A sensitive and selective liquid chromatographic tandem mass spectrometric assay for simultaneous quantification of novel trioxane antimalarials in different biomatrices using sample-pooling approach for high throughput pharmacokinetic studies☆

Singh, Rajendra; Sabarinath, Sreedharan Nair; Singh, Shio Kumar; Gupta, R. C.

doi:10.1016/j.jchromb.2008.01.054

Cited by 13 publications

(8 citation statements)

References 22 publications

(18 reference statements)

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“…However, some authors only investigated the absolute matrix effect and did not evaluate the effect of matrices from different sources [31,[58][59][60][61][62][63][64][65][66][67][68]. Cao et al [62] have quantified methyl protodioscin, a natural furostanol saponin with antitumor activity, in rat plasma after PPT.…”

Section: Literature Overviewmentioning

confidence: 99%

Validation of bioanalytical LC–MS/MS assays: Evaluation of matrix effects

Eeckhaut

Lanckmans

Sarre

et al. 2009

Journal of Chromatography B

684

379

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Section: Literature Overviewmentioning

confidence: 99%

Validation of bioanalytical LC–MS/MS assays: Evaluation of matrix effects

Eeckhaut

Lanckmans

Sarre

et al. 2009

Journal of Chromatography B

684

379

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“…The assay method was adapted from a previously published work, where Singh, Sabarinath, Singh, and Gupta () developed and validated a method for quantification of 99/411 in plasma (rat, rabbit and monkey). Mass spectrometric detection was performed on an API 4000 mass spectrometer (Applied Biosystems, MDS Sciex Toronto, Canada) equipped with an electrospray ionization source and Perkin‐Elmer LC system (Perkin Elmer, USA).…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetic studies of a novel trioxane antimalarial (99/411) in rats and monkeys using LC–MS/MS

Pandey

Gautam

Kushwaha

et al. 2016

Biomedical Chromatography

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The pharmacokinetic profile of 99/411, a novel anti-malarial drug, was established in rats (12 mg/kg of body weight) and monkeys (20 mg/kg of body weight). Following oral administration, the presence of 99/411 was rapidly determined in rat plasma, tissues, urine, feces and monkey plasma using a validated LC-MS/MS method. The tissue distribution studies in rats indicated that the drug was partially distributed in all major tissues and plasma, and peak concentration levels were achieved within 0.5-4 h. Area under the curve in different rat tissues and plasma was found in order of blood > lung > intestine > heart > muscle > brain > kidney > spleen > liver. The total recoveries (within 86 h) of 99/411 were <0.0017% and <0.08% in urine and feces, respectively. The peak plasma concentration was 3499 ng/mL in rats after ~2 h of oral administration and 697-767 ng/mL in monkeys after ~6 h of oral administration. No plasma accumulation was observed in both male and female monkeys, even after multiple dosing. The preclinical pharmacokinetic profile and tissue distribution data are expected to assist in future clinical explorations of 99/411 as a promising anti-malarial agent.

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“…Selectivity,sensitivity,linearity,a ccuracy,precision werem easured and used ast he parameters tovalidate and assess the bioanalyticalassayperformance [12,13]. The most abundantion in the production spectraof ammoniumadductof parentdrug9 7-78( m/z =518.4), 97-63 and IS ass howni nTable 1.…”

Section: Methods Validationmentioning

confidence: 99%

Pharmacokinetic study of the novel, synthetic trioxane antimalarial compound 97-78 in rats using an LC-MS/MS method for quantification

Singh

Sabarinath

Gautam

et al. 2011

Arzneimittelforschung

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The present study has been designed to investigate the pharmacokinetic parameters of the novel trioxane antimalarial 97-78 (US Patent 6316493 B1, 2001) in male and female rats after single oral and intravenous administration. The pharmacokinetic profile of 97-78 was investigated in the form of its completely converted metabolite 97-63 after dose administration. Quantification of metabolite 97-63 in rat plasma was achieved using a simple and rapid LC-MS/MS method. The LC-MS/MS method has been validated in terms of accuracy, precision, sensitivity and recovery for metabolite 97-63 in rat plasma. The intra- and interday accuracy (% bias) and precision (% RSD) values of the assay were less than 10% for metabolite 97-63. The chromatographic run time was 4.0 min and the weighted (1/x2) calibration curves were linear over the range 1.56-200 ng/ml. This method was successfully applied for analysis of pharmacokinetic study samples. Maximum plasma concentrations of 97-63 at 47 mg/kg oral administration in male and female rats were 1986.6 ng/ml and 4086.7 ng/ml at time (Tmax) 0.92 h and 0.58 h, respectively. The area under the curve (AUC(0-infinity)), elimination half-life (t(1/2) beta) and mean residence time (MRT) were 4669.98 ng x h/ml, 2.8 h and 4.2 h in male and 11786.0 ng x h/ml, 4.52 h and 4.32 h in female rats respectively. After single oral and intravenous administration of 97-78 to male and female rats significant differences were observed in pharmacokinetic parameters (AUC and t (1/2) beta) for metabolite 97-63.

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A sensitive and selective liquid chromatographic tandem mass spectrometric assay for simultaneous quantification of novel trioxane antimalarials in different biomatrices using sample-pooling approach for high throughput pharmacokinetic studies☆

Cited by 13 publications

References 22 publications

Validation of bioanalytical LC–MS/MS assays: Evaluation of matrix effects

Validation of bioanalytical LC–MS/MS assays: Evaluation of matrix effects

Pharmacokinetic studies of a novel trioxane antimalarial (99/411) in rats and monkeys using LC–MS/MS

Pharmacokinetic study of the novel, synthetic trioxane antimalarial compound 97-78 in rats using an LC-MS/MS method for quantification

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