Spectrophotometric determination of acidity constants of 4‐dedimethylamino sancycline (Col‐3), a new antitumor drug

Abstract

A spectrophotometric technique was used to determine the acidity constants of 4-dedimethylamino sancycline (Col-3), a new antitumor drug. The apparent pKa values of Col-3 in 0.5% methanol aqueous media at approximately 25 degrees C with a constant ionic strength of 0.2 were calculated manually and graphically to be 5.64 +/- 0.17 (pKa1) and 8.35 +/- 0.07 (pKa2). In addition, the computer program SQUAD was used to confirm Col-3 pKa values. The pKa values obtained by SQUAD were pKa1 5.63 +/- 0.14 and pKa2 8.39 +/- 0.04. These results are in agreement with the tetracycline-like structure of Col-3.

Factors Involved in the Pharmacokinetics of COL‐3, a Matrix Metalloproteinase Inhibitor, in Patients with Refractory Metastatic Cancer: Clinical and Experimental Studies

“…TLC plates were developed in a solvent solution containing n‐butanol/acetone/water (35:35:30 (v/v)) modified to determine quaternary ammonium‐linked glucuronides 21 . The modification was necessary to increase the stability of COL‐3 during chromatography because COL‐3 degrades in basic media to four separate products 22 . The TLC plates were dried and exposed to Biomax MR film (Eastman Kodak Co., Rochester, NY) for 7 days.…”

Reversed-phase liquid chromatography method to determine COL-3, a matrix metalloproteinase inhibitor, in biological samples

“…COL-3 possesses the first two of the acidic groupings of the tetracyclines, but due to the absence of the dimethyammonium functional group at C4, COL-3 not the third pK a . Using a spectrophotometric technique, the apparent pK a values of COL-3, determined in 0.5% methanol aqueous media at 25 • C with a constant ionic strength of 0.2, are 5.64 (pK a1 ) and 8.35 (pK a2 ) [13].…”

Structure and properties of the new complexes of platinum (II) with the chemically modified tetracycline CMT-3: A theoretical DFT study

“…The main form present in the medium was characterized experimentally using high-performance liquid chromatography (HPLC) over the pH range of 2-10 by Yalkowsky et al [36,45]. In addition they also reported the UV/Vis electronic spectra, obtained at the different pHs.…”

“…In addition they also reported the UV/Vis electronic spectra, obtained at the different pHs. According to the pKa values (5.6 and 8.35), the CMT-3 molecule exists mainly as the ionized species LH À (O3) in the biological medium (pH 7.4) [36,45].…”