Assessment of pharmacokinetic interaction between piracetam and l‐carnitine in healthy subjects

Abstract

A rapid, sensitive and specific method for quantifying piracetam in human plasma using Piracetam d-8 as the internal standard (IS) is described. The analyte and the IS were extracted from plasma by one-step precipitation of protein using an acetonitrile (100%). The extracts were analyzed by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC-MS/MS). The method had a chromatographic run time of 3.8 min and a linear calibration curve over the range 0.5-50 µg/mL (r > 0.99). This LC-MS-MS procedure was used to assess the bioavailability of two piracetam formulations: piracetam + l-carnitine (Piracar®; 270/330 mg tablet) and piracetam (Nootropil®; 800 mg tablet) in healthy volunteers of both sexes. The geometric means with corresponding 90% confidence interval (CI) for test/reference percentage ratios were 88.49% (90% CI = 81.19 - 96.46) for peak concentration/dose and 102.55% (90% CI = 100.62 - 104.51) for AUCinf /dose. The limit of quantitation of 0.5 µg/mL is well suited for pharmacokinetic studies in healthy volunteers. It was concluded that piracetam (Piracar®; 270/330 mg tablet) has a bioavailability equivalent to the piracetam (Nootropil®; 800 mg tablet) formulation with regard to both the rate and the extent of absorption.

Identification of l‐carnitine and its impurities in food supplement formulations by online column‐switching liquid chromatography coupled with linear ion trap mass spectrometry

“…Another impurity CTTA was not quantified because the standard is unavailable. Numerous reports on analytical methods for determination of l‐ carnitine in biological samples (plasma, serum, and urine), food supplements and pharmaceutical formulations have been published , but there are few reports on determining the impurities in l‐ carnitine. CTEA (crotonoylbetaine) was detected in pharmaceutical formulations of l‐ carnitine by ion pairs HPLC–UV, with the content at < 1% .…”

“…Other columns, such as HILIC columns, have also been used to determine carnitine and acylcarnitines in milk, human urine, serum, and plasma . A CN analytical column was used for analysis of piracetam and l‐ carnitine in human plasma .…”

L-carnitine+piracetam for fatigue and muscular strength of patients with post-poliomyelitis

“…However, the studies have shown the drugs have good bioavailability in conjunction and act in concentrations below the needed ones to act individually. 10,18 Costa RAP et al 10 further found that the drugs act on mitochondrial metabolism, preventing and/or improving mitochondrial dysfunction.…”

New Methods Used in Pharmacokinetics and Therapeutic Monitoring of the First and Newer Generations of Antiepileptic Drugs (AEDs)

“…They are focused on the assessment of pharmacokinetic interaction between PIR and l-carnitine in human plasma using piracetam d-8 as the internal standard and one-step precipitation of protein using acetonitrile. The extracts were analyzed by HPLC-MS/MS [94]. The HPLC methods describe using a mixture of an aqueous solution of perchloric acid, methanol or acetonitrile with protein precipitation and LLE with chloroform, 2-propanol, toluene or hexane mixture as a form of simple extraction [95,96].…”