Using a combination of synthetic fluid inclusions in halite, microvolume aqueous solutions and National Institute of Standards and Technology (NIST) Standard Reference Material (SRM) 611 Glass, calibration graphs were established for the determination of elemental ratios in natural fluid inclusions by laser ablation–inductively coupled plasma mass spectrometry (ICP-MS). For simultaneous multi-element analysis, optimization studies demonstrate the necessity to adopt a compromise set of operating conditions since ICP-MS sensitivity (signal:background) may differ from element to element as a function of argon flow, radiofrequency power and spray chamber temperature. Synthetic fluid inclusions were prepared by crystallization from saturated sodium chloride solutions containing up to 13 major and minor cations. The microvolume calibration standards, ‘microwells’, consisted of small holes (3 × 3 × 2 mm3) drilled into plastic sheet, filled with a standard solution and hermetically sealed. In order to allow direct comparison between the different test materials, all the elements (Li, Na, Mg, K, Ca, Mn, Cu, Zn, Rb, Cs, Ba, Pb, B, Cl, Br) were ratioed to strontium. The relative standard deviations for the element ratios were generally better than 25%, indicating that the nature of the sample (salt, glass and aqueous solution) does not markedly affect the consistency of ablation or the efficiency of transfer between the ablation chamber and ICP torch. Element ratios for the synthetic fluid inclusions were linear over several orders of magnitude and in close agreement with those for the NIST SRM 611 Glass and microwell solutions, irrespective of inclusion size (20–100 µm) and depth in the sample (up to 80 µm). Statistical t-tests on the mean element ratios confirm that microwells and glasses constitute suitable alternatives to synthetic fluid inclusions for the calibration and routine analysis of natural fluid inclusions.