title: Analysis of nifedipine in human plasma and amniotic fluid by liquid chromatography-tandem mass spectrometry and its application to clinical pharmacokinetics in hypertensive pregnant women.
abstract: Nifedipine is a dihydropyridine calcium channel blocker used for the treatment of hypertension in pregnant women. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for analysis of nifedipine in human plasma and amniotic fluid. Separation of nifedipine and nitrendipine (IS) was performed using a LiChroCART(®) RP-Select B column and a mixture of water:acetonitrile:glacial acetic acid (30:70:0.5 v/v) as the mobile phase. Aliquots of 500μL of biological samples were extracted at pH 13 using dichloromethane:n-pentane (3:7 v/v). The validated method was applied to a study of the pharmacokinetics of nifedipine in human plasma and amniotic fluid samples collected up to 12h after administration of the last slow-release nifedipine (20mg/12h) dose to 12 hypertensive pregnant women. The estimated pharmacokinetic parameters of nifedipine showed a mean AUC(0-12) of 250.2ngh/mL, ClT/F of 89.2L/h, Vd/F of 600.0L and t1/2 5.1h. The mean amniotic fluid/plasma concentration ratio was 0.05. The methods proved to be highly sensitive by showing a lower quantification limit of 0.1ng/mL for both matrices. And this study reports for the first time the complete development and validation of the method to quantify nifedipine in amniotic fluid using LC-MS-MS.
authors.affiliation: Department of Obstetrics and Gynecology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Gabriela Campos de Oliveira
authors.initials: GC
authors.lastname: Filgueira
authors.affiliation: Department of Obstetrics and Gynecology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Osmany Alberto Silva
authors.initials: OA
authors.lastname: Filgueira
authors.affiliation: Department of Obstetrics and Gynecology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Daniela Miarelli
authors.initials: DM
authors.lastname: Carvalho
authors.affiliation: Department of Clinical, Toxicologic and Bromatologic Analyses, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Maria Paula
authors.initials: MP
authors.lastname: Marques
authors.affiliation: Department of Obstetrics and Gynecology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Elaine Christine Dantas
authors.initials: EC
authors.lastname: Moisés
authors.affiliation: Department of Obstetrics and Gynecology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Geraldo
authors.initials: G
authors.lastname: Duarte
authors.affiliation: Department of Clinical, Toxicologic and Bromatologic Analyses, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Vera Lucia
authors.initials: VL
authors.lastname: Lanchote
authors.affiliation: Department of Obstetrics and Gynecology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. Electronic address: rcavalli@fmrp.usp.br.
authors.forename: Ricardo Carvalho
authors.initials: RC
authors.lastname: Cavalli
mesh_terms: D000328:Adult; D000653:Amniotic Fluid / Q000737:chemistry*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D009543:Nifedipine / Q000008:administration & dosage / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000188:drug therapy*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D009543:Nifedipine
keywords: LC-MS/MS; Nifedipine; Pharmacokinetics; Pregnancy, Hypertensive