Differential pharmacokinetics and the brain distribution of morphine and ephedrine constitutional isomers in rats after oral administration with Keke capsule using rapid‐resolution LC–MS/MS

• Published in: Journal of separation science Vol. 37; no. 4; pp. 352 - 359
• Main Authors: Song, Yonggui, Su, Dan, Lu, Tulin, Mao, Chunqin, Ji, De, Liu, Yali, Wei, Binbin, Fan, Ronghua
• Format: Journal Article
• Language: English
• Published: Weinheim Blackwell Publishing Ltd 01.02.2014; Wiley; Wiley Subscription Services, Inc
• Subjects: active ingredients; Administration, Oral; adverse effects; Alkaloids; Animals; Biological and medical sciences; Brain; Central nervous system; Chromatography; Chromatography, High Pressure Liquid; Cough; Ephedrine; Ephedrine - administration & dosage; Ephedrine - chemistry; Ephedrine - pharmacokinetics; General pharmacology; Isomers; Keke capsule; Kinetics; Male; Mass spectrometry; Medical sciences; Molecular Conformation; Morphine; Morphine - administration & dosage; Morphine - chemistry; Morphine - pharmacokinetics; oral administration; Pharmacognosy. Homeopathy. Health food; Pharmacokinetics; Pharmacology; Pharmacology. Drug treatments; Pseudoephedrine; Rats; Rats, Wistar; Stereoisomerism; Tandem Mass Spectrometry; Tissue Distribution; Asia; China; Biological fluid; Tandem mass spectrometry; Agonist; Chemical analysis; Rat; Gnetales; Epimer; Ephedrine; Central nervous system; HPLC chromatography; Opiates; Morphine; Narcotic analgesic; Papaveraceae; Blood; β-Adrenergic receptor; Encephalon; Medicinal plant; Blood plasma; Tissue; Alkaloid; Pseudoephedrine; Folk medicine; Dicotyledones; Angiospermae; Gymnospermae; Vasoconstrictor agent; Quantitative analysis; Validation; Coupled method; Pharmacognosy; Bronchodilator; Rodentia; Oral administration; Sympathomimetic; Keke capsule; Papaver; Vertebrata; Reversed phase chromatography; Mammalia; α-Adrenergic receptor; Animal; Distribution; Plant origin; Nasal decongestant; Spermatophyta; α-Adrenergic receptor agonist; Pharmacokinetics
• ISSN: 1615-9306; 1615-9314
• DOI: 10.1002/jssc.201300886

Opioid and ephedra alkaloids known as the active ingredients for Keke capsule, which is used to treat coughs and bronchial asthma, could have potential adverse effects on the central nervous system. Therefore, an efficient, sensitive rapid‐resolution LC–MS/MS method for the simultaneous determination of morphine, ephedrine, and pseudoephedrine in rat plasma and brain tissue homogenate has been developed. The method was validated in the plasma and brain tissue samples, showed good linearity over a wide concentration range (r² > 0.99). The intra‐ and interday assay variability was less than 15% for all analytes, and the accuracy was between −8.8 and 5.7%. The study provided the pharmacokinetics profiles and the brain regional distribution of the three active alkaloids after oral administration of Keke capsule. The results also indicated that significant difference in pharmacokinetics parameters of the epimers was observed between ephedrine and pseudoephedrine.