Determination of phenazopyridine in human plasma via LC-MS and subsequent development of a pharmacokinetic model.
This paper describes a new LC-MS method for the determination of phenazopyridine and the subsequent development of a pharmacokinetic model for phenazopyridine in vivo. Phenazopyridine hydrochloride is a strong analgesic used in the treatment of urinary tract infections. Although it has been used as a clinical treatment for a very long time, pharmacokinetic data and suitable methods for its determination in plasma are currently lacking. The study described in this paper used high performance liquid chromatography-mass spectrometry, HPLC-MS, to determine the plasma concentrations of phenazopyridine in human subjects after oral administration. After liquid-liquid extraction, the phenazopyridine in the plasma was analyzed on a C18 column under SIM mode. A double-peak phenomenon was observed in most of the concentration-time profiles of the subjects. Although some drugs are known to cause this phenomenon, phenazopyridine has not been reported to do so. Several possible causes were analyzed in order to obtain an explanation. We proposed a two-site absorption compartment model to fit the concentration data in vivo, which has one more absorption site than the classical one-compartment model. The model describes the concentration profiles in different dose groups well and could provide an explanation for the double-peak phenomenon. The three dose groups exhibited similar model parameters and a linear pharmacokinetic process over the dose range used.
Shang
Erxin
E
The Center for Instrumental Analysis, China Pharmaceutical University, Mailbox 34, 24# Tong Jia Xiang, Nanjing, 210009, PR China.
Xiang
Bingren
B
Liu
Guangyu
G
Xie
Shaofei
S
Wei
Wenyan
W
Lu
Jun
J
D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006207:Half-Life; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D010621:Phenazopyridine / Q000097:blood* / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity
D010621:Phenazopyridine