The Application Of High-Performance Liquid Chromatography Coupled With Mass Spectrometry On Drug Analysis

HPLC/MS/MS technology is combining rapid separation capability of HPLC and high sensitivity, high specificity of MS, has been used as an analytical technique in drug analysis fields, such asdrug analysis in vivo, study of drug metabolism. This dissertation is to use HPLC/MS technology for quantitative analysis of specific drugs, by comparing different drugs to analysis the pharmacokinetic or evaluate the bioequivalence.To establish a method for determination of paracetamol and chlorphenamine maleate in human plasma by HPLC/MS. Method verification had been done successfully. The luna 5μm C18(2) column was used. A mixture of methanol and 0.4% acetic acid, 0.02% ammonium acetate in water (55:45, v/v), was used as the isocratic mobile phase. Ethyl acetate was chosed as the solvent of extraction. Under these conditions, HPLC/ESI/MS technology has successfully analyzed the concentration of paracetamol and chlorphenamine maleate in 20 healthy volunteers'plasma. By comparing the pharmacokinetic parameters of paracetamol and chlorphenamine maleate between two formulations, no significant difference has been found, so the two formulations have completely equivalence.Using LC/MS technology, L-carnitine (LC) and acetyl-L-carnitine (ALC) in human plasma or urine have been determined simultaneously. Determination of total carnitine (TC) in the samples required a simple procedure of hydrolyzation, in which the acylcarnitine was hydrolyzed to LC. Method validation shows it is sensitive and accurate. Sample processing method is simple, while greatly reduces the cost of applied research, as well as can be used to the large samples for analysis flux. The assay was successfully applied to the pharmacokinetic study after oral administration of acetyl-L-carnitine tablets to healthy volunteers.To determine domperidone concentrations in human plasma and study the relative bioavailability of domperidone tablets. The alkalinized sample was extracted by ethyl acetate. This method is sensitive, accurate and fast, has been successfully applied to the bioavailability study after oral administration of 10 mg domperidone tablets to 20 healthy volunteers. The results show that two different formulations have bioequivalent effect.By applying HPLC/MS/MS technology to analyze drug concentrations of the above mentioned some drugs in human plasma and urine, concentration-time curve was obtained. The bioequivalent effect of two formulations about paracetamol and chlorphenamine maleate and domperidone Capsules was evalued, it was successfully applied to the pharmacokinetic study about L-carnitine.