Analysis of pyridoquinoline derivatives by liquid chromatography/atmospheric pressure chemical ionization mass spectrometry

Abstract

A method using liquid chromatography/atmospheric pressure chemical ionization mass spectrometry (LC/APCI-MS) has been developed for the characterization and determination of pyridoquinoline derivatives 4,6-bis(dimethylaminoethylamino)-2,8,10-trimethylpyrido[3,2-g]quinoline, 4,6-bis(dimethylaminoethoxy)-2,8,10-trimethylpyrido[3,2-g]quinoline and 4,6-bis[(dimethylaminoethyl)thio]-2,8,10-trimethylpyrido[3,2-g] quinoline, all with potential antitumor properties. LC separation was performed on a conventional C18 column using a binary mobile phase composed of acetonitrile and 50 mM aqueous ammonium formate at pH 3. The APCI mass spectra obtained showed that proton addition giving [M + H]+ was the common mode of ionization to the amino- and thiopyridoquinolines, whereas the alkoxypyridoquinoline was identified by the main formation of the [M - (C2H3)N(CH3)2 + H]+, followed by the [M + H]+ ion. The LC separation conditions and MS detection parameters were optimized for the determination. The analytical method was also applied to the determination of these pyridoquinoline derivatives in fetal calf serum using liquid-liquid extraction with dichloromethane. Acceptable recovery values were obtained, ranging between 45 and 98%.

Liquid chromatography‐mass spectrometry for the quantitative bioanalysis of anticancer drugs

“…Topoisomerase I inhibitors are not necessarily camptothecin analogs. Picó and coworkers (2001) have reported on the quantitative analysis of three pyridoquinoline derivatives in bovine serum using LC‐HN‐APCI‐MS in the SIM mode and Wang et al (2002) describe the rapid and sensitive determination of an indolocarbazole in human plasma using LC‐MS/MS in negative ion mode. The pyridoquinoline derivatives amino‐, thio‐, and alkoxy‐pyridoquinoline were originally under development as antimalarial compounds and their antitumor, topoisomerase I inhibitory activity has been identified in vitro .…”

“…An assay with poor chromatography, resulting in bad peak shapes, is described, using rather large sample volumes. However, linearity, inter‐assay precision, and selectivity were good (Picó et al, 2001). For the extraction of indolocarbazole derivative I from plasma, an unusual procedure using solid–liquid extraction on diatomaceous earth plates was employed for sample pretreatment.…”

Determination of new pyridoquinoline derivatives and their quantification in urine by capillary liquid chromatography

“…For this reason there is a pressing need to develop analytical methods for their quantification and purity determination. Quinoline derivatives have mostly been separated and analyzed by high performance liquid chromatography (HPLC) [7,8] also in combination with mass spectrometry (MS) [9] and electrochemical detection [10]. Using reverse-phase HPLC, benzoquinolines were determined in waste water and atmosphere samples taken from an industrial area [11] and motor oil [12].…”