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

Abstract

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 (r(2) > 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.

Quantitative analysis and pharmacokinetics study of tigecycline in human serum using a validated sensitive liquid chromatography with tandem mass spectrometry method

“…In response, rational tigecycline use is proposed to prevent an escalation in antimicrobial resistance and maximize the likelihood of a favorable clinical response, as well as to minimize the probability of exposure‐related toxicity. It is now well recognized that the intrinsic pharmacokinetic (PK) and pharmacodynamic (PD) properties of the drug must be considered in order to achieve optimal clinical and microbiological outcomes . Prior to the establishment of tigecycline PK/PD model, a rapid and sensitive method for the analysis of tigecycline in human serum is necessarily demanded.…”

Multi‐component profiles through the blood–brain barrier in rat after oral administration of over‐the‐counter drug Keke capsule by ultra‐performance liquid chromatography/quadrupole‐ time‐of‐flight MSE method

“…At the same time, pseudoephedrine has an auxiliary function (Ze, Qian, & Yang, ). Compared with the previous reports (Song et al, ), this study shows simultaneous high‐throughput analysis of the main components in KC and detects the corresponding bioactive components and their distribution in the brain through BBB in the rat after oral administration of KC, so that a rapid, overall evaluation method has been devised. A rapid and overall method was formed for evaluation of the components in vitro and corresponding bioactive components absorbed into the blood and brain in the rat after oral administration of KC.…”

“…Adopting a simple method for sample treatment and combining with UPLC–QTOF–MS E on KC, rapid separation and analysis are achieved within 25 min with rapid identification of 41 main components. Therefore, in contrast to previous reports (Dan, Song, Wei, & Fan, ; Song et al, ), this study provides a rapid separation and high‐throughput analysis of the bioactive components of KC, to gain a more comprehensive understanding of them. It contributes to study of the pharmacodynamics material basis and control of drug quality and thus provides security for effective and safe drug use.…”

“…In the KC prescription described above, the complex bioactive components such as Herba Ephedrae and Pericarpium Papaveris are the principal medical materials, which are called the monarch drugs according to the Chinese medicine theory. Ephedra alkaloids such as ephedrine and pseudoephedrine are from the Herba Ephedrae (Haller, Iii, & Benowitz, ; Tang, Zheng, Chen, Chen, & Yu, ), which reduce bronchial asthma (Lee, ; Song et al, ) through acting on the central nervous system (CNS) (Berman, Setty, Steiner, Kaufman, & Skotzko, ; Lee, ; Wooltorton & Sibbald, ) and are associated with adrenergic receptors (Berman et al, ; Lee, ). Pericarpium Papaveris contains morphine, narcotine, papaverine, and so on (Lin et al, ), and relieves a cough and provides analgesia (Pichini, Altieri, Pellegrini, Zuccaro, & Pacifici, ; Liu & Tong, through acting on the CNS.…”

Validated LC–MS/MS method for quantitation of demethylbellidifolin in rat plasma and its application to pharmacokinetic and bioavailability studies

“…Unfortunately, the limit of quantification of 48 ng/mL is not sensitive enough for oral pharmacokinetic study. Liquid chromatography tandem with mass spectrometry (LC–MS/MS) has been widely accepted to be the predominant tool for quantitative analysis of herbal medicines including xanthone compounds in bioanalytical samples as it provides favorable specificity and sensitivity (Liu et al, ; Song et al, ). Recently, an LC–MS/MS method was reported for the determination of demethylbellidifolin in the presence of other xanthones in rats after consumption of G. acuta extract (Wang et al, ).…”