Tags

Type your tag names separated by a space and hit enter

Development and validation of a rapid, sensitive liquid chromatography-tandem mass spectrometry method using electrospray ionization for quantitation of centchroman in rat plasma and its application to preclinical pharmacokinetic study.

Abstract

A highly sensitive and specific HPLC-ESI-MS/MS method has been developed and validated for the estimation of centchroman with 100 microL rat plasma using tamoxifen as an internal standard (IS). The assay procedure involved a single-step, liquid-liquid extraction of centchroman and IS from plasma with 2.5% (v/v) isopropanol in n-hexane, which yielded consistent recoveries of 109.5 and 107.8% for centchroman and IS in rat plasma, respectively. The total chromatographic run time was 3.8 min. Peaks were resolved using 0.01 M ammonium acetate (pH 4.5):acetonitrile (10:90, v/v) mobile phase on a Supelco Discovery C(18) column. Specificity and matrix effect on ionization was determined and found that method was specific and there was no significant matrix effect. Linearity range was found to be 0.5-100.0 ng/mL with a correlation coefficient (r) of 0.9959 or better. The intra- and inter-day assay precision ranged from 3.3 to 9.0% and 5.5 to 6.8%, respectively, and intra- and inter-day assay accuracy was between 93.4-107.1% and 96.2-104.2%, respectively. Stability of centchroman in rat plasma was >89.0% in the battery of stability studies viz., bench-top, auto-sampler, freeze/thaw cycles and 30 days storage in a freezer at -80 degrees C. The assay was successfully applied to determine the pharmacokinetic parameters in Sprague-Dawley rats after an oral administration of centchroman at 20mg/kg. As a result, the plasma half-life was 29.4+/-2.3h and the AUC((0-infinity)) was 7345.1+/-21.9 ng h/mL. The maximum plasma concentration (C(max)) 117.5+/-15.7 ng/mL was achieved at 9.0+/-8.6h (t(max)).

Authors+Show Affiliations

Pharmacokinetics and Metabolism Division, Central Drug Research Institute, Lucknow, Uttar Pradesh, India.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Validation Study

Language

eng

PubMed ID

19004674

Citation

Singh, Sheelendra Pratap, et al. "Development and Validation of a Rapid, Sensitive Liquid Chromatography-tandem Mass Spectrometry Method Using Electrospray Ionization for Quantitation of Centchroman in Rat Plasma and Its Application to Preclinical Pharmacokinetic Study." Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, vol. 876, no. 1, 2008, pp. 1-7.
Singh SP, Singh RS, Wahajuddin , et al. Development and validation of a rapid, sensitive liquid chromatography-tandem mass spectrometry method using electrospray ionization for quantitation of centchroman in rat plasma and its application to preclinical pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci. 2008;876(1):1-7.
Singh, S. P., Singh, R. S., Wahajuddin, ., & Jain, G. K. (2008). Development and validation of a rapid, sensitive liquid chromatography-tandem mass spectrometry method using electrospray ionization for quantitation of centchroman in rat plasma and its application to preclinical pharmacokinetic study. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 876(1), 1-7. https://doi.org/10.1016/j.jchromb.2008.09.039
Singh SP, et al. Development and Validation of a Rapid, Sensitive Liquid Chromatography-tandem Mass Spectrometry Method Using Electrospray Ionization for Quantitation of Centchroman in Rat Plasma and Its Application to Preclinical Pharmacokinetic Study. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Dec 1;876(1):1-7. PubMed PMID: 19004674.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Development and validation of a rapid, sensitive liquid chromatography-tandem mass spectrometry method using electrospray ionization for quantitation of centchroman in rat plasma and its application to preclinical pharmacokinetic study. AU - Singh,Sheelendra Pratap, AU - Singh,Ravi Shankar Prasad, AU - Wahajuddin,, AU - Jain,Girish Kumar, Y1 - 2008/10/14/ PY - 2008/08/06/received PY - 2008/09/23/revised PY - 2008/09/26/accepted PY - 2008/11/14/pubmed PY - 2009/2/20/medline PY - 2008/11/14/entrez SP - 1 EP - 7 JF - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences JO - J Chromatogr B Analyt Technol Biomed Life Sci VL - 876 IS - 1 N2 - A highly sensitive and specific HPLC-ESI-MS/MS method has been developed and validated for the estimation of centchroman with 100 microL rat plasma using tamoxifen as an internal standard (IS). The assay procedure involved a single-step, liquid-liquid extraction of centchroman and IS from plasma with 2.5% (v/v) isopropanol in n-hexane, which yielded consistent recoveries of 109.5 and 107.8% for centchroman and IS in rat plasma, respectively. The total chromatographic run time was 3.8 min. Peaks were resolved using 0.01 M ammonium acetate (pH 4.5):acetonitrile (10:90, v/v) mobile phase on a Supelco Discovery C(18) column. Specificity and matrix effect on ionization was determined and found that method was specific and there was no significant matrix effect. Linearity range was found to be 0.5-100.0 ng/mL with a correlation coefficient (r) of 0.9959 or better. The intra- and inter-day assay precision ranged from 3.3 to 9.0% and 5.5 to 6.8%, respectively, and intra- and inter-day assay accuracy was between 93.4-107.1% and 96.2-104.2%, respectively. Stability of centchroman in rat plasma was >89.0% in the battery of stability studies viz., bench-top, auto-sampler, freeze/thaw cycles and 30 days storage in a freezer at -80 degrees C. The assay was successfully applied to determine the pharmacokinetic parameters in Sprague-Dawley rats after an oral administration of centchroman at 20mg/kg. As a result, the plasma half-life was 29.4+/-2.3h and the AUC((0-infinity)) was 7345.1+/-21.9 ng h/mL. The maximum plasma concentration (C(max)) 117.5+/-15.7 ng/mL was achieved at 9.0+/-8.6h (t(max)). SN - 1570-0232 UR - https://www.unboundmedicine.com/medline/citation/19004674/Development_and_validation_of_a_rapid_sensitive_liquid_chromatography_tandem_mass_spectrometry_method_using_electrospray_ionization_for_quantitation_of_centchroman_in_rat_plasma_and_its_application_to_preclinical_pharmacokinetic_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1570-0232(08)00728-9 DB - PRIME DP - Unbound Medicine ER -