Determination of Submicrogram Quantities of Clonidine in Biological Fluids

Chu, L.‐C.; Bayne, W.F.; Tao, F.T.; Schmitt, Leonore G.; Shaw, Jane E.

doi:10.1002/jps.2600680122

Cited by 24 publications

(8 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numerous analytical methods, including radioimmunoassay (Arndts et al, 1981), HPLC (Rosansky et al, 1993), GC (Chu et al, 1979;Edlund, 1980;Nazarali et al, 1986;Velasquez et al, 1983), GC/MS (Arrendale et al, 1988;Girault and Fourtillan, 1988;Murray et al, 1981;Murray and Davies, 1984;Wenzl et al, 2002;Yamahata et al, 1994), LC-MS (Ke et al, 2004) and LC-MS/MS (Muller et al, 2007;Naidong et al, 2002) have been reported in the literature to quantify clonidine in biological fluids. None of these methods could reliably quantify clonidine concentration lower than 50 pg/ mL.…”

Section: Introductionmentioning

confidence: 98%

Liquid chromatography tandem mass spectrometry method for the quantification of clonidine with LLOQ of 10 pg/mL in human plasma

Nirogi

Kandikere

Mudigonda

et al. 2008

Biomedical Chromatography

View full text Add to dashboard Cite

A sensitive high-performance liquid chromatography-positive ion electrospray tandem mass spectrometry method was developed and validated for the quantification of clonidine in human plasma. Following liquid-liquid extraction, the analytes were separated using an isocratic mobile phase on a reverse-phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective [M + H](+) ions, m/z 230 to 44 for clonidine and m/z 254 to 44 for the internal standard. The assay exhibited a linear dynamic range of 10-2000 pg/mL for clonidine in human plasma. The lower limit of quantification was 10 pg/mL with a relative standard deviation of less than 6.8%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 2.5 min for each sample made it possible to analyze more than 250 human plasma samples per day. The validated method was successfully used to analyze human plasma samples for application in pharmacokinetic studies.

show abstract

Section: Introductionmentioning

confidence: 98%

Liquid chromatography tandem mass spectrometry method for the quantification of clonidine with LLOQ of 10 pg/mL in human plasma

Nirogi

Kandikere

Mudigonda

et al. 2008

Biomedical Chromatography

View full text Add to dashboard Cite

show abstract

“…Chu et al [17], Intraday variation, expressed as coefficient of variation in percent for successive analyses was 7.1 and 11.4% for clonidine at tissue concentrations of 7.9 and 2.9 ng/g (weight/weight; n = 6). The sensitivity of (he method was estimated to be about 10 pg of clonidine per injection.…”

Section: Determinations O F Concentrations O F Clonidine In Wholementioning

confidence: 99%

Hypothalamic Neurochemistry and Feeding Behavioral Responses to Clonidine, an Alpha-2-Agonist, and to Trifluoromethylphenylpiperazine, a Putative 5-Hydroxytryptamine-1B Agonist, in Genetically Obese Zucker Rats

et al. 1990

View full text Add to dashboard Cite

Genetically obese Zucker rats are hyperphagic, hyperinsulinemic and hyperlipemic. In order to investigate pathophysiological mechanisms underlying hyperphagia in these animals, monoamine metabolism and turnover were studied in discrete hypothalamic nuclei known to participate in the control of feeding behavior. Neurochemical studies in genetically obese Zucker rats and in their lean littermate controls were complemented by investigating feeding behavioral responses to the acute administration of clonidine (15 and 30 µg/kg i.p.), an α₂-adrenoceptor agonist, and to trifluoromethylphenylpiperazine (TFMPP; 1, 2 and 5 mg/kg s.c), a putative serotonergic 5-hydroxytryptamine-1B receptor agonist. Obese Zucker rats had significantly lower concentrations of 5-hydroxyindoleacetic acid, the main deaminated metabolite of 5-hydroxytryptamine, in the nucleus paraventricularis (PVN) and in the nucleus ventromedialis (VMN), when compared to their lean littermate controls. The rate of accumulation of 5-hydroxytryptophan after decarboxylase inhibition was reduced in the PVN, nucleus supraopticus, nucleus periventricularis and nucleus suprachiasmaticus of the obese rats. No differences were observed in basal concentrations of norepinephrine, dopamine or 3,4-dihydroxyphenylacetic acid between obese and lean Zucker rats in the brain areas studied. However, the rate of accumulation of 3,4-dihydroxyphenylalanine was lower in the VMN and in the median eminence of the obese rats. The feeding behavioral tests showed significantly augmented hyperphagic responses to clonidine in obese Zucker rats. The anorexic effect of TFMPP was similar in both phenotypes. It is concluded that serotonergic activity is reduced in obese Zucker rats, particularly in the PVN, which plays a key role in the control of feeding behavior. The reduced serotonergic activity may be associated with enhanced α₂-adrenoceptor-mediated feeding responses in obese Zucker rats. Both of these factors may play important roles in the development of hyperphagia and genetically determined obesity in these rats.

show abstract

“…Clonidine has been in clinical use for over 40 years, which is used to treat hypertensive disorders, hyperactivity disorder, anxiety disorders, migraine, menopausal flushing and certain pain conditions (Neil, 2011). Published methods have been used for the determination of clonidine, including HPLC (Rosansky et al, 1993), LC-MS/MS (Zhao et al, 2006;Muller et al, 2007;Parekh et al, 2008;Ghosh et al, 2009;Li et al, 2011), GC (Velasquez et al, 1983;Nazarali et al, 1986;Chu et al, 1979), GC-MS (Arrendale et al, 1988;Girault et al, 1988;Yamahata et al, 1994) and CE (Hercegová, 1998;Filipic et al, 2013). Hence a transdermal patch formulation of clonidine was developed (MacGregor et al,1985) to maintain clonidine plasma concentration in a steady state over a prolonged period of time and reduce the risk of adverse effects.…”

Section: Introductionmentioning

confidence: 99%

“…Then a sensitive and reliable analytical method needed to be established to describe the pharmacokinetic properties of transdermal clonidine patches in clinical trials thoroughly. In addition, clonidine was administered orally in all in vivo pharmacokinetic experiments (Chu et al, 1979;Velasquez et al, 1983;Muller et al, 2007;Li et al, 2011;Larsson et al, 2011), but there was little information related to the pharmacokinetic study after transdermal administration (Fujimura et al, 1994;Yamahata et al, 1994). Muller et al (2007) developed an LC-MS/MS method in human serum with a lower limit of quantitation (LLOQ) of 0.1 ng/mL while Li et al (2011) developed a 2D strong cation exchange reversed-phase LC-MS/MS method in dried blood spots with an LLOQ of 0.1 ng/mL.…”

Section: Introductionmentioning

confidence: 99%

“…Then a sensitive and reliable analytical method needed to be established to describe the pharmacokinetic properties of transdermal clonidine patches in clinical trials thoroughly. Published methods have been used for the determination of clonidine, including HPLC (Rosansky et al, 1993), LC-MS/MS (Zhao et al, 2006;Muller et al, 2007;Parekh et al, 2008;Ghosh et al, 2009;Li et al, 2011), GC (Velasquez et al, 1983;Nazarali et al, 1986;Chu et al, 1979), GC-MS (Arrendale et al, 1988;Girault et al, 1988;Yamahata et al, 1994) and CE (Hercegová, 1998;Filipic et al, 2013). Muller et al (2007) developed an LC-MS/MS method in human serum with a lower limit of quantitation (LLOQ) of 0.1 ng/mL while Li et al (2011) developed a 2D strong cation exchange reversed-phase LC-MS/MS method in dried blood spots with an LLOQ of 0.1 ng/mL.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Validation of a HPLC‐ESI MS/MS method for the determination of clonidine in human plasma and its application in a bioequivalence study in Chinese healthy volunteers

Liu

Chen

Wang

et al. 2015

Biomedical Chromatography

View full text Add to dashboard Cite

A rapid and sensitive liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method to determine clonidine in human plasma was developed and fully validated. Sample preparation was involved an one-step extraction with diethyl ether. Donepezil was employed as the internal standard (IS). Chromatographic separation was performed on a Hypersil BDS C18 column (i.d. 2.1 × 50 mm, particle size 3μm) with a mobile phase of methanol-water (containing 0.1% formic acid; 60:40, v/v) at a flow rate of 200 μL/min. The peaks were detected by mass spectrometry using the electrospray ion source in selected reaction monitoring mode. The extraction recovery was 72.53-85.25%. The method was found to be linear in a concentration range of 0.02-6.00 ng/mL and the lower limit of quantification was 0.02 ng/mL. The within- and between-batch precisions at three concentrations were 4.33-16.47 and 7.24-17.24% with accuracies of -2.47-10.91 and 1.86-10.19%, respectively. This validated method was successfully used for a bioequivalence study of two clonidine transdermal patches on healthy volunteers. The results suggested that the test formulation of clonidine patch met the regulatory criterion for bioequivalence to the reference formulation, but a larger sample size should be needed for the estimation of bioequivalence.

show abstract

Determination of Submicrogram Quantities of Clonidine in Biological Fluids

Cited by 24 publications

References 6 publications

Liquid chromatography tandem mass spectrometry method for the quantification of clonidine with LLOQ of 10 pg/mL in human plasma

Liquid chromatography tandem mass spectrometry method for the quantification of clonidine with LLOQ of 10 pg/mL in human plasma

Hypothalamic Neurochemistry and Feeding Behavioral Responses to Clonidine, an Alpha-2-Agonist, and to Trifluoromethylphenylpiperazine, a Putative 5-Hydroxytryptamine-1B Agonist, in Genetically Obese Zucker Rats

Validation of a HPLC‐ESI MS/MS method for the determination of clonidine in human plasma and its application in a bioequivalence study in Chinese healthy volunteers

Contact Info

Product

Resources

About