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Sensitive and rapid liquid chromatography/tandem mass spectrometric assay for the quantification of piperaquine in human plasma.

Abstract

A simple, sensitive and rapid liquid chromatography/tandem mass spectrometric (LC-MS/MS) method was developed and validated for quantification of piperaquine, an antimalarial drug, in human plasma using its structural analogue, piperazine bis chloroquinoline as internal standard (IS). The method involved a simple protein precipitation with methanol followed by rapid isocratic elution of analytes with 10mM ammonium acetate buffer/methanol/formic acid/ammonia solution (25/75/0.2/0.15, v/v) on Chromolith SpeedROD RP-18e reversed phase chromatographic column and quantification by mass spectrometry in the multiple reaction monitoring mode (MRM). The precursor to product ion transitions of m/z 535.3-->288.2 and m/z 409.1-->205.2 were used to measure the analyte and the IS, respectively. The assay exhibited a linear dynamic range of 1.0-250.2 ng/mL for piperaquine in plasma. The limit of detection (LOD) and lower limit of quantification (LLOQ) in plasma were 0.2 and 1.0 ng/mL, respectively. Acceptable precision and accuracy (+/-20% deviation for LLOQ standard and +/-15% deviation for other standards from the respective nominal concentration) were obtained for concentrations over the standard curve ranges. A run time of 2.5 min for a sample made it possible to achieve a throughput of more than 400 plasma samples analyzed per day. The validated method was successfully applied to analyze human plasma samples from phase-1 clinical studies. The mean pharmacokinetic parameters of piperaquine following 1000 mg oral dose: observed maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax) and elimination half-life (T1/2) were 46.1 ng/mL, 3.8h and 13 days, respectively.

Authors+Show Affiliations

Metabolism and Pharmacokinetic Department, Ranbaxy Research Laboratories, Plot # 20, Sector-18, Udhyog Vihar Industrial Area, Gurgaon, Haryana 122015, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

17923446

Citation

Singhal, Puran, et al. "Sensitive and Rapid Liquid Chromatography/tandem Mass Spectrometric Assay for the Quantification of Piperaquine in Human Plasma." Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, vol. 859, no. 1, 2007, pp. 24-9.
Singhal P, Gaur A, Gautam A, et al. Sensitive and rapid liquid chromatography/tandem mass spectrometric assay for the quantification of piperaquine in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;859(1):24-9.
Singhal, P., Gaur, A., Gautam, A., Varshney, B., Paliwal, J., & Batra, V. (2007). Sensitive and rapid liquid chromatography/tandem mass spectrometric assay for the quantification of piperaquine in human plasma. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 859(1), 24-9.
Singhal P, et al. Sensitive and Rapid Liquid Chromatography/tandem Mass Spectrometric Assay for the Quantification of Piperaquine in Human Plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Nov 1;859(1):24-9. PubMed PMID: 17923446.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sensitive and rapid liquid chromatography/tandem mass spectrometric assay for the quantification of piperaquine in human plasma. AU - Singhal,Puran, AU - Gaur,Ashwani, AU - Gautam,Anirudh, AU - Varshney,Brijesh, AU - Paliwal,Jyoti, AU - Batra,Vijay, Y1 - 2007/09/21/ PY - 2007/07/03/received PY - 2007/08/30/revised PY - 2007/09/02/accepted PY - 2007/10/10/pubmed PY - 2008/1/31/medline PY - 2007/10/10/entrez SP - 24 EP - 9 JF - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences JO - J Chromatogr B Analyt Technol Biomed Life Sci VL - 859 IS - 1 N2 - A simple, sensitive and rapid liquid chromatography/tandem mass spectrometric (LC-MS/MS) method was developed and validated for quantification of piperaquine, an antimalarial drug, in human plasma using its structural analogue, piperazine bis chloroquinoline as internal standard (IS). The method involved a simple protein precipitation with methanol followed by rapid isocratic elution of analytes with 10mM ammonium acetate buffer/methanol/formic acid/ammonia solution (25/75/0.2/0.15, v/v) on Chromolith SpeedROD RP-18e reversed phase chromatographic column and quantification by mass spectrometry in the multiple reaction monitoring mode (MRM). The precursor to product ion transitions of m/z 535.3-->288.2 and m/z 409.1-->205.2 were used to measure the analyte and the IS, respectively. The assay exhibited a linear dynamic range of 1.0-250.2 ng/mL for piperaquine in plasma. The limit of detection (LOD) and lower limit of quantification (LLOQ) in plasma were 0.2 and 1.0 ng/mL, respectively. Acceptable precision and accuracy (+/-20% deviation for LLOQ standard and +/-15% deviation for other standards from the respective nominal concentration) were obtained for concentrations over the standard curve ranges. A run time of 2.5 min for a sample made it possible to achieve a throughput of more than 400 plasma samples analyzed per day. The validated method was successfully applied to analyze human plasma samples from phase-1 clinical studies. The mean pharmacokinetic parameters of piperaquine following 1000 mg oral dose: observed maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax) and elimination half-life (T1/2) were 46.1 ng/mL, 3.8h and 13 days, respectively. SN - 1570-0232 UR - https://www.unboundmedicine.com/medline/citation/17923446/Sensitive_and_rapid_liquid_chromatography/tandem_mass_spectrometric_assay_for_the_quantification_of_piperaquine_in_human_plasma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1570-0232(07)00651-4 DB - PRIME DP - Unbound Medicine ER -