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Voltammetric analysis of dantrolene and its active metabolite with indomethacin in rat plasma

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One of the most common issues introduced to primary care clinics is low back pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) and muscle relaxants medications are commonly prescribed, usually as combined therapy, in such conditions. When the muscle relaxants are concurrently prescribed with NSAIDs, their effect is reported to be additive and greater pain relief is achieved [1–3].

Indomethacin (IND) is chemically 1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-acetic acid (Figure 1) [4]. It is a NSAID showing anti-inflammatory, analgesic and antipyretic activities [5].

Structures of indomethacin and dantrolene.

IND is efficiently absorbed following oral administration, with plasma concentration, peaking after 1–4 h, it is extensively bound to plasma proteins (90%) and has wide intersubject variability in its elimination half-life [5]. It is metabolized in vivo.

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References

1 Kuritzky L, Samraj GP. Nonsteroidal anti-inflammatory drugs in the treatment of low back pain. J. Pain Res. 5, 579–590 (2012).

2 Luo X, Pietrobon R, Curtis LH, Hey LA. Prescription of nonsteroidal anti-inflammatory drugs and muscle relaxants for back pain in the United States. Spine 29(23), E531–E537 (2004).

3 Carlson JD, Peloquin J, Falowski S. Medications used for the treatment of back pain. In: Integrating Pain Treatment into Your Spine Practice. Falowski S, Pope J (Eds). Springer Library of Congress, Springer International Publishing, Basel, Switzerland, 99–108 (2016).

4 The United States Pharmacopoeia, The National Formulary, 33 Edition. United States Pharmacopoeial Convention, Inc., Washington, DC, USA, 2997–3001, 3860–3868 (2015).

5 Helleberg L. Clinical pharmacokinetics of indomethacin. Clin. Pharmacokinet. 6(4), 245–258 (1981).

6 Radi A-E. Preconcentration and voltammetric determination of indomethacin at carbon paste electrodes. Electroanalanysis 10(2), 103–106 (1998).

7 Vree TB, Van Den Biggelaar-Martea M, Verwey-Van Wissen CP. Determination of indomethacin, its metabolites and their glucuronides in human plasma and urine by means of direct gradient high-performance liquid chromatographic analysis. Preliminary pharmacokinetics and effect of probenecid. J. Chromatogr. 616(2), 271–282 (1993).

8 Liu S, Kamijo M, Takayasu T, Takayama S. Direct analysis of indomethacin in rat plasma using a column-switching high-performance liquid chromatographic system. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 767(1), 53–60 (2002). • This reference indicates metabolite of indomethacin is not found in plasma, so the parent drug is only quantified.

9 Singh AK, Jang Y, Mishra U, Granley K. Simultaneous analysis of flunixin, naproxen, ethacrynic acid, indomethacin, phenylbutazone, mefenamic acid and thiosalicycic acid in plasma and urine by high-performance liquid chromatography and gas chromatography–mass spectrometry. J. Chromatogr. B Biomed. Sci. Appl. 568(2), 351–361 (1991).

10 Ali AM. Cathodic adsorptive stripping voltammetric determination of the anti-inflammatory drug indomethacin. J. Pharm. Biomed. Anal. 18(6), 1005–1012 (1999). • This reference explains the mechanism of carbonyl group reduction.

11 El-Hefnawy GB, El-Hallag IS, Ghoneim EM, Ghoneim MM. Square-wave adsorptive cathodic stripping voltammetric determination of anti-inflammatory indomethacin drug in tablets and human serum at a mercury electrode. Anal. Bioanal. Chem. 376(2), 220–225 (2003). • This reference explains the mechanism of carbonyl group reduction.

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