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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.
J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Mar 15; 864(1-2):52-60.JC

Abstract

In the present studies, to give momentum to traditionally low throughput pharmacokinetic screening, a bioanalytical method based on the concept of sample pooling for simultaneous bioanalysis of multiple compounds is discussed. A sensitive, selective, specific and rapid HPLC/ESI-MS/MS assay method was developed and validated for the simultaneous quantitation of three novel trioxane antimalarials (99-357, 99-408 and 99-411) in rat plasma using trioxane analogue as internal standard. The suitably validated bioanalytical method was then further extrapolated to rabbit and monkey plasma by performing partial validation. Extraction from the plasma involves a simple two-step liquid-liquid extraction with n-hexane. The analytes were chromatographed on a cyano column by isocratic elution with acetonitrile:ammonium acetate buffer (pH 6) (85:15, v/v) and analyzed by mass spectrometry in multiple reaction-monitoring (MRM) mode. The chromatographic run time was 5.5 min and the weighted (1/x(2)) calibration curves were linear over a range of 1.56-200 ng/ml. The limit of detection (LOD) and lower limit of quantification (LLOQ) in rat plasma, rabbit plasma and monkey plasma were 0.78 and 1.56 ng/ml, respectively, for all three analytes. The intra- and inter-batch accuracy and precision in terms of % bias and % relative standard deviation were found to be well within the acceptable limits (< 15%). The average absolute recoveries of 99-357, 99-408 and 99-411 from spiked plasma samples were > 90%, > 70% and > 60%, respectively. The assay method described here could be applied to study the pharmacokinetics of 99-357, 99-408 and 99-411 using sample-pooling technique.

Authors+Show Affiliations

Pharmacokinetics & Metabolism Division, Central Drug Research Institute, Lucknow 226001, India.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18316253

Citation

Singh, Rajendra Pratap, et al. "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." Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, vol. 864, no. 1-2, 2008, pp. 52-60.
Singh RP, Sabarinath S, Singh SK, et al. 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. J Chromatogr B Analyt Technol Biomed Life Sci. 2008;864(1-2):52-60.
Singh, R. P., Sabarinath, S., Singh, S. K., & Gupta, R. C. (2008). 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. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 864(1-2), 52-60. https://doi.org/10.1016/j.jchromb.2008.01.054
Singh RP, et al. 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. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Mar 15;864(1-2):52-60. PubMed PMID: 18316253.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Singh,Rajendra Pratap, AU - Sabarinath,S, AU - Singh,Shio Kumar, AU - Gupta,Ram Chandra, Y1 - 2008/02/17/ PY - 2007/10/03/received PY - 2008/01/18/revised PY - 2008/01/24/accepted PY - 2008/3/5/pubmed PY - 2008/6/6/medline PY - 2008/3/5/entrez SP - 52 EP - 60 JF - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences JO - J Chromatogr B Analyt Technol Biomed Life Sci VL - 864 IS - 1-2 N2 - In the present studies, to give momentum to traditionally low throughput pharmacokinetic screening, a bioanalytical method based on the concept of sample pooling for simultaneous bioanalysis of multiple compounds is discussed. A sensitive, selective, specific and rapid HPLC/ESI-MS/MS assay method was developed and validated for the simultaneous quantitation of three novel trioxane antimalarials (99-357, 99-408 and 99-411) in rat plasma using trioxane analogue as internal standard. The suitably validated bioanalytical method was then further extrapolated to rabbit and monkey plasma by performing partial validation. Extraction from the plasma involves a simple two-step liquid-liquid extraction with n-hexane. The analytes were chromatographed on a cyano column by isocratic elution with acetonitrile:ammonium acetate buffer (pH 6) (85:15, v/v) and analyzed by mass spectrometry in multiple reaction-monitoring (MRM) mode. The chromatographic run time was 5.5 min and the weighted (1/x(2)) calibration curves were linear over a range of 1.56-200 ng/ml. The limit of detection (LOD) and lower limit of quantification (LLOQ) in rat plasma, rabbit plasma and monkey plasma were 0.78 and 1.56 ng/ml, respectively, for all three analytes. The intra- and inter-batch accuracy and precision in terms of % bias and % relative standard deviation were found to be well within the acceptable limits (< 15%). The average absolute recoveries of 99-357, 99-408 and 99-411 from spiked plasma samples were > 90%, > 70% and > 60%, respectively. The assay method described here could be applied to study the pharmacokinetics of 99-357, 99-408 and 99-411 using sample-pooling technique. SN - 1570-0232 UR - https://www.unboundmedicine.com/medline/citation/18316253/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_ DB - PRIME DP - Unbound Medicine ER -