All isomers are mainly eliminated by renal excretion in the form of above-mentioned conjugates. The oral LD50 of undiluted m-cresol in rats was 242 mg/kg bw. Clinical sign includes hypoactivity, selleck catalog salivation, tremors, and convulsions. Neither mortality nor clinical signs of toxicity were seen following exposure to saturated vapor concentration of either m-cresol or p-cresol. Inhalation of aerosols may, however, cause death, and mean lethal concentrations in rats were reported to be 29 mg/m3 for p-cresol and 58 mg/m3 for m-cresol. Reaction to m-cresol in commercial preparations of insulin to humans was reported by Dennis et al. The analysis of cresol-like chemicals in use for a long period of time has evolved from a number of nonspecific colorimetric methods to more selective separation techniques using gas chromatography (GC) or high performance liquid chromatography (HPLC).
[3�C5] The objective of our work was hence to develop a rapid and simple RP-HPLC method with UV detection, useful for routine quality control of m-cresol in PTH formulations. Human PTH, a peptide of 84 amino acid residues secreted from parathyroid gland, is the principle homeostatic regulator of the level of blood calcium through its actions on kidney and bone. Teriparatide (recombinant DNA origin) injection [recombinant human PTH (1�C34)] is a bone-forming agent used for the treatment of osteoporosis. The structure of Meta-cresol and PTH are given in Figure 1 (a) and (b), respectively. Figure 1 Structure of m��cresol The method developed was validated for parameters such as linearity, accuracy, and precision.
So far, to the best of our knowledge, no RP-HPLC method has been reported for determination of m-cresol in PTH formulations. MATERIALS AND METHODS Material, reagent, and chemicals HPLC-grade acetonitrile and methanol were purchased from Merck; tri-fluoro-acetic acid was purchased from Sigma Aldrich. Ultra pure water was obtained using Milli-Q? UF-Plus (Millipore) system; m-cresol was obtained from J.T. Baxter/Hedinger and was used for preparation of different dilutions; PTH API (Active Pharmaceutical Ingredient) having concentration of 400 ��g/mL was used for different dilutions of a PTH working standard. PTH formulation containing 250 ��g/mL PTH as active pharmaceutical ingredient was used as a test sample. All chemicals, i.e.
mannitol, sodium acetate, and glacial acetic, were of the highest purity available. Preparation of standard, mobile phase, and dilution buffer Formulation buffer Buffer containing 3 mg/mL m��cresol, 45.4 mg/mL mannitol, 0.1 mg/mL sodium acetate and 0.41 mg/mL glacial acetic acid in Milli Q water was prepared. It is similar as excipients used for PTH formulation. PTH working standard PTH (400 ��g/mL) was used for preparation of different diluted samples. m-cresol Anacetrapib standard An aliquot of 3 mg/mL was used for preparation of different dilutions. Mobile phase consisted of 0.