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.[1] Reaction to m-cresol in commercial preparations of insulin to humans was reported by Dennis et al[2]. 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[6] secreted from parathyroid gland, is the principle homeostatic regulator of the level of blood calcium through its actions on kidney and bone.[7] 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.