Quantitative high-performance liquid chromatography-based detection method for calphostin C, a naturally occurring perylenequinone with potent antileukemic activity

被引:13
作者
Chen, CL
Chen, H
Zhu, DM
Uckun, FM
机构
[1] Hughes Inst, Dept Pharmaceut Sci, Roseville, MN 55113 USA
[2] Hughes Inst, Dept Immunol, Roseville, MN 55113 USA
[3] Hughes Inst, Drug Discovery Program, Roseville, MN 55113 USA
来源
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES | 1999年 / 724卷 / 01期
关键词
calphostin C; perylenequinone;
D O I
10.1016/S0378-4347(98)00562-3
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Calphostin C is a potent inhibitor of protein kinase C and can induce Ca2+-dependent apoptosis in human ALL cells. Further development of calphostin C will require detailed pharmacodynamic studies in preclinical animal models. Therefore, we established a sensitive and accurate high-performance liquid chromatography (HPLC)-based quantitative detection method for the measurement of calphostin C levels in plasma Extraction of calphostin C from plasma was performed by precipitation of plasma protein using acetonitrile and an aliquot of extracted supernatant was injected onto a Hewlett-Packard HPLC system constituting a 250X4 mm LiChrospher 100, RP-18 (5 pm) in conjunction with a 4X4 mm LiChrospher 100, RP-18 guard column (5 mu m). The eluted compounds were detected by diode array detection set at a wavelength of 479 nm. Acetonitrile-water containing 0.1% trifluoroacetic acid and 0.1% triethylamine (70:30, v/v) was used as the mobile phase. The average extraction recovery from plasma was 97.3%. Good linearity (r>0.999) was observed throughout the concentration range of 0.05-40 mu M for calphostin C in 50 mu l of plasma. Intra- and inter-assay variabilities were less than 6% in plasma. The lowest detection limit of calphostin C in 50 mu l plasma was 0.02 mu M at a signal-to-noise ratio of similar to 3. The availability of this assay will now permit detailed pharmacodynamic and pharmacokinetic studies of calphostin C in vivo. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:157 / 162
页数:6
相关论文
共 34 条
[1]   HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC DETERMINATION OF BRB-I-28, A NOVEL ANTIARRHYTHMIC AGENT, IN DOG PLASMA AND URINE [J].
CHEN, CL ;
LESSELEY, BA ;
CLARKE, CR ;
RODER, JD ;
SANGIAH, S ;
BERLIN, KD ;
GARRISON, GL ;
SCHERLAG, BJ ;
LAZZARA, R ;
PATTERSON, E .
JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS, 1992, 583 (02) :274-279
[2]   DETERMINATION OF GLG-V-13, A NOVEL ANTIARRHYTHMIC AGENT, IN PLASMA AND URINE BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY [J].
CHEN, CL ;
SANGIAH, S ;
RODER, JD ;
CHEN, H ;
BERLIN, KD ;
GARRISON, GL ;
SCHERLAG, BJ ;
LAZZARA, R .
JOURNAL OF LIQUID CHROMATOGRAPHY, 1994, 17 (04) :913-927
[3]   SIMULTANEOUS DETERMINATION OF A NOVEL ANTIARRHYTHMIC AGENT, 7-BENZYL-3-THIA-7-AZABICYCLO[3.3.1] NONANE AND ITS SULFOXIDATION METABOLITE IN PLASMA AND URINE BY HPLC [J].
CHEN, CL ;
SANGIAH, S ;
CHEN, H ;
BERLIN, KD ;
GARRISON, GL ;
SCHERLAG, BJ ;
LAZZARA, R .
JOURNAL OF LIQUID CHROMATOGRAPHY, 1994, 17 (17) :3681-3694
[4]   HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC DETERMINATION OF SAZ-VII-22, A NOVEL ANTIARRHYTHMIC AGENT, IN DOG PLASMA AND URINE [J].
CHEN, CL ;
RODER, JD ;
SANGIAH, S ;
CHEN, H ;
BERLIN, KD ;
GARRISON, GL ;
SCHERLAG, BJ ;
LAZZARA, R ;
PATTERSON, E .
ANALYTICAL SCIENCES, 1993, 9 (03) :429-431
[5]   HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC DETERMINATION OF SAZ-VII-23, A NOVEL ANTIARRHYTHMIC AGENT, IN DOG PLASMA AND URINE [J].
CHEN, CL ;
RODER, JD ;
SANGIAH, S ;
CHEN, H ;
BERLIN, KD ;
GARRISON, GL ;
SCHERLAG, BJ ;
LAZZARA, R ;
PATTERSON, E .
ANALYTICAL LETTERS, 1993, 26 (06) :1125-1135
[6]  
*COMP ASS INC INC, US GUID WINN CA CRIC
[7]   Inhibition of GTP gamma S-dependent phospholipase D and Rho membrane association by calphostin is independent of protein kinase C catalytic activity [J].
Dubyak, GR ;
Kertesy, SB .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1997, 341 (01) :129-139
[8]  
FABBRI M, 1994, J BIOL CHEM, V269, P26848
[9]   CALPHOSTIN-C STIMULATES EPIDERMAL GROWTH-FACTOR RECEPTOR PHOSPHORYLATION AND INTERNALIZATION VIA LIGHT-DEPENDENT MECHANISM [J].
GAMOU, S ;
SHIMIZU, N .
JOURNAL OF CELLULAR PHYSIOLOGY, 1994, 158 (01) :151-159
[10]  
Gaynon PS, 1997, CANCER-AM CANCER SOC, V80, P1717, DOI 10.1002/(SICI)1097-0142(19971101)80:9<1717::AID-CNCR4>3.0.CO