Rinse-sampling was performed with extraction solvent. The volume of the rinsing liquid for the sampling point was 10 mL for 625 cm2 surface. RESULTS AND DISCUSSION antiangiogenic Establishing cleaning limits The acceptable limit for the drug residue must ensure the absence of cross contamination for subsequent batches manufactured in the affected equipment.[17] FDA’s guidance for determining residue limits requires a logical, practical, achievable and verifiable determination practice.[2] The basic principle of cleaning verification/validation is that the patient should not take more than 0.1% of the standard therapeutic dose (effective dose). The calculation formula is based on the dosage criteria.

[3,4] MAC is the maximum allowable carryover, STD is the minimal daily dose (active weight) of previous product, SF is a safety factor (1000), SBS is the smallest batch size of the subsequent product, and LWDS is the maximum daily dose (product weight) of the following product. An additional criterion is the 10 ppm (part per million) limit.[5] According to this criterion, not more than 10 ppm of the previously manufactured product is allowed to appear in the subsequent product. If the value, which is obtained from the calculation based on the dosage criterion, is greater than 10 ppm, then the 10 ppm criterion is applicable. The acceptable limit for residues (LA) is expressed in ��g/dm2. LA is the acceptance limit, A is the sampling area, R is the recovery of the sampling method, and TA is the total production line area.

Method development and optimization The main objective in this study has been to develop an UPLC method using isocratic conditions for the analysis of low quantities of duloxetine, trying to get a high peak in a short time. We selected 230 nm for the analysis because the drug has sufficient absorption and low quantities of duloxetine may be detected correctly. Furthermore, the calibration curves obtained at 230 nm show good linearity. The mobile phase very often used is the mixture of phosphate buffer and acetonitrile in different proportions. The run time was too long with the higher pH (above pH 4.0) and higher proportion of the buffer in the mobile phase. To solve this problem, several mobile phases were tested, varying their composition and pH, to obtain the chromatographic separation. The proposed mobile phase composed by 0.

01 M potassium dihydrogen ortho-phosphate, Batimastat pH adjusted to 3.0 with ortho-phosphoric acid and acetonitrile (60:40 v/v) gave best resolution and sensitivity with a very shorter run time. An Acquity UPLC? HSS T3 (100 �� 2.1 mm2) 1.8 ��m column was selected over an Acquity UPLC? BEH C18 (100 �� 2.1 mm2) 1.7 ��m column, to achieve good peak shape and symmetry. The injection volume was varied between 2 and 10 ��L, finally 5 ��L was chosen, because bigger volumes imply wider peaks without much enhancement of the signal-to-noise ratio. The flow rate of the mobile phase was kept 0.