Development of a gas chromatographic/mass spectrometric method to quantify R(–)‐apomorphine, R(–)‐apocodeine and R(–)‐norapomorphine in human plasma and urine

Abstract

A method was developed and validated for the analysis of R(-)-apomorphine, (R-)-apocodeine and R(-)-norapomorphine in human plasma and urine with N-propylnorapomorphine as internal standard using gas chromatography/mass spectrometry (GC/MS) and single-ion monitoring after a single liquid-liquid extraction and silylation of compounds. The quantification limits were 1 ng/ml for apomorphine and apocodeine and 25 ng/ml for norapomorphine. Calibration curves were linear, within the range 1-100 ng/ml. Variation in intraday and interday precision was below 10%. This method was applied to study apomorphine bioavailability in nine patients with Parkinson's disease before and after coadministration of a catechol-O-methyl transferase inhibitor.

Structural Characterisation of Alkaloids in Leaves and Roots of Stephania kwangsiensis by LC‐QTOF‐MS

“…S2) were assigned as aporphine alkaloids without N ‐methyl groups according to the [M + H–NH 3 ] + ions. Compound 19 possessed vicinal hydroxy groups based on the ions [M + H−NH 3 −H 2 O] + at m/z 219.0813 and [M + H−NH 3 −H 2 O−CO] + at m/z 191.0861, and was tentatively identified as norapomorphine (Libert et al ., ). Compound 25 had vicinal methoxy and hydroxy groups based on the [M + H−NH 3 −CH 3 OH] + at m/z 219.0808 and [M + H−NH 3 −CH 3 OH−CO] + at m/z 191.0856 fragments, and was tentatively deduced as asimilobine previously isolated from Stephania species (Semwal et al ., ).…”

Development of a sensitive and rapid liquid chromatography/tandem mass spectrometry method for the determination of apomorphine in canine plasma

“…The reported LC/MS method for the determination of APO in medicines achieved a LOD of 20 ng/mL 27. The lately developed GC/MS method for the determination of APO after silylation involves a time‐consuming derivatization step prior to analysis, with a LOD of 1 ng/mL 25. In our study, LOD is 0.03 ng/mL and the whole analytical procedure can be completed in a short run time (2.5 min), ensuring the high throughout and sensitivity required in PK studies.…”

“…However, these HPLC methods required relatively long chromatographic times (usually more than 10 min) to complete a whole analytical procedure; as a result, these methods could not satisfy the high throughout required in PK studies. Gas chromatography (GC) or gas chromatography/mass spectrometry (GC/MS) methods were also developed for quantification of APO in biological samples 23–25. However, since GC or GC/MS methods require precolumn derivatization procedures to convert APO into volatile derivatives prior to analysis, they are inconvenient and time‐consuming for PK studies.…”

Determination of apomorphine in canine plasma by liquid chromatography–electrospray ionization mass spectrometry and its application to a pharmacokinetic study

“…Among these studies, the lower LOD obtained were 0.5 and 0.67 ng/mL by using electrochemical detection [10,11]. The lately developed GC-MS method for the determination of apomorphine has to undergo a derivatization step prior to analysis [17], which is time-consuming and complex. In this study, LOQ is 0.4 ng/mL and the whole analytical procedure can be completed in a short time (5 min).…”

“…1. A review of the literature revealed that several analytical techniques have been developed for the quantification of apomorphine in biological samples, including GC [5], radioenzymatic assay [6], HPLC with UV [7], fluorimetric [8], and particularly electrochemical detection [9 -15]. A flow injection electrochemical method (FIA-EC) and a GC-MS method was also reported for the assay of apomorphine [16,17].…”