An accurate and precise spectrophotometric method is presented for the determination of zolmitriptan (ZMT) based on the formation of a red color product with vanillin in presence of concentrated H2SO4, with the chromogen being measured at 580？nm. The reaction proceeds quantitatively at room temperature in 10？min. The calibration curve is linear over the range 5.0–90.0？μg？mL？1 and described by the regression equation with a regression coefficient of 0.9994 . The calculated molar absorptivity and Sandell sensitivity values are 3.3 × 103 L？mol？1？cm？1 and 0.0872？μg？cm？2, respectively. The limits of detection (LOD) and quantification (LOQ) calculated as per ICH guidelines are 1.26 and 3.81？μg？mL？1, respectively. The within-day accuracy expressed as relative error was better than 1.78% with precision (RSD) ranging from 0.83 to 1.45%. The between-day accuracy ranged from 1.21 to 1.84% with a precision less than 1.66%. The method was successfully applied to the analysis of one brand of tablet containing zolmitriptan. The results obtained were in agreement with those obtained by published reference method. The accuracy was also checked by placebo blank and synthetic mixture analyses besides recovery study via standard addition procedure. 1. Introduction The antimigraine drug zolmitriptan (Figure 1) is a selective agonist of serotonin (5-hydroxytryptamine; 5-HT) type 1B and 1D receptors and chemically known as (4S)-4-[[3-[2-(dimethylamino) ethyl]-1H-indol-5-yl] methyl]-2-oxazolidinone. Zolmitriptan (ZMT) binds with high affinity to human 5-HT1B and 5-HT1D receptors leading to cranial blood vessel constriction. The therapeutic activity of ZMT for the treatment of migraine headache can most likely be attributed to the agonist effects at the 5HT1B/1D receptors on intracranial blood vessels (including the arteriovenous anastomoses) and sensory nerves of the trigeminal system, which result in cranial vessel constriction and inhibition of proinflammatory neuropeptide release [1]. Figure 1: Structure of ZMT. ZMT is not included in any pharmacopeia. Literature survey reveals that few analytical methods have been published for analysis of ZMT in human plasma and include high-performance liquid chromatography (HPLC) with coulometric [2], mass spectrometric detection [3–5], and liquid chromatography-mass spectrometry [1, 6, 7]. High-performance liquid chromatography (HPLC) with UV-detection has been widely used for the quantitative determination of ZMT in pharmaceuticals [8–15]. Ultraperformance liquid chromatography (UPLC) [16], liquid chromatography-mass spectrometry
References
[1]
B. Kilic, T. Ozden, S. Toptan, and S. Ozilhan, “Simultaneous LC-MS-MS determination of zolmitriptan and its active metabolite N-desmethylzolmitriptan in human plasma,” Chromatographia, vol. 66, pp. S129–S133, 2007.
[2]
E. M. Clement and M. Franklin, “Simultaneous measurement of zolmitriptan and its major metabolites N-desmethylzolmitriptan and zolmitriptan N-oxide in human plasma by high-performance liquid chromatography with coulometric detection,” Journal of Chromatography B, vol. 766, no. 2, pp. 339–343, 2002.
[3]
J. Yao, Y. Qu, X. Zhao et al., “Determination of zolmitriptan in human plasma by high performance liquid chromatography-electrospray mass spectrometry and study on its pharmacokinetics,” Journal of Chinese Pharmaceutical Sciences, vol. 14, no. 1, pp. 25–28, 2005.
[4]
Z. Zhang, F. Xu, Y. Tian, W. Li, and G. Mao, “Quantification of zolmitriptan in plasma by high-performance liquid chromatography-electrospray ionization mass spectrometry,” Journal of Chromatography B, vol. 813, no. 1-2, pp. 227–233, 2004.
[5]
D. Wang, D. S. Ouyang, Z. R. Tan et al., “HPLC-MS determination of zolmitriptan in human plasma and research of its bioequivalence,” Chinese Journal of Pharmaceutical Analysis, vol. 27, no. 2, pp. 171–173, 2007.
[6]
H. H. Zhou, X. J. Peng, Z. R. Tan, D. S. Ouyang, L. J. Liu, and L. L. Dai, “LC-MS/MS determination of zolmitriptan and its active metabolite N-desmethyl-zolmitriptan in human plasma,” Chinese Journal of Pharmaceutical Analysis, vol. 30, no. 8, pp. 1407–1411, 2010.
[7]
X. Chen, D. Liu, Y. Luan, F. Jin, and D. Zhong, “Determination of zolmitriptan in human plasma by liquid chromatography-tandem mass spectrometry method: application to a pharmacokinetic study,” Journal of Chromatography B, vol. 832, no. 1, pp. 30–35, 2006.
[8]
E. K. S. Vijayakumar, M. A. Samel, S. B. Bhalekar, and S. M. Pakhale, “A new stability indicating HPLC method for related substances in zolmitriptan,” Indian Journal of Pharmaceutical Sciences, vol. 72, no. 1, pp. 119–122, 2010.
[9]
M. M. Annapurna and B. Nanda, “Validated RP method for the determination of zolmitriptan—a serotonin 5-HT receptor agonist,” Journal of Pharmacy and Nutrition Sciences, vol. 1, no. 1, pp. 9–14, 2011.
[10]
D. G. Sankar, A. Nagesh Babu, A. Rajeshwari, and M. Vamsi Krishna, “Development and validation of RP-HPLC method for estimation of zolmitriptan in tablet dosage forms,” Asian Journal of Chemistry, vol. 21, no. 7, pp. 5019–5022, 2009.
[11]
M. K. Srinivasu, B. M. Rao, G. Sridhar, P. R. Kumar, K. B. Chandrasekhar, and A. Islam, “A validated chiral LC method for the determination of Zolmitriptan and its potential impurities,” Journal of Pharmaceutical and Biomedical Analysis, vol. 37, no. 3, pp. 453–460, 2005.
[12]
P. V. Sagar, D. Kumar, S. Dey, and H. B. Samal, “Simultaneous estimation of rizatriptan, sumatriptan and zolmitriptan by RP-HPLC method in bulk,” Journal of Pharmacy Research, vol. 3, no. 12, pp. 2930–2933, 2010.
[13]
M. Induri, R. M. Bhagavan, P. Y. Rajendra, R. K. Pavankumar, R. Boddu, and R. Sarva, “A validated RP-HPLC method for the quantification of zolmitriptan in tablet dosage form,” Der Pharma Chemica, vol. 2, no. 5, pp. 351–357, 2010.
[14]
D. Rambabu, B. Bhoomaiah, R. S. C. Phani, and K. B. Krishna, “Validated RP-HPLC method for the estimation of Zolmitriptan in formulation,” Pharmacophore, vol. 2, no. 2, pp. 150–155, 2011.
[15]
N. U. Rani, R. S. Rao, K. Saraswathi, and T. E. G. K. Murthy, “Development and validation of LC method for the estimation of Zolmitriptan in pharmaceutical dosage form,” Pharmacophore, vol. 2, no. 3, pp. 195–200, 2011.
[16]
Y. K. Reddy, G. V. S. Reddy, and K. N. Jayaveera, “A new stability indicating RP-UPLC method for related substances in zolmitriptan,” African Journal of Scientific Research, vol. 1, no. 1, pp. 50–62, 2011.
[17]
B. M. Rao, M. K. Srinivasu, G. Sridhar, P. R. Kumar, K. B. Chandrasekhar, and A. Islam, “A stability indicating LC method for zolmitriptan,” Journal of Pharmaceutical and Biomedical Analysis, vol. 39, no. 3-4, pp. 503–509, 2005.
[18]
B. Uslu and D. Canbaz, “Anodic voltammetry of zolmitriptan at boron-doped diamond electrode and its analytical applications,” Pharmazie, vol. 65, no. 4, pp. 245–250, 2010.
[19]
S. K. Acharjya, M. E. B. Rao, B. V. V. R. Kumar, and M. M. Annapurna, “UV-spectrophotometric methods for the determination of zolmitriptan in bulk and pharmaceutical dosage forms,” Journal of Advanced Scientific Research, vol. 2, no. 3, pp. 42–47, 2011.
[20]
T. E. G. K. Murthy and K. Veditha, “Spectrophotometric estimation of zolmitriptan,” Indian Pharmacist, vol. 9, no. 12, pp. 57–60, 2011.
[21]
D. G. Sankar, A. N. Babu, A. Rajeswari, M. V. Krishna, and K. V. Devi, “Spectrophotometric determination of zolmitriptan in pharmaceutical dosage forms,” Asian Journal of Chemistry, vol. 20, no. 6, pp. 4960–4962, 2008.
[22]
A. Raza, T. M. Ansari, and S. B. Niazi, “A novel spectrophotometric method for the determination of zolmitriptan in pharmaceutical formulations,” Journal of the Chinese Chemical Society, vol. 54, no. 6, pp. 1413–1417, 2007.
[23]
Z. Aydogmus and I. Inanli, “Extractive spectrophotometric methods for determination of zolmitriptan in tablets,” Journal of AOAC International, vol. 90, no. 5, pp. 1237–1241, 2007.
[24]
B. L. Joseph and R. B. Wallace, “Condensations of secondary amines with aldehydes and naphthols,” Journal of American Chemical Society, vol. 52, no. 4, pp. 1655–1659, 1930.
[25]
M. A. Youngman and S. L. Dax, “Solidphase Mannich condensation of amines, aldehydes, and alkynes: investigation of diverse aldehyde inputs,” Journal of Combinatorial Chemistry, vol. 3, no. 5, pp. 469–472, 2001.
[26]
O. Z. Devi, K. Basavaiah, K. B. Vinay, and H. D. Revanasiddappa, “Sensitive spectrophotometric determination of metoclopramide hydrochloride in dosage forms and spiked human urine using vanillin,” Arabian Journal of Chemistry, 2011.
[27]
“Validation of analytical procedures: text and methodology,” in Proceedings of the International Conference on Harmonization of Technical Requirements Registration of Pharmaceuticals for Human Use, ICH Harmonized Guideline, Q2 (R1), complementary guideline on methodology, London, UK, November 1996.
