Pharmacokinetic studies, quantitative mass spectrometry

QUANTITATIVE MASS SPECTROMETRY IN SUPPORT OF PHARMACOKINETIC STUDIES... 

QUANTITATIVE MASS SPECTROMETRY IN SUPPORT OF PHARMACOKINETIC STUDIES TABLE 7.1 Precision and Accnracy of QC Sample Results (Robavirin)... 

A sensitive, simple, and specific liquid chromatographic method coupled with electrospray ionization-mass spectrometry for the determination of donepezil in plasma was developed, and its pharmacokinetics in healthy, male, Chinese was studied [34]. Using loratadine as the IS, after extraction of the alkalized plasma by isopropyl alcohol-n-hexane (3 97, v/v), solutes are separated on a Cig column with a mobile phase of methanol-acetate buffer (pH 4.0) (80 20, v/v). Detection is performed with a TOF mass spectrometer equipped with an electrospray ionization source operated in the positive-ionization mode. Quantitation of donepezil is accomplished by computing the peak area ratio (donepezil [M + H](+) m/z 380-loratadine [M + H](+) mlz 383) and comparing them with the calibration curve (r = 0.9998). The linear calibration curve is obtained in the concentration range 0.1-15 ng/ml. The limit of quantitation is 0.1 ng/ml. The mean recovery of donepezil from human plasma is 99.4 6.3% (range 93.4-102.6%). The inter- and intra-day RSD is less than 15%. After an oral administration of 5 mg donepezil to 20 healthy Chinese volunteers, the main pharmacokinetic parameters of donepezil are as follow T(max), 3.10 0.55 h tV2j 65.7 12.8 h C(max), 10.1 2.02 ng/ml MRT,... 

Macek et al. [120] developed a method to quantitate omeprazole in human plasma using liquid chromatography-tandem mass spectrometry. The method is based on the protein precipitation with acetonitrile and a reversed-phase liquid chromatography performed on an octadecylsilica column (55 x 2 mm, 3 /im). The mobile phase consisted of methanol-10 mM ammonium acetate (60 40). Omeprazole and the internal standard, flunitra-zepam, elute at 0.80 0.1 min with a total rim time 1.35 min. Quantification was through positive-ion made and selected reaction monitoring mode at m/z 346.1 —> 197.9 for omeprazole and m/z 314 —> 268 for flunitrazepam, respectively. The lower limit of quantification was 1.2 ng/ml using 0.25 ml of plasma and linearity was observed from 1.2 to 1200 ng/ml. The method was applied to the analysis of samples from a pharmacokinetic study. 

Segura M, Ortuno J, Farre M et al (2003) Quantitative determination of paroxetine and its 4-hydroxy-3-methoxy metabolite in plasma by high-performance liquid chromatography/elec-trospray ion trap mass spectrometry application to pharmacokinetic studies. Rapid Commun Mass Spectrom 17 1455-1461... 

Recent advances in mass spectrometry have rendered it an attractive and versatile tool in industrial and academic research laboratories. As a part of this rapid growth, a considerable body of hterature has been devoted to the apph-cation of mass spectrometry in clinical studies. In concert with separation techniques such as hquid chromatography, mass spectrometry allows the rapid characterization and quantitative determination of a large array of molecules in complex mixtures. Herein, we present an overview of the above techniques accompanied with several examples of the use of liquid chromatography-tandem mass spectrometry in pharmacokinetics/drug metabohsm assessment during drug development. 

Sanders, M. Josephs, J.L. Wang, J. Phillips, J.J. Mylchreest, 1. Highly Automated Process for the Quantitation of Samples from Animal Pharmacokinetic Studies using a Linear Ion Trap Mass Spectrometer, in Proceedings ofthe 51st ASMS Conference on Mass Spectrometry and Allied Topics, Montreal, Canada, June 8-12, 2003. 

W Muck. Quantitative analysis of pharmacokinetic study samples by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Pharmazie 54 639-644, 1999. 

A sensitive method for quantitation of glimepiride in human plasma was established using electrospray ionization tandem mass spectrometry (ESI/MS/MS). Detection of glimepiride is accurate and precise with a quantitation limit of 0.1 ng/ml. This method was successfully applied to a pharmacokinetic study of glimepiride. No interferences of the analytes were observed because of high selectivity of the MS/MS technique. The method of Song et al. is also sufficiently sensitive, with a quantification limit lower than the minimum concentration recommended for plasma samples obtained after the administration of 2 mg glimepiride. This smdy indicates a reliable stability of... 

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