Improved assay for R(−)-apomorphine with application to clinical pharmacokinetic studies in Parkinson's disease

Ingram, Wendy M.; Priston, M. J.; Sewell, Graham

doi:10.1016/j.jchromb.2005.11.005

Cited by 10 publications

(8 citation statements)

References 18 publications

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“…As we know, HPLC and GC coupled with various detectors are powerful techniques for the analysis of compounds from complex matrices because their high capacity of separation and detection. In the previous studies, APO was separated by HPLC and detected by UV, fluorimetric and electrochemical detections 11–22. Among these previous studies, the highest sensitivity was achieved by using electrochemical detection with a LOD of 0.08 ng/mL 16.…”

Section: Resultsmentioning

confidence: 99%

“…High‐performance liquid chromatography (HPLC) coupled with different detectors including fluorimetric,11–13 UV,14, 15 and electrochemical16–22 detectors has been extensively adopted for determining APO in biological fluids. 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.…”

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confidence: 99%

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

Yang

Zhu

Deng

et al. 2006

Rapid Comm Mass Spectrometry

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A sensitive, rapid and specific quantitative liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and validated for the determination of apomorphine (APO) in canine plasma. The analytes were prepared using one-step liquid-liquid extraction, and analyzed on a Waters Symmetry C(18) column interfaced with triple quadrupole tandem mass spectrometer. A mixture of methanol/0.1% formic acid in water (70: 30, v/v) was employed as the isocratic mobile phase. Positive electrospray ionization was utilized as the ionization source. The analyte and clenbuterol (internal standard) were both detected using multiple reaction monitoring (MRM) mode. The limit of detection (LOD) obtained was 0.03 ng/mL. The assay was linear over the concentration range of 0.1-100 ng/mL, and provided good precision (RSD) and good accuracy (RE). The analyte was stable by using antioxidants throughout the whole study. The experimental results show that LC/MS/MS is a rapid and sensitive method to analyze APO in plasma. Finally, the proposed method was successfully applied to a pharmacokinetic study of APO after intranasal administration of 0.5 mg apomorphine to 10 healthy beagle dogs.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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

Yang

Zhu

Deng

et al. 2006

Rapid Comm Mass Spectrometry

View full text Add to dashboard Cite

show abstract

“…One of the difficulties with apomorphine administration is its inherent instability 3, 24. Auto‐oxidation of apomorphine to quinone species is a potentially important factor in apomorphine metabolism 25. Moreover, internal conversion from the R to the S form at physiological pH values is another concern 4.…”

Section: Discussionmentioning

confidence: 99%

Development and Evaluation of Perfluorocarbon Nanobubbles for Apomorphine Delivery

Hwang

Lin

Chi

et al. 2009

Journal of Pharmaceutical Sciences

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“…The specificity/stability indicating assay was modified from the procedures of earlier studies by Priston and Sewell 11 and Ingram et al 12 There were two sets of samples consisting of 2.5 mL of (100 μg/mL) apomorphine HCl solutions which included: 1) 1 mL of 0.1 M NaOH; 2) 1 mL of 0.1 M HCl; 3) 1 mL of 6% H 2 O 2 ; and 4) 1 mL of water (as control), respectively. Each sample was diluted to 5 mL with water, sealed in a volumetric flask and incubated at 25°C (water bath), and analyzed after 10 and 60 minutes’ exposure.…”

Section: Methodsmentioning

confidence: 99%

Stability of apomorphine in solutions containing selected antioxidant agents

Ang¹,

Boddy²,

Liu³

et al. 2016

DDDT

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Apomorphine in solution undergoes rapid autoxidation, producing greenish colored solutions, making it difficult to formulate as a stable pharmaceutical solution. To identify the optimum antioxidant agent/combination for apomorphine solution, a high performance liquid chromatography assay was used to study the stability of 50 μg/mL apomorphine HCI in 0.1% L-ascorbic acid (AA), 0.1% sodium metabisulfite (SMB), 0.1% EDTA, and in selected combinations at 25°C, 32°C, and 37°C over a period of 14 days. The stability of apomorphine HCl (10 mg/mL) in 0.1% AA solution and in 0.1% EDTA solution at 25°C and 37°C was also evaluated. Apomorphine HCI solution (50 μg/mL) in 0.1% AA plus 0.1% SMB solution retained 99.7% (at 25°C) and 95.9% (at 37°C) of the initial concentration, as 0.1% AA plus SMB solution minimized the reactive oxygen content in solution which, in turn, reduced the oxidation rate of apomorphine HCl, and there was no green coloration perceptible. Conversely, apomorphine HCl solution (50 μg/mL) in 0.1% SMB solution was unstable as only 0.53% (at 25°C) and 0.06% (at 37°C) of the initial concentration was retained after 14 days. All 10 mg/mL apomorphine HCl samples were stable in both studies. The initial concentration of apomorphine HCl solution markedly affected its rate of oxidation and discoloration. The addition of 0.1% AA to a current formulation of apomorphine HCl injection (Apomine®), which contains SMB as an antioxidant, was recommended as providing the most stable solution.

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Improved assay for R(−)-apomorphine with application to clinical pharmacokinetic studies in Parkinson's disease

Cited by 10 publications

References 18 publications

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

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

Development and Evaluation of Perfluorocarbon Nanobubbles for Apomorphine Delivery

Stability of apomorphine in solutions containing selected antioxidant agents

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