PMID- 28535452 OWN - NLM STAT- MEDLINE DCOM- 20180119 LR - 20181202 IS - 1873-264X (Electronic) IS - 0731-7085 (Linking) VI - 142 DP - 2017 Aug 5 TI - Highly sensitive UHPLC-MS/MS method for the simultaneous estimation of propafenone and its metabolites 5-hydroxypropafenone and N-depropylpropafenone on human dried blood spots technique and application to a pharmacokinetic study. PG - 328-336 LID - S0731-7085(17)30851-8 [pii] LID - 10.1016/j.jpba.2017.04.046 [doi] AB - A highly sensitive, rapid and selective UHPLC-MS/MS method has been developed and validated for quantification of the propafenone (PF), 5-hydroxypropafenone (5-OHPF) and N-depropylpropafenone (N-DPF) on human dried blood spot (DBS). The assay procedure involves a solid-liquid extraction of PF, 5-OHPF and N-DPF and amlodipine (internal standard, I.S.) from dried human DBS cards using water and acetonitrile. The chromatographic resolution was achieved on a BEH C(18) column using a gradient mobile phase consisting of 0.1% formic acid in water and acetonitrile with 0.1% formic acid at flow rate of 0.6mL/min. The UHPLC-MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. Total run time of analysis was 1.1min and elution of PF, 5-OHPF, N-DPF and I.S. occurred at 0.69, 0.6, 0.68 and 0.73min, respectively. A detailed method validation was performed as per the regulatory guidelines and the standard curves found to be linear in the range of 5.11-1000ng/mL for PF and 5-OHPF and 0.51-100ng/mL for N-DPF with a correlation coefficient of >/=0.99 for all the drugs. The intra- and inter-day accuracies were in the range of 95.6-107 and 93.5-103; 93.4-106 and 96.3-107 and 87.9-103 and 96.5-102%, for PF, 5-OHPF and N-DPF, respectively. The intra- and inter-day precisions were in the range of 2.50-5.52 and 3.38-5.18; 2.16-6.34 and 3.23-4.94 and 2.63-7.55 and 1.56-10.2%, for PF, 5-OHPF and N-DPF, respectively. The validated assay method was successfully applied to a pharmacokinetic study in humans. The key pharmacokinetic parameters AUC(0-infinity) and C(max) were 6057+/-1526, 2002+/-515 and 525+/-202 ng*h/mL and 653+/-183, 295+/-37.5 and 68.4+/-13.6ng/mL for PF, 5-OHPF and N-DPF, respectively. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Andy, Adinarayana AU - Andy A AD - Department of Biotechnology, Acharya Nagarjuna University, Nagarjuna Nagar, Guntur, 522510, Andhra Pradesh, India. FAU - Kallem, Raja Reddy AU - Kallem RR AD - Science Office, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, 79106, United States. FAU - Mullangi, Ramesh AU - Mullangi R AD - Jubilant Biosys, 2nd Stage, Industrial Suburb, Yeshwanthpur, Bangalore, 560 022, India. Electronic address: mullangi_ramesh@jubilantinnovation.com. FAU - Andy, Divya AU - Andy D AD - Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, 3000 Arlington Avenue, Toledo OH 43614, United States. FAU - Seshagiri Rao, J V L N AU - Seshagiri Rao JVLN AD - Department of Biotechnology, Acharya Nagarjuna University, Nagarjuna Nagar, Guntur, 522510, Andhra Pradesh, India; College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, 530 003, Andhra Pradesh, India. LA - eng PT - Journal Article DEP - 20170511 PL - England TA - J Pharm Biomed Anal JT - Journal of pharmaceutical and biomedical analysis JID - 8309336 RN - 68IQX3T69U (Propafenone) RN - 7AC8BF38NP (5-hydroxypropafenone) RN - KN087PHW5T (N-depropylpropafenone) SB - IM MH - Chromatography, High Pressure Liquid MH - *Dried Blood Spot Testing MH - Humans MH - Propafenone/analogs & derivatives MH - Reproducibility of Results MH - Tandem Mass Spectrometry OTO - NOTNLM OT - 5-hydroxypropafenone OT - Bioanalysis OT - DBS OT - Human blood OT - LC-MS/MS OT - Method validation OT - N-depropylpropafenone OT - Pharmacokinetics OT - Propafenone EDAT- 2017/05/24 06:00 MHDA- 2018/01/20 06:00 CRDT- 2017/05/24 06:00 PHST- 2017/04/05 00:00 [received] PHST- 2017/04/25 00:00 [revised] PHST- 2017/04/28 00:00 [accepted] PHST- 2017/05/24 06:00 [pubmed] PHST- 2018/01/20 06:00 [medline] PHST- 2017/05/24 06:00 [entrez] AID - S0731-7085(17)30851-8 [pii] AID - 10.1016/j.jpba.2017.04.046 [doi] PST - ppublish SO - J Pharm Biomed Anal. 2017 Aug 5;142:328-336. doi: 10.1016/j.jpba.2017.04.046. Epub 2017 May 11.