paracetamol sulphate metabolites.

Methods: Preterm neonates of either sex diagnosed with patent ductus arteriosus (PDA) receiving paracetamol intravenously at the dose of 15 mg/kg every six hours were recruited. We ran the samples under standardized chromatographic conditions and using various dilutions of the calibration standards. Measures of assay selectivity, linearity, accuracy, and precision were estimated.

Results: We observed that the peaks for paracetamol glucuronide and paracetamol sulphate were distinguished from those of the drug-free urine samples. The results for both metabolites revealed good reproducibility, with a percent coefficient of variation (% CV) of 4.3 and 4.9 for the slope for paracetamol glucuronide and paracetamol sulphate, respectively. Similarly, we observed good linearity, as indicated by the correlation coefficients of 0.99 for the metabolites. The validation assays revealed that the method is linear, accurate, and precise over the defined concentration ranges.

Conclusion: We demonstrated that HPLC has good accuracy, reliability, and precision, and it can be used for estimating the principal metabolites from urine samples in neonates for defining the ontogeny of conjugation enzymes and in paracetamol overdose.

Keywords: Paracetamol metabolites, paracetamol sulphate, paracetamol glucuronide, acetaminophen sulphate, acetaminophen glucuronide, urine.

Graphical Abstract
[1]
Ohlsson, A.; Shah, P.S. Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low birth weight infants. Cochrane Database Syst. Rev., 2018, 4(4), CD010061.
[http://dx.doi.org/10.1002/14651858.CD010061.pub3] [PMID: 29624206]
[2]
Flint, R.B.; Mian, P.; van der Nagel, B.; Slijkhuis, N.; Koch, B.C. Quantification of acetaminophen and its metabolites in plasma using UPLC-MS: Doors open to therapeutic drug monitoring in special patient populations. Ther. Drug Monit., 2017, 39(2), 164-171.
[http://dx.doi.org/10.1097/FTD.0000000000000379] [PMID: 28169862]
[3]
Jensen, L.S.; Valentine, J.; Milne, R.W.; Evans, A.M. The quantification of paracetamol, paracetamol glucuronide and paracetamol sulphate in plasma and urine using a single high-performance liquid chromatography assay. J. Pharm. Biomed. Anal., 2004, 34(3), 585-593.
[http://dx.doi.org/10.1016/S0731-7085(03)00573-9] [PMID: 15127815]
[4]
al-Obaidy, S.S.; Li Wan Po, A.; McKiernan, P.J.; Glasgow, J.F.; Millership, J. Assay of paracetamol and its metabolites in urine, plasma and saliva of children with chronic liver disease. J. Pharm. Biomed. Anal., 1995, 13(8), 1033-1039.
[http://dx.doi.org/10.1016/0731-7085(95)01303-3] [PMID: 8580148]
[5]
Sridharan, K.; Al Jufairi, M.; Al Ansari, E.; Al Marzooq, R.; Hubail, Z.; Hasan, S.J.R.; Al Madhoob, A. Intravenous acetaminophen (at 15 mg/kg/dose every 6 hours) in critically ill preterm neonates with patent ductus arteriosus: A prospective study. J. Clin. Pharm. Ther., 2021, 46(4), 1010-1019.
[http://dx.doi.org/10.1111/jcpt.13384] [PMID: 33638909]
[6]
Schmidt, T.C.; Schmitz, O.J.; Teutenberg, T. Multidimensional chromatography. Anal. Bioanal. Chem., 2015, 407(1), 117-118.
[http://dx.doi.org/10.1007/s00216-014-8265-y] [PMID: 25342298]
[7]
Coskun, O. Separation techniques: Chromatography. North. Clin. Istanb., 2016, 3(2), 156-160.
[PMID: 28058406]
[8]
Aboul-Enein, H.Y.; Ali, I. Comparison of the chiral resolution of econazole, miconazole, and sulconazole by HPLC using normal-phase amylose CSPs. Fresenius J. Anal. Chem., 2001, 370(7), 951-955.
[http://dx.doi.org/10.1007/s002160100884] [PMID: 11569882]
[9]
Aboul-Enein, H.Y.; Ali, I. Enantiomeric resolution of some imidazole antifungal agents on chiralpak WH chiral stationary phase using HPLC. Chromatographia, 2001, 54, 200-202.
[http://dx.doi.org/10.1007/BF02492245]
[10]
Ali, I.; Naim, L.; Ghanem, A.; Aboul-Enein, H.Y. Chiral separations of piperidine-2,6-dione analogues on Chiralpak IA and Chiralpak IB columns by using HPLC. Talanta, 2006, 69(4), 1013-1017.
[http://dx.doi.org/10.1016/j.talanta.2005.12.004] [PMID: 18970673]
[11]
Aboul-Enein, H.Y.; Ali, I. Studies on the effect of alcohols on the chiral discrimination mechanisms of amylose stationary phase on the enantioseparation of nebivolol by HPLC. J. Biochem. Biophys. Methods, 2001, 48(2), 175-188.
[http://dx.doi.org/10.1016/S0165-022X(01)00148-8] [PMID: 11356487]
[12]
Ali, I.; Haque, A.; Al-Othman, Z.A. Stereoselective interactions of chiral dipeptides on amylose based chiral stationary phases. Sci. China Chem., 2015, 58, 519-525.
[http://dx.doi.org/10.1007/s11426-014-5239-z]
[13]
Aboul-Enein, H.Y.; Ali, I. Optimization strategies for HPLC enantioseparation of racemic drugs using polysaccharides and macrocyclic glycopeptide antibiotic chiral stationary phases. Farmaco, 2002, 57(7), 513-529.
[http://dx.doi.org/10.1016/S0014-827X(02)01242-9] [PMID: 12164206]
[14]
Ali, I.; Al-Othman, Z.A.; Al-Warthan, A.; Asnin, L.; Chudinov, A. Advances in chiral separations of small peptides by capillary electrophoresis and chromatography. J. Sep. Sci., 2014, 37(18), 2447-2466.
[http://dx.doi.org/10.1002/jssc.201400587] [PMID: 25044566]
[15]
Gama, M.R.; Collins, C.H.; Bottoli, C.B. Nano-liquid chromatography in pharmaceutical and biomedical research. J. Chromatogr. Sci., 2013, 51(7), 694-703.
[http://dx.doi.org/10.1093/chromsci/bmt023] [PMID: 23585638]
[16]
ICH Harmonized Tripartite Guidelines.. Validation of analytical procedures: Text and methodology Q2 (R1), 2021. Available from: https://database.ich.org/sites/default/files/Q2%28R1%29%20 Guideline.pdf.
[17]
Hart, S.J.; Tontodonati, R.; Calder, I.C. Reversed-phase chromatography of urinary metabolites of paracetamol using ion suppression and ion pairing. J. Chromatogr. A, 1981, 225(2), 387-405.
[http://dx.doi.org/10.1016/S0378-4347(00)80287-X] [PMID: 7298773]
[18]
Knox, J.H.; Jurand, J. Determination of paracetamol and its metabolites in urine by high-performance liquid chromatography using ion-pair systems. J. Chromatogr. A, 1978, 149, 297-312.
[http://dx.doi.org/10.1016/S0021-9673(00)80994-2] [PMID: 649733]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy