Development and validation of a sensitive liquid chromatographic-tandem mass spectrometric method for the...

Cromolyn sodium is a safe compound with potent anti-allergic properties when used locally or topically. Clinical data from systemic exposure is not available because of the poor GI absorption when given orally. In order to evaluate a new approach to enhance the absorption and bioavailability of cromolyn sodium, a sensitive assay was needed to support an oral-dose study in humans. This paper describes a liquid chromatographic-tandem mass spectrometric (LC-MS-MS) method for the analysis of cromolyn sodium in human plasma. The method consists of a two-step extraction with subsequent analysis using a high-performance liquid chromatography electrospray tandem mass spectrometer system. The compounds were eluted isocratically on a C(18) column followed by a backflush. The total run time is 6 min. The standard curve of cromolyn sodium was over the range of 0.313 to 750 ng/mL with a lower limit of quantitation (LLOQ) of 0.313 ng/mL when 0.5 mL of plasma was used for analysis. The percent coefficient of variation (C.V.) for accuracy and precision (inter-assay and intra-assay) was less than 15% over the validated concentration range and the coefficients of determination, r(2), were >0.991577. The method is simple, sensitive, and selective, and has been successfully utilized for oral cromolyn sodium clinical studies.