Enantiomeric separation of tramadol and its active metabolite in human plasma by chiral high-performance liquid chromatography: Application to pharmacokinetic studies

Campanero, Miguel Ángel; Calahorra, B.; Valle, Marta; Trocóniz, Iñaki F.; Honorato, J.

doi:10.1002/(sici)1520-636x(1999)11:4<272::aid-chir3>3.0.co;2-i

Cited by 47 publications

(28 citation statements)

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“…A number of high-performance liquid chromatographic (HPLC) methods with ultraviolet [6,8,9], fluorescence [10,11], electrochemical [12] and MS detection [13] described. Achiral HPLC analytical methods [6,8,9,[14][15][16][17][18][19][20] are routinely used in pharmacokinetic and bioequivalence studies, while chiral HPLC methods [10][11][12][13] are very important for the determination of the enantiomeric ratios of tramadol and its metabolites.…”

Section: Introductionmentioning

confidence: 99%

“…Achiral HPLC analytical methods [6,8,9,[14][15][16][17][18][19][20] are routinely used in pharmacokinetic and bioequivalence studies, while chiral HPLC methods [10][11][12][13] are very important for the determination of the enantiomeric ratios of tramadol and its metabolites. Although the tramadol molecule contains a benzene ring, UV detection is unsuitable for its analysis in plasma due to lack of sensitivity [14,9].…”

Section: Introductionmentioning

confidence: 99%

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Development and validation of a rapid HPLC method for simultaneous determination of tramadol, and its two main metabolites in human plasma

Rouini

Ardakani

Soltani

et al. 2006

Journal of Chromatography B

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development and validation of a rapid HPLC method for simultaneous determination of tramadol, and its two main metabolites in human plasma

Rouini

Ardakani

Soltani

et al. 2006

Journal of Chromatography B

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“…Plasma concentrations of (ϩ)-T and (ϩ)-M1 were determined by a sensitive and stereoselective HPLC assay (Campanero et al, 1999). Plasma samples (50 l) were transferred into glass tubes mixed with 50 l of internal standard (ketamine HCl), 1 ml of Tris buffer (pH 9.5, 0.05 M), and 6 ml of tert-butyl methylether.…”

Section: Drug Assaysmentioning

confidence: 99%

Pharmacokinetic/Pharmacodynamic Modeling of the Antinociceptive Effects of (+)-Tramadol in the Rat: Role of Cytochrome P450 2D Activity

Garrido

Sayar²,

Segura³

et al. 2003

J Pharmacol Exp Ther

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In this study the role of cytochrome P450 2D (CYP2D) in the pharmacokinetic/pharmacodynamic relationship of (ϩ)-tramadol [(ϩ)-T] has been explored in rats. Male Wistar rats were infused with (ϩ)-T in the absence of and during pretreatment with a reversible CYP2D inhibitor quinine (Q), determining plasma concentrations of Q, (ϩ)-T, and (ϩ)-O-demethyltramadol [(ϩ)-M1], and measuring antinociception. Pharmacokinetics of (ϩ)-M1, but not (ϩ)-T, was affected by Q pretreatment: early after the start of (ϩ)-T infusion, levels of (ϩ)-M1 were significantly lower (P Ͻ 0.05). However, at later times during Q infusion those levels increased continuously, exceeding the values found in animals that did not receive the inhibitor. These results suggest that CYP2D is involved in the formation and elimination of (ϩ)-M1. In fact, results from another experiment where (ϩ)-M1 was given in the presence and in absence of Q showed that (ϩ)-M1 elimination clearance (CL ME0 ) was significantly lower (P Ͻ 0.05) in animals receiving Q. Inhibition of both (ϩ)-M1 formation clearance (CL M10 ) and CL ME0 were modeled by an inhibitory E MAX model, and the estimates (relative standard error) of the maximum degree of inhibition (E MAX ) and IC 50 , plasma concentration of Q eliciting half of E MAX for CL M10 and CL ME0 , were 0.94 (0.04), 97 (0.51) ng/ml, and 48 (0.42) ng/ml, respectively. The modeling of the time course of antinociception showed that the contribution of (ϩ)-T was negligible and (ϩ)-M1 was responsible for the observed effects, which depend linearly on (ϩ)-M1 effect site concentrations. Therefore, the CYP2D activity is a major determinant of the antinociception elicited after (ϩ)-T administration.Tramadol (T) is a safe and effective analgesic used during the last two decades in the treatment of several types of pain (Rhoda et al., 1993;Raffa et al., 1995). Despite its long-term use, the understanding and prediction of the time course of its pharmacological effects are still hampered by the presence of active metabolites and the coexistence of opioid and nonopioid mechanisms. In fact, T is administered as a racemic mixture of two enantiomers, (ϩ)-T and (Ϫ)-T, which are metabolized in the liver forming, among others, the two main, respectively. Data from literature suggest that (ϩ)-enantiomers show opioid properties, while (Ϫ)-enantiomers are able to inhibit the uptake of norepinephrine. This duality of action makes T an atypical opioid (Raffa et al., 1992;Raffa and Friderichs, 1996).Recently the antinociceptive properties of the two active metabolites of T, (ϩ)-M1 and (Ϫ)-M1, have been evaluated in the pharmacokinetic/pharmacodynamic (pk/pd) perspective in the rat. The results showed that (ϩ)-M1, in accord with its -opioid receptor agonist properties (Lai et al., 1996), was able to produce maximum antinociception in the tail-flick test; however, when (Ϫ)-M1, a monoamine re-uptake inhibitor (Frink et al., 1996), was given alone, no significant effects were found . However, Garrido et al., 2000 showed that in the presence of ...

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“…5 Chromatographic techniques, especially by HPLC have been given priority for the separation of enantiomers during the past several decades. [6][7][8][9] Numerous book chapters and review articles have dealt with the separation of chiral drugs by HPLC methods. [10][11][12][13][14] Chiral HPLC provides fast and accurate methods for chiral separation, and allows on-line detection and quantitation of both mass and optical rotation of enantiomers if appropriate detection devices are used.…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of a Chiral HPLC Method for Quantitative Analysis of Enantiomeric Escitalopram

Rahman

Haque

Rahman

et al. 2018

Dhaka Univ. J. Pharm. Sci

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ABSTRACT:In the present study a rapid, accurate and precise chiral HPLC method was developed and validated for enantiomeric separation of racemate citalopram and escitalopram according to the guidelines of United States of Pharmacopeia (USP) and International Conference on Harmonization (ICH). The chiral chromatographic separation was achieved with ammonium acetate/ ethanol/ 2-propanol/ methylene dichloride (100 : 150 : 70 : 30, v/v) at a flow rate of 0.5 ml/min using a chiral CD-PH column. The HPLC analyses were monitored at 254 nm. The method showed a good linearity with regression coefficient (r 2 ) of 0.998 in the range of 20.0-70.0 µg/ml for escitalopram. The detection limit (LOD), quantitation limit (LOQ) and average percentage of recovery for escitalopram were found to be 2.54, 7.68 µg/ml and 100.28% to 102.86%, respectively. The percentage of relative standard deviation (%RSD) for intra-and inter-day precision were found as 0.16% and 0.09%, respectively. The established method proved as reproducible with a %RSD value of less than 2 and having the robustness within specified limit. The present study also showed the enantiomeric purity or excess (%ee) of seven pharmaceutical preparations of escitalopram. Thus the proposed chiral method can be applied for the enantiomeric purity determination of escitalopram formulations.

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Enantiomeric separation of tramadol and its active metabolite in human plasma by chiral high-performance liquid chromatography: Application to pharmacokinetic studies

Cited by 47 publications

References 11 publications

Development and validation of a rapid HPLC method for simultaneous determination of tramadol, and its two main metabolites in human plasma

Development and validation of a rapid HPLC method for simultaneous determination of tramadol, and its two main metabolites in human plasma

Pharmacokinetic/Pharmacodynamic Modeling of the Antinociceptive Effects of (+)-Tramadol in the Rat: Role of Cytochrome P450 2D Activity

Development and Validation of a Chiral HPLC Method for Quantitative Analysis of Enantiomeric Escitalopram

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