Development and Validation of a Liquid Chromatography-Mass Spectrometry Assay for Determination of Cromolyn Sodium in Skin Permeation Studies

Table 3

Comparison of previously established methods for CS detection and quantitation.

Method	LOD (μg/mL)	LOQ (μg/mL)	Application	Shortcomings	References
Spectrophotometry	0.22	0.67	Drug mixtures, epicrom eye drops	Does not investigate selectivity regarding endogenous skin components, and LOQ is not ideal for lower limits of drug detection in permeation studies	El-Zahar et al. (2020) [26]
HPLC-UV	0.563	1.719	Nasal formulations and combined drug nasal preparations	Sensitivity and selectivity are not tested for drug detection in cutaneous permeation studies	Fathy et al. (2017) [1]
AUC and FDSFS methods	0.21 and 0.02	0.63 and 0.07	Aqueous solutions prepared with water, nazocrom nasal spray	FDSFS has sufficient LOD and LOQ, however does not investigate potential skin component interference	Abdel-Aziz et al. (2014) [31]
HPLC-UV	0.707	2.143	Aqueous solutions prepared from stock, fluca eye drops	Lacks sensitivity and does not evaluate potential skin interference	El-Bagary et al. (2016) [30]
Kinetic spectrophotometric method	0.0027	Not established	Diluted human serum and urine samples	Linearity was established up to 0.036 μg/mL which would be too time and resource demanding for diluting permeation study samples and does not investigate interference from endogenous skin components	Keyvanfard et al. (2013) [41]
HPLC-UV	6.359	38.805	Stock solution, nasotal nasal spray	The method is not sensitive enough to detect smaller drug quantities associated with permeation studies, did not investigate skin interference	Hassib et al. (2011) [27]
Ion-paired HPLC with solid phase extraction	0.05	0.25	Human urine samples	Sensitivity seems appropriate; however, the method is time and resource intensive and does not investigate potential interference from skin	Aswania et al. (1997) [44]
HPTLC and HPLC	0.51 μg/band and 0.129	0.17 μg/band and 0.043	Drug samples in methanol, solutions of fluca eye drops or rabbit aqueous humor	Neither method evaluates overlap with endogenous biological components as rabbit aqueous humor was deproteinized before analysis, and investigation on interference from skin was not present	Hegazy et al. (2018) [32]
LC-UV	Not established	Not established	Nasal, inhaled, and ophthalmic solutions, inhaled powder	This method does not have enough evidence for sufficient selectivity or sensitivity for biological tissue/fluid analysis, did not investigate skin interference	Ng (1994) [33]
ELISA and GC/MS	<0.0006	0.009	Equine urine samples	Both methods are more time and resource demanding as ELISA assays requires sample dilution from 0.001 to 0.1 μg/mL for optimal selectivity and GC/MS requires purification, evaporation, and derivatization of samples, neither were assessed for potential skin interference	Leavitt et al. (1993) [40]
Absorptive stripping voltammetry with HMDE	Not established	Not established	Drug spiked urine, 4% CS water solutions	Authors conclude that the method is ideal for trace detection, but the method is not accurate or precise enough for analyses where CS is the primary component, did not investigate skin interference	Moreira et al. (1992) [39]
Ion-paired HPLC	≤0.25	0.25	Drug solutions with 30 : 70 acetonitrile: water diluent	Ion-paired HPLC is time consuming and costly as previously described, did not investigate skin interference	Barnes et al. (2002) [28]
HPLC-UV	92	Not established	Nasal solution	The method established is more selective and proposed for the stability indication of CS impurities rather than CS quantitation, did not investigate skin interference	Mansfield et al. (1999) [29]
HPLC-UV	0.06	0.19	Drug solutions with mobile phase	Use of the method in selectively quantifying CS from other biological compounds or skin interference was not investigated	Segall et al. (1997) [34]
HPLC-MS/MS	0.0003	0.0003	Nasal drops and spray, human plasma	Linearity established up to 0.02 μg/mL where permeation studies need to quantify higher drug contents and ESI+does not ionize CS as easily, did not investigate skin interference	Xu et al. (2008) [42]
HPLC-UV	0.05	0.05	Human urine samples with or without co-administered drugs	Method is sensitive but does not evaluate possible skin component interference and requires additional extraction and purification steps	Gardner (1984) [43]
HPTLC-UV densitometry	Not established	Not established	Drug solutions and gels, intal capsules, solutions, and gels	Linearity was validated at too small of a range for skin permeation studies and lacked analysis of skin interference	Kocic-pesic et al. (1992) [36]
HPLC-UV	Not established	Not established	Drug solutions and gels, intal capsules, solutions, and gels	Linearity was validated at too small of a range for skin permeation studies and lacked analysis of skin interference	Radulovic et al. (1994) [35]