TY - JOUR
T1 - A rapid and sensitive microscale HPLC method for the determination of indomethacin in plasma of premature neonates with patent ductus arteriousus
AU - Al Za'abi, M. A.
AU - Dehghanzadeh, G. H.
AU - Norris, R. L.G.
AU - Charles, B. G.
N1 - Funding Information:
We thank Prof. L. Marnett (Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN, USA) for providing the indomethacin esters, and to Alphapharm Pty Ltd. (Carole Park, Qld, Australia) for providing the indomethacin reference material. We thank Professor D. Tudehope and Dr. P. Woodgate (Division of Neonatology, Mater Health Services, Brisbane, Qld, Australia) and Dr T. Donovan (Grantley Stable Neonatal Unit, Royal Brisbane Women's Hospital, Brisbane, Qld, Australia) for access to their patients. A Fellowship in Therapeutic Drug Monitoring provided to Dr. Dehghanzadeh by the Iranian Ministry of Health is gratefully acknowledged. We also acknowledge the provision of a Ph.D. scholarship to Dr. Al Za’abi by the Sultan Qaboos University (Muscat, Oman).
PY - 2006/1/18
Y1 - 2006/1/18
N2 - Indomethacin (IND) is the drug of choice for the closure of a patent ductus arteriosus (PDA) in neonates. This paper describes a simple, sensitive, accurate and precise microscale HPLC method suitable for the analysis of IND in plasma of premature neonates. Samples were prepared by plasma protein precipitation with acetonitrile containing the methyl ester of IND as the internal standard (IS). Chromatography was performed on a Hypersil C 18 column. The mobile phase of methanol, water and orthophosphoric acid (70:29.5:0.5, v/v, respectively), was delivered at 1.5 mL/min and monitored at 270 nm. IND and the IS were eluted at 2.9 and 4.3 min, respectively. Calibrations were linear (r > 0.999) from 25 to 2500 μg/L. The inter- and intra-day assay imprecision was less than 4.3 % at 400-2000 μg/L, and less than 22.1% at 35 μg/L. Inaccuracy ranged from -6.0% to +1.0% from 35 to 2000 μg/L. The absolute recovery of IND over this range was 93.0-113.3%. The IS was stable for at least 36 h when added to plasma at ambient temperature. This method is suitable for pharmacokinetic studies of IND and has potential for monitoring therapy in infants with PDA when a target therapeutic range for IND has been validated.
AB - Indomethacin (IND) is the drug of choice for the closure of a patent ductus arteriosus (PDA) in neonates. This paper describes a simple, sensitive, accurate and precise microscale HPLC method suitable for the analysis of IND in plasma of premature neonates. Samples were prepared by plasma protein precipitation with acetonitrile containing the methyl ester of IND as the internal standard (IS). Chromatography was performed on a Hypersil C 18 column. The mobile phase of methanol, water and orthophosphoric acid (70:29.5:0.5, v/v, respectively), was delivered at 1.5 mL/min and monitored at 270 nm. IND and the IS were eluted at 2.9 and 4.3 min, respectively. Calibrations were linear (r > 0.999) from 25 to 2500 μg/L. The inter- and intra-day assay imprecision was less than 4.3 % at 400-2000 μg/L, and less than 22.1% at 35 μg/L. Inaccuracy ranged from -6.0% to +1.0% from 35 to 2000 μg/L. The absolute recovery of IND over this range was 93.0-113.3%. The IS was stable for at least 36 h when added to plasma at ambient temperature. This method is suitable for pharmacokinetic studies of IND and has potential for monitoring therapy in infants with PDA when a target therapeutic range for IND has been validated.
KW - HPLC
KW - Indomethacin
KW - Patent ductus arteriosus
KW - Premature neonates
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U2 - 10.1016/j.jchromb.2005.11.025
DO - 10.1016/j.jchromb.2005.11.025
M3 - Article
C2 - 16326151
AN - SCOPUS:30444438034
SN - 1570-0232
VL - 830
SP - 364
EP - 367
JO - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
JF - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
IS - 2
ER -