Mirza T, Lunn M J, Keeley F J, George R C, Bodenmiller J R
United States Pharmacopeial Convention, Rockville, MD 20852, USA.
J Pharm Biomed Anal. 1999 Apr;19(5):747-56. doi: 10.1016/s0731-7085(98)00299-4.
A method using pharmacologically based and visual limit of detection criteria to determine the acceptable residue level for Meclizine Hydrochloride (MH) on pharmaceutical manufacturing equipment surfaces after cleaning is described. A formula was used in order to determine the pharmacologically safe cleaning level for MH. This level was termed as specific residual cleaning Level (SRCL) and calculated to be 50 microg 100 cm(-2). The visual limit of detection (VLOD) was determined by spiking different levels of MH on stainless steel plates and having the plates examined by a group of observers. The lowest level that could be visually detected by the majority of the observers, 62.5 microg 100 cm(-2), was considered as the VLOD for MH. The lower of the SRCL and VLOD values, i.e. 50 microg 100 cm(-2), was therefore chosen as the cleaning acceptance criterion. A sensitive reversed-phase HPLC method was developed and validated for the assay of MH in swabs used to test equipment surfaces. Using this method, the mean recoveries of MH from spiked swabs and '180-Grit' stainless steel plates were 87.0 and 89.5% with relative standard deviations (RSD) of +/- 3.3 and +/- 2.4%, respectively. The method was successfully applied to the assay of actual swab samples collected from the equipment surfaces. The stability of MH on stainless steel plates, on cleaning swabs and in the extraction solution was investigated.
描述了一种使用基于药理学和视觉检测限标准来确定制药生产设备表面清洗后盐酸美克洛嗪(MH)可接受残留水平的方法。使用一个公式来确定MH的药理学安全清洗水平。该水平被称为特定残留清洗水平(SRCL),经计算为50微克/100平方厘米。通过在不锈钢板上添加不同水平的MH并让一组观察者检查这些板来确定视觉检测限(VLOD)。大多数观察者能够视觉检测到的最低水平,即62.5微克/100平方厘米,被视为MH的VLOD。因此,选择SRCL和VLOD值中较低的那个,即50微克/100平方厘米,作为清洗验收标准。开发并验证了一种灵敏的反相高效液相色谱法,用于检测用于测试设备表面的拭子中的MH。使用该方法,加标拭子和“180目”不锈钢板中MH的平均回收率分别为87.0%和89.5%,相对标准偏差(RSD)分别为±3.3%和±2.4%。该方法成功应用于从设备表面采集的实际拭子样品的检测。研究了MH在不锈钢板、清洗拭子和提取溶液中的稳定性。