Ayşegül DOĞAN, Merve Banu POLAT, Nursabah E. BAŞCI

Spectrophotometry, potentiometry and HPLC in determination of acidity constant for cabergoline and tadalafil

Acidic dissociation constant (pKa) is an important physicochemical parameter in absorption, dissociation and elimination mechanisms of drugs in body. Various analytical methods are utilized for the determination of pKa values of pharmaceutical active ingredients, and potentiometry, spectrophotometry and HPLC are the most commonmethods. Cabergoline is dopaminergic ergoline derivative having a powerful and long-term prolactin reducing effect, which is used for the treatment of Parkinson disease. Tadalafil leads an increasing cGMP level in Corpus cavernous, during secretion of nitric oxide in sexual arousal. In the presented study, detection of pKa values for Cabergoline and Tadalafil by using potentiometry, spectrophotometry and HPLC was investigated. The pKa value for Cabergoline wasrespectively found to be 6.42, 6.05 and 6.20 by spectrophotometry, potentiometry and HPLC. Spectrophotometric pKa value was significantly different (p>0.05) from others, and potentiometry and spectrophotometry were appropriate for pKa value determination of Cabergoline. The pKa values for Tadalafil by potentiometry and spectrophotometry were found to be 3.52 and 3.44, respectively. But, in HPLC, no differentiation was observed in retention times of Tadalafil by increasing pH value of mobile phase. Developed methods for determination of pKa values for Cabergoline and Tadalafildemonstrated high repeatability values (RSD

PDF

___

Skoog D, West D, Holler F, Crouch S, Fundamentals of Analytical Chemistry, eighth ed., Brooks/Cole, New York, USA 1992.
Kayaalp O, Tıbbi Farmakoloji, Hacettepe-Taş, Türkiye 1996.
Colao A, Lombardi G, Annunziato L. Cabergoline. Expert Opin Pharmacother. 2000; 1(3): 555-574. [CrossRef]
Curran MP, Perry CM. Cabergoline: a review of its use in the treatment of Parkinson's disease. Drugs. 2004;64(18):2125-2141. [CrossRef]
Forgue ST, Patterson BE, Bedding AW, Payne CD, Phillips DL, Wrishko RE, Mitchell MI. Tadalafil pharmacokinetics in healthy subjects. Br J Clin Pharmacol.2006;61(3):280-288. [CrossRef]
Pianezzola E, Bellotti V, La Croix R, Strolin Benedetti M. Determination of cabergoline in plasma and urine by highperformance liquid chromatography with electrochemical detection. J Chromatogr. 1992 ;574(1):170-174. [CrossRef]
Igarashi K, Hotta K, Kasuya F, Abe K, Sakoda S. Determination of cabergoline and L-dopa in human plasma using liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2003;792(1):55- 61. [CrossRef]
Kimball BA, DeLiberto TJ, Johnston JJ. Determination of cabergoline by electrospray ionization tandem mass spectrometry: picogram detection via column focusing sample introduction. Anal Chem. 2001;73(20):4972-4976. [CrossRef]
Allievi C, Dostert P. Quantitative determination of cabergoline in human plasma using liquid chromatography combined with tandem mass spectrometry. Rapid Commun Mass Spectrom. 1998;12(1):33-39. [CrossRef]
Paul G, Winnik W, Hughes N, Schweingruber H, Heller R, Schoen A. Accurate mass measurement at enhanced massresolution on a triple quadrupole mass-spectrometer for the identification of a reaction impurity and collisionallyinduced fragment ions of cabergoline. Rapid Commun Mass Spectrom. 2003;17(6):561-568. [CrossRef]
Piroozi F, Ghasemi E, Qomi M, Rezaee R, Hashemian F. Hollow fiber liquid phase microextraction combined with high performance liquid chromatography for preconcentration and determination of cabergoline ın biological samples. J Liq Chromatogr Relat Technol. 2014;37(5):760-771. [CrossRef]
Zang Q, Liu Y, He J, Yue X, Zhang R, Wang R, Abliz Z. A sensitive and rapid HPLC-MS/MS method for the quantitative determination of trace amount of bromocriptine in small clinical prolactinoma tissue. J Chromatogr B Analyt Technol Biomed Life Sci. 2015;989:91-97. [CrossRef]
Onal A, Sagirli O, Şensoy D. Selective LC determination of cabergoline in the bulk drug and in tablets: in vitro dissolution studies. Chromatographia. 2007; 65(9-10): 561-567. [CrossRef]
Onal A, Caglar S. Spectrophotometric determination of dopaminergic drugs used for parkinson’s disease, cabergoline and ropinirole in pharmaceutical preparations. Chem Pharm Bull. 2007; 55(4) 629-631. [CrossRef]
Salman D, Dogan A, Basci NE. Spectrophotometric analysis of cabergoline in pharmaceutical preparations. Lat Am J Pharm. 2011; 30 (2): 304-310.
Jain R, Sinha A. A graphene based sensor for sensitive voltammetric quantification of cabergoline. J Electrochem Soc. 2014; 161(5): H314-H320. [CrossRef]
Al KA, Gouda AA. Spectrophotometric determination of tadalafil in pure and dosage forms. Chem Ind Chem Eng Q. 2011; 17 (2): 125-132. [CrossRef]
Anandakumar K, Varadharajan K, Subathrai R, Jothieswari D,Seyal GS. Estimation of tadalafil in bulk and in formulation by uv-visible spectrophotometry. Asian J Res Chem. 2010; 3(1): 54-57. [CrossRef]
Fraihat S. Spectrophotometric methods for the determination of tadalafil in pharmaceutical forms. Int J Pharm Sci. 2014; 6 (7): 443-445.
Jain VM, Anuj J, Anurekha S, Alankar T, Umesh V, Jain SK. A validated uv spectrophotometric method for determination of tadalafil in bulk and solid dosage form. J Adv Drug Res. 2012; 2(1): 13-18.
Rajeswari KR, Rao AL, Rao NS. Spectrophotometric method for the determination of tadalafil in pure and tablet dosage form. Int J Chem Sci. 2006; 4 (3): 735-737.
Nesalin J, Babu C, Kumar GV, Mani TT. Validated extractive spectrophotometric estimation of tadalafil in tablet dosage form. E-J Chem. 2009; 6(3): 611-614. [CrossRef]
Pani Kumar DA, Vijaya Durga D, Hima Bindu S, Sunitha G, Ramakrishna K. Spectrophotometric quantification of tadalafil by oxidative coupling reaction with mbth reagent. Anal Chem: Indian J. 2013; 13(9): 361-364.
Yunoos M, Sankar DG, Kumar BP, Hameed S. UV spectrophotometric method for the estimation of tadalafil in bulk and tablet dosage form. E-J Chem. 2010; 7(3): 833-836. [CrossRef]
Amin G, Chapla B, Pandya A, Kakadiya J, Baria D. Development and validation of dual wavelength u spectrophotometric method for simultaneous estimation of tadalafil and dapoxetine hydrochloride in their combined tablet dosage form. Int J Pharm Res Bio-Sci. 2012; 1 (2): 247-255.
Lakshmi VN, Kumar DR, Vardhan S, Rambabu C. Validated spectrophotometric methods for the determination of tadalafil in pharmaceutical formulations. Orient J Chem. 2009; 25(3): 791-794.
Khan ZG, Patil AS,Shirkhedkar AA. Estimation of tadalafil using derivative spectrophotometry in bulk material and in pharmaceutical formulation. Int J Spectrosc. 2014; Article ID 392421. [CrossRef]
Yehia MA, Rezk MR, El-Sayed MA, Kawy MA. Stability-indicating methods for determination of tadalafil in presence of its degradation product. Anal Chem: Indian J. 2014; 14 (9): 351-368.
Fejős I, Neumajer G, Béni S, Jankovics P. Qualitative and quantitative analysis of PDE-5 inhibitors in counterfeit medicines and dietary supplements by HPLC-UV using sildenafil as a sole reference. J Pharm Biomed Anal. 2014;98:327-333. [CrossRef]
Gratz SR, Flurer CL, Wolnik KA. Analysis of undeclared synthetic phosphodiesterase-5 inhibitors in dietary supplements and herbal matrices by LC-ESI-MS and LC-UV. J Pharm Biomed Anal. 2004;36(3):525-533. [CrossRef]
Luo Z, Lei Y, Yang D, Li Y. High performance liquid chromatography method for simultaneously detecting phosphodiesterase type-5 (pde5) inhibitors illegally added in chinese medicine, health food and food with kidney invigorating and yang strengthening effects. CN101587102A. 2009
Park M, Ahn S. Quantitative analysis of sildenafil and tadalafil in various fake drugs recently distributed in Korea. J Forensic Sci. 2012;57(6):1637-1640. [CrossRef]
Zhiwu S, Hong.-bing T, Qun L, Jinren Duan. HPLC determination of 3 contraband drugs (tadalafil, sildenafil and vardenafil) in health-care foodstuffs. Lihua Jianyan, Huaxue Fence 2008; 44(6): 540-542.
Wang Z, Zhao H, Jiang X, Shi J. Content analysis of sildenafil and tadalafi in 15 aphrodisiac health products. Zhongguo Yaoshi (Wuhan, China). 2012; 15 (6): 895-896.
Rabbaa-Khabbaz L, Daoud RA. A sensitive and simple high performance liquid chromatographic method for quantification of tadalafil in human serum. J Appl Res. 2006; 6(1): 170-175.
Shakya AK, Abu-awwad AN, Arafat TA, Melhim M. Validated liquid chromatographic-ultraviolet method for the quantitation of tadalafil in human plasma using liquid-liquid extraction. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;852(1-2):403-408. [CrossRef]
Barot TG, Patel PK. Determination of tadalafil in pure powder and tablet dosage form by high-performance liquid chromatography. J AOAC Int. 2010;93(2):516-522.
Bojanapu A, Subramaniam AT, Munusamy J, Dhanapal K, Chennakesavalu J, Sellappan M, Jayaprakash V. Validation and method development of tadalafil in bulk and tablet dosage form by RP-HPLC. Drug Res (Stuttg). 2015;65(2):82-85. [CrossRef]
Chandran M, Kannan K. A validated RP-HPLC method for simultaneous estimation of tadalafil and dapoxetine in tablet dosage form. J Sci Res Pharm. 2012; 1(2): 36-39.
De Orsi D, Pellegrini M, Marchei E, Nebuloni P, Gallinella B, Scaravelli G, Martufi A, Gagliardi L, Pichini S. High performance liquid chromatography-diode array and electrospray-mass spectrometry analysis of vardenafil, sildenafil, tadalafil, testosterone and local anesthetics in cosmetic creams sold on the Internet web sites. J Pharm Biomed Anal. 2009;50(3):362-369. [CrossRef]
Hashem H, Ibrahim AE, Elhenawee M. Chromatographic Analysis of some drugs employed in erectile dysfunction therapy: Qualitative and quantitative studies using calixarene stationary phase. J Sep Sci. 2014; 37 (20): 2814-2824. [CrossRef]
Kannappan N, Yada D, Shashikanth MR. Method development and validation of stability indicating methods for assay of tadalafil and sildenafil citrate by HPLC. Int J Chem Tech Res. 2010; 2 (1): 329-333.
Patel JK, Patel NK. Stability-indicating RP-HPLC method for the determination of ambrisentan and tadalafil in pharmaceutical dosage form. Sci Pharm. 2014;82(4):749-763. [CrossRef]
Rajeshwari M, Chenthilnathan A, Rama K. Validated RP-HPLC method for simultaneous estimation of tadalafil and dapoxetine hydrochloride in combined pharmaceutical dosage forms. Int J Pharm Biol Sci. 2014; 4 (2): 72-82.
Yang YJ, Song DM, Jiang WM, Xiang BR. Rapid resolution RP-HPLC-dad method for simultaneous determination of sildenafil, vardenafil, and tadalafil in pharmaceutical preparations and counterfeit drugs. Anal Lett. 2010; 43(3): 373- 380. [CrossRef]
Yehia MA, Rezk MR, El-Sayed MA, Abdel Kawy M. Stability-indicating methods for determination of tadalafil in presence of its degradation product. Anal Chem: Indian J. 2014; 14(9): 351-362.
Lee JH, Kim HJ, Noh E, Kim JY, Cho SH, Do JA, Yoon CY, Cho S, Kim WS. Identification and screening of a tadalafil analogue found in adulterated herbal products. J Pharm Biomed Anal. 2015;103:80-84. [CrossRef]
Luo Z, Deng K, Le Y. System methods for determination of adulteration in anti-fatigue health food. Yaowu Fenxi Zazhi. 2011; 31(11): 2091-2094.
Savaliya AA, Shah RP, Prasad B, Singh S. Screening of Indian aphrodisiac ayurvedic/herbal healthcare products for adulteration with sildenafil, tadalafil and/or vardenafil using LC/PDA and extracted ion LC-MS/TOF. J Pharm Biomed Anal. 2010;52(3):406-409. [CrossRef]
Sheng Z-W, Wang P,Tang H.-B. Determination of tadalafil in health food with RP HPLC. Zhongguo Weisheng Jianyan Zazhi. 2007; 17 (1): 92-93.
Xia C, Wang D, Liu X. Method for simultaneous determination of sildenafil citrate and tadalafil added illegally in traditional chinese medicine preparation. Yaowu Fenxi Zazhi. 2008; 28(11): 1909-1911.
Xing J-B, Cao H, Zhang J, Shan T-T, Shui C-H., Chen Y-M. Simutaneous determination of 7 illegal components illegally added in traditional chinese medicine and health food by HPLC. Shizhen Guoyi Guoyao. 2014; 25(2): 451- 453.
Ulloa J, Sambrotta L, Redko F, Mazza ON, Garrido G, Becher EF, Muschietti L. Detection of a tadalafil analogue as an adulterant in a dietary supplement for erectile dysfunction. J Sex Med. 2015;12(1):152-157. [CrossRef]
Babic S, Horvat AJM, Pavlovic DM. Determination of pKa values of active pharmaceutical ingredients. Trends Anal Chem. 2007; 26 (11): 1043-1061. [CrossRef]
Albert A, Serjeant E, The Determination of Ionization Constants, third ed., Chapman and Hall, New York, USA 1984.
Gran G. Determination of the equvalence points in potentiometric titrations: Part II. Analyst 1952; 77: 661-671.