title: The Influence of Plasma Albumin Concentration on the Analysis Methodology of Free Valproic Acid by Ultrafiltration and Its Application to Therapeutic Drug Monitoring.
abstract: BACKGROUND
  Free drug analysis is increasingly becoming popular in therapeutic drug monitoring (TDM). Centrifugal ultrafiltration (CF-UF) is the primary method to separate free drug from that of bound drug. However, the volume ratio of ultrafiltrate to sample solution (Vu/Vs) affects the accuracy of CF-UF, which highly depends on the different plasma conditions. Plasma protein concentrations in patients are different from those observed in healthy subjects, and there are also significant differences among patients with different diseases. Only very few studies have reported on the effect of protein concentration on the analysis methodology of free drug by CF-UF.
  
  
  METHODS
  In this study, valproic acid was used as the representative drug, and plasma samples with different albumin concentrations were analyzed by CF-UF and hollow fiber centrifugal ultrafiltration (HFCF-UF).
  
  
  RESULTS
  There was no significant difference of free drug concentrations by HFCF-UF and CF-UF when plasma albumin concentrations ranged 40-60 g/L. However, at low albumin concentrations (<40 g/L), a considerable difference was detected, and the difference was increased with the decrease of plasma albumin concentration. When the albumin concentration was as low as 10 g/L, the free drug concentration was 17.3 mcg/mL by CF-UF, whereas it was 10.2 mcg/mL by HFCF-UF.
  
  
  CONCLUSIONS
  The accuracy of free drug measurement by CF-UF was albumin concentration dependent. However, such an effect was not observed when samples were prepared by HFCF-UF, which was more suitable for TDM of plasma samples from different patients. Therefore, this method could be readily applied to the measurement of free valproic acid plasma concentrations for TDM in patients.
authors.affiliation: *Department of Pharmacy, The Second Hospital of Hebei Medical University; †Department of Pharmaceutical Analysis, School of Pharmacy; ‡Department of Clinic, School of Clinic, Hebei Medical University; and §Department of Clinical Laboratory, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Zhi-Qing
authors.initials: ZQ
authors.lastname: Zhang
authors.forename: Wei-Chong
authors.initials: WC
authors.lastname: Dong
authors.forename: Xiu-Ling
authors.initials: XL
authors.lastname: Yang
authors.forename: Jin-Feng
authors.initials: JF
authors.lastname: Zhang
authors.forename: Xin-Hui
authors.initials: XH
authors.lastname: Jiang
authors.forename: Shao-Jun
authors.initials: SJ
authors.lastname: Jing
authors.forename: Hong-le
authors.initials: HL
authors.lastname: Yang
authors.forename: Ye
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002498:Centrifugation / Q000379:methods; D002648:Child; D002675:Child, Preschool; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D012709:Serum Albumin / Q000378:metabolism*; D014462:Ultrafiltration / Q000379:methods*; D014635:Valproic Acid / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D012709:Serum Albumin; D014635:Valproic Acid